ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد ایتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

What's new in oncology

What's new in oncology
Authors:
April F Eichler, MD, MPH
Diane MF Savarese, MD
Sadhna R Vora, MD
Sonali Shah, MD
Literature review current through: Mar 2022. | This topic last updated: Apr 22, 2022.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

BREAST CANCER

Fam-trastuzumab deruxtecan in metastatic HER2-positive breast cancer (April 2022)

Although the antibody-drug conjugate ado-trastuzumab emtansine (T-DM1) has an established role in metastatic HER2-positive breast cancer, novel antibody drug conjugates such as fam-trastuzumab deruxtecan (T-DXd) are emerging. In a randomized trial in over 500 patients with HER2-positive metastatic breast cancer with progression on a trastuzumab- and taxane-containing regimen, median progression-free survival was 25 months for T-DXd and 7.2 months for T-DM1 [1]. The estimated 12-month overall survival (OS) rates were 94 percent with T-DXd and 86 percent for T-DM1; although the difference in OS was not statistically significant, results were immature. Given these data, we now consider T-DXd an appropriate option after progression on a trastuzumab- and taxane-containing regimen. (See "Systemic treatment for HER2-positive metastatic breast cancer", section on 'Choosing between T-DM1 and T-DXd'.)

Timing of breast cancer recurrence and prognosis (March 2022)

Prognosis after recurrence of breast cancer depends on many variables, including genomic subtype and location of recurrent disease; other factors are being evaluated. In one study including over 3500 patients with breast cancer recurrence, those with a late recurrence (≥10 years from primary diagnosis) experienced a lower risk of breast cancer-associated death than those with an early recurrence (hazard ratio 0.72) [2]. These data suggest that timing of breast cancer recurrence affects prognosis and may be included among other factors in counseling patients. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Genomic subtype and timing and pattern of relapse'.)

Ribociclib in advanced breast cancer (March 2022)

The addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib to letrozole was previously shown in a randomized trial to improve progression-free survival in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, treatment-naïve, advanced breast cancer. Now, in longer follow-up of 6.6 years, the addition of ribociclib also resulted in improved overall survival (median 64 versus 51 months) [3]. Based on these and other data, we continue to recommend the addition of a CDK 4/6 inhibitor to an aromatase inhibitor as initial therapy for most patients with HR-positive, HER2-negative, advanced breast cancer, also incorporating ovarian suppression for premenopausal patients. (See "Treatment approach to metastatic hormone receptor-positive, HER2-negative breast cancer: Endocrine therapy and targeted agents", section on 'Data regarding available combinations'.)

Late breast cancer recurrence risks (March 2022)

Studies are evaluating the risks of late breast cancer recurrence among survivors. In a retrospective study, among approximately 20,000 patients who were survivors 10 years after diagnosis, the cumulative incidence of late recurrence was 9 percent at 15 years after primary diagnosis and 15 percent at 25 years [4]. High lymph node burden, large tumor size, and estrogen receptor positivity were associated with risk of late recurrence. These findings support extended adjuvant endocrine therapy in select breast cancer patients with hormone receptor-positive cancers. (See "Adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Rationale for extended treatment in some patients'.)

Carboplatin in neoadjuvant therapy for triple negative breast cancer (February 2022)

The effect of incorporation of carboplatin in neoadjuvant regimens for triple negative breast cancer (TNBC) is being evaluated. In a randomized trial, among patients with stage II to III TNBC receiving anthracycline-based chemotherapy, the addition of carboplatin increased the breast pathologic complete response rate from 46 to 60 percent but did not improve five-year event-free survival or overall survival [5]. However, the study was not powered to assess survival outcomes. In a separate trial, the addition of pembrolizumab to a carboplatin-containing chemotherapy regimen improved event-free survival (overall survival results were immature). Based on these data, our preferred regimen for patients with stage II or III TNBC includes both pembrolizumab and carboplatin. (See "Choice of neoadjuvant chemotherapy for HER2-negative breast cancer", section on 'In an anthracycline-containing regimen'.)

Cardiometabolic risk factors in breast cancer patients (February 2022)

Treatments for breast cancer can affect an individual's cardiovascular risk factors. In one study including almost 15,000 patients with newly diagnosed breast cancer and 75,000 matched controls, breast cancer patients had a higher incidence of hypertension (10.9 versus 8.9 percent) and diabetes (2.1 versus 1.7 percent) after two years, with higher diabetes incidence persisting after 10 years (9.3 versus 8.8 percent) [6]. These results may have been biased by the fact that breast cancer survivors are seen more frequently in the health care system, as part of routine surveillance. We advise routine screening for cardiometabolic issues in the primary care setting for breast cancer survivors. (See "Approach to the patient following treatment for breast cancer", section on 'Cardiometabolic issues'.)

Pembrolizumab in PD-L1-positive TNBC (January 2022)

A randomized trial (KEYNOTE-355) in patients with advanced triple-negative breast cancer (TNBC) previously demonstrated that the addition of pembrolizumab to chemotherapy modestly improved progression-free survival (PFS). Now, in preliminary reporting, pembrolizumab also improved overall survival (OS) in the subgroup with tumors expressing programmed cell death ligand 1 (PD-L1) with Combined Positive Score (CPS) ≥10 (23 versus 16 months) [7]. OS in the PD-L1-positive CPS ≥1 subgroup showed a similar trend (although not statistically significant) and PFS benefits. Given these results, we incorporate an immune checkpoint inhibitor with chemotherapy for patients with PD-L1-positive TNBC. (See "ER/PR negative, HER2-negative (triple-negative) breast cancer", section on 'PD-L1-positive tumors'.)

Aromatase inhibitors versus tamoxifen in premenopausal patients on adjuvant ovarian suppression for breast cancer (January 2022)

Ovarian function suppression (OFS) is often added to adjuvant endocrine therapy for premenopausal women with high-risk, hormone receptor (HR)-positive breast cancer, but whether it should be used with tamoxifen versus an aromatase inhibitor (AI) is unclear. In a meta-analysis of four randomized trials including 7000 premenopausal patients with HR-positive breast cancer receiving adjuvant OFS, AI improved 10-year recurrence rates versus tamoxifen (18 versus 15 percent, relative risk [RR] 0.79) [8]. Distant recurrences were also improved (RR 0.83), although breast cancer mortality rates were similar. For premenopausal patients receiving adjuvant OFS for HR-positive breast cancer, we suggest an AI, although tamoxifen is a reasonable alternative. (See "Adjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer", section on 'Rationale for AI over tamoxifen, in combination with OFS'.)

Assessing response to neoadjuvant therapy in breast cancer (January 2022)

Studies are evaluating surrogates for survival outcomes among patients with breast cancer receiving neoadjuvant chemotherapy (NACT), including pathologic complete response (pCR) rates and residual cancer burden (RCB). A meta-analysis of 54 trials of neoadjuvant therapy in over 32,000 breast cancer patients failed to confirm pCR as an adequate surrogate for disease-free survival (DFS) or overall survival (OS) [9]. A separate study demonstrated a correlation between RCB and event-free survival [10]. Although we continue to use pCR to guide adjuvant treatment decisions in patients who have received NACT, RCB can further refine prognostic information. (See "General principles of neoadjuvant management of breast cancer", section on 'Assessment for pathologic complete response'.)

IV placement, venipuncture, and blood pressure measurements after breast cancer surgery (October 2021)

Avoiding lymph node dissection is the only preventive measure proven to reduce the risk of developing lymphedema after breast cancer surgery; however, many patients are told to avoid intravenous catheters, venipunctures, and blood pressure measurements in the arm ipsilateral to the previous surgery for the rest of their lives. In agreement with the American Society of Breast Surgeons, the Society for Ambulatory Anesthesia issued a statement that these measures are not contraindicated in patients who have no lymphedema, even if they have had an axillary lymph node dissection [11]. Our approach is generally consistent with this statement. We support shared decision-making that accounts for the individual's risk factors for developing lymphedema, the clinical situation and monitoring needs, and patient preferences. (See "Breast cancer-associated lymphedema", section on 'Unsupported risk reduction strategies'.)

Adjuvant abemaciclib in high-risk, hormone receptor-positive, HER2-negative breast cancer (October 2021)

For patients with high-risk, hormone receptor (HR)-positive, HER2-negative breast cancer, previous data have shown benefits with adjuvant abemaciclib. Now, in longer follow-up of 27 months, benefits are maintained, both in regard to invasive disease-free survival (three-year rate of 89 versus 83 percent), and distant recurrence-free survival (90 versus 86 percent) [12]. A higher incidence of Grade ≥3 adverse events (AEs) was observed with versus without abemaciclib (50 versus 16 percent, respectively). These data led to US Food and Drug Administration approval of abemaciclib in patients with HR-positive, HER2-negative, node-positive breast cancer at high risk of recurrence and a Ki-67 score ≥20 percent [13], and we suggest the addition of adjuvant abemaciclib to endocrine therapy in this subset. High risk in this instance is defined as either ≥4 involved axillary lymph nodes; or 1 to 3 involved lymph nodes and either tumor grade 3 or size ≥5.0 cm. However, we note that it is also acceptable not to administer this additional treatment, given the toxicity and only short-term supporting data. (See "Adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive breast cancer", section on 'Patient selection'.)

CANCER SURVIVORSHIP

Bupropion for low sexual desire in female cancer survivors (February 2022)

Sexual dysfunction, including low sexual desire, is common among female cancer survivors, but clinical trials evaluating pharmacologic agents are limited. In a randomized trial in over 200 female survivors of breast and gynecologic cancer with low baseline sexual desire, treatment with bupropion at either 150 mg or 300 mg over a 10-week period did not improve sexual desire scores compared with placebo [14]. Our approach for female cancer survivors with low desire is to initially treat underlying physical etiologies and refer patients with persistent symptoms to a mental health and/or sexual therapist. (See "Overview of sexual dysfunction in female cancer survivors", section on 'Decreased libido and arousal'.)

ENDOCRINE TUMORS

Adjuvant therapy for low-risk adrenocortical carcinoma (March 2022)

For patients with resected adrenocortical carcinoma (ACC) at low risk for disease recurrence, the optimal approach to adjuvant therapy is not established. In a randomized clinical trial (ADIUVO) of almost 100 patients with completely resected ACC and pathologic features suggestive of low recurrence risk (stage I to III disease, complete [R0] resection, and Ki-67 expression <10 percent), the addition of adjuvant mitotane failed to demonstrate statistically significant improvements in five-year recurrence-free survival (79 versus 75 percent) and overall survival (95 versus 86 percent) compared with observation [15]. Based on these data, we suggest observation over adjuvant mitotane in most patients with completely resected ACC at low risk for disease recurrence. (See "Treatment of adrenocortical carcinoma", section on 'Patients with low recurrence risk'.)

GASTROINTESTINAL CANCER

Frontline immunotherapy in advanced esophageal squamous cell cancer (March 2022)

Two recent trials help identify which patients with advanced esophageal squamous cell cancer (SCC) are most likely to benefit from immune checkpoint inhibitor (ICI) immunotherapy. In the CheckMate 648 trial, the addition of nivolumab to chemotherapy in previously untreated, advanced unresectable, recurrent, or metastatic esophageal SCC improved survival over chemotherapy alone [16]. In the KEYNOTE-590 trial, the addition of pembrolizumab to chemotherapy improved survival in a combined population of SCC and adenocarcinoma [17]. In both trials, the benefit of an ICI was primarily seen in those with high PD-L1 expression (either tumor proportion score [TPS] ≥1 or combined positive score [CPS] ≥10). Although regulatory approval for these drugs in the United States for advanced esophageal cancer is not restricted to high PD-L1 expressing SCCs, we now suggest frontline immunotherapy plus chemotherapy only for those with TPS ≥1 or CPS ≥10. (See "Initial systemic therapy for locally advanced unresectable and metastatic esophageal and gastric cancer", section on 'Squamous cell cancers'.)

Updated ASCO guideline for adjuvant therapy in stage II colon cancer (March 2022)

Updated guidelines for adjuvant therapy in stage II colon cancer from the American Society for Clinical Oncology (ASCO) are available [18]. The guidelines recommend against routine use of adjuvant chemotherapy, especially for individuals at low risk of recurrence, reiterating the conclusion from 2004 that a significant subgroup of patients with stage II colon cancer are not expected to benefit from such therapy. Although expert groups vary in how they define high-risk stage II disease, ASCO and others recommend offering chemotherapy to patients who are at increased risk for recurrence (table 1). We suggest selecting patients for chemotherapy based on clinicopathologic risk factors and DNA mismatch-repair status (algorithm 1). (See "Adjuvant therapy for resected stage II colon cancer", section on 'Recommendations from expert groups'.)

Neoadjuvant therapy for potentially resectable and borderline resectable pancreatic cancer (February 2022)

The best approach to patients with potentially resectable or borderline resectable pancreatic cancer is not established. In updated results from the phase III PREOPANC trial, neoadjuvant therapy improved survival compared with upfront surgery followed by adjuvant therapy [19]; the difference in median overall survival was small but significant (median 15.7 versus 14.3 months), and five-year overall survival rates were substantially higher (20.5 versus 6.5 percent). A meta-analysis of seven randomized trials, including PREOPANC, also concluded that neoadjuvant therapy improved overall survival relative to upfront surgery [20]. We suggest neoadjuvant therapy rather than upfront surgery for most patients with borderline resectable pancreatic cancer. Neoadjuvant therapy is also a reasonable alternative to upfront surgery followed by adjuvant therapy in patients with potentially resectable tumors, as long as performance status and comorbidity are sufficient to tolerate treatment. (See "Treatment for potentially resectable exocrine pancreatic cancer" and "Initial chemotherapy and radiation for nonmetastatic, locally advanced, unresectable and borderline resectable, exocrine pancreatic cancer", section on 'Benefit of neoadjuvant therapy'.)

Sotorasib for KRAS G12C-mutated advanced pancreatic cancer (February 2022)

Sotorasib, a small molecule that specifically inhibits the KRAS G12C protein, is approved for treatment of KRAS G12C-mutated non-small cell lung cancer. In an updated analysis of a cohort of 38 patients with KRAS G12C-mutated metastatic pancreatic cancer receiving sotorasib on the phase I/II CodeBreak100 study, there were eight partial responses (21 percent), and the disease control rate was 84 percent [21]. Treatment was well tolerated, with grade ≥3 treatment-related adverse events in only six patients. We suggest sotorasib rather than cytotoxic chemotherapy for second-line therapy in patients with metastatic pancreatic cancer and a KRAS G12C mutation. (See "Second-line systemic therapy for advanced exocrine pancreatic cancer", section on 'RAS G12C-mutated tumors'.)

Adding immunotherapy to chemotherapy for advanced biliary tract cancer (February 2022)

For most patients with advanced unresectable biliary tract cancer, gemcitabine plus cisplatin (gem/cis) has become a standard first-line regimen. In the randomized, placebo-controlled TOPAZ-1 trial, the addition of the immune checkpoint inhibitor durvalumab to gem/cis improved overall survival (12.8 versus 11.5 months), progression-free survival, and objective response rate compared with gem/cis alone without a significant increase in treatment-related adverse effects [22]. We consider durvalumab plus gem/cis to be an alternative to gem/cis but not necessarily preferred given the added expense and the small increment in median overall survival seen in the TOPAZ-1 trial. (See "Systemic therapy for advanced cholangiocarcinoma", section on 'Gemcitabine plus cisplatin and durvalumab'.)

Hepatic intraarterial chemotherapy without embolization in unresectable hepatocellular carcinoma (November 2021)

Transarterial chemoembolization (TACE) is a standard treatment for large unresectable hepatocellular carcinomas (HCCs) that are not amenable to local thermal ablation; however, each treatment can cause hepatic arterial and parenchymal ischemic damage leading to hepatic decompensation and inability to carry out repeated procedures. In a Chinese trial comparing repeated courses of multiagent hepatic arterial infusional chemotherapy (HAIC) without embolization versus TACE in 315 patients with unresectable large (≥7 cm) HCCs without macrovascular invasion or extrahepatic spread (81 percent hepatitis B virus-related), patients treated with HAIC had improved survival and less toxicity [23]. However, the trial had important limitations, and the results may not be generalizable to other populations with HCC. Where the technical expertise is available, HAIC is an alternative to TACE for large unresectable HCCs, but we await further studies before concluding that HAIC is preferred. (See "Localized hepatocellular carcinoma: Liver-directed therapies for nonsurgical candidates not eligible for local thermal ablation", section on 'Hepatic intraarterial chemotherapy without embolization'.)

Nivolumab plus ipilimumab for initial therapy of mismatch repair deficient metastatic colorectal cancer (October 2021)

For most patients with nonoperable metastatic colorectal cancer (mCRC) that is deficient mismatch repair (dMMR) without a high tumor burden, first-line pembrolizumab is preferred over cytotoxic chemotherapy because of better efficacy and less toxicity, as shown in the KEYNOTE-177 trial. Additional data on initial immunotherapy using nivolumab and low-dose ipilimumab are available from the nonrandomized phase II CheckMate 142 trial, which demonstrated high initial response rates (62 percent) that were durable (median duration not reached with a median follow-up of 29 months) and low rates of grade 3 or 4 toxicity (22 percent) [24]. Whether these results are better than can be achieved with pembrolizumab monotherapy will require a randomized trial. Nivolumab plus low-dose ipilimumab represents an alternative but not necessarily preferred option for initial immunotherapy in dMMR mCRC. (See "Systemic therapy for nonoperable metastatic colorectal cancer: Selecting the initial therapeutic approach", section on 'Patients with deficient DNA mismatch repair/microsatellite unstable tumors'.)

GENITOURINARY ONCOLOGY

First-line therapy for high-risk, high-volume metastatic hormone-sensitive prostate cancer (April 2022)

Docetaxel plus androgen deprivation therapy (ADT) is a standard approach for initial treatment of patients with hormone-sensitive, high-risk, high-volume metastatic prostate cancer. Two trials now demonstrate an overall survival benefit from the addition of a second systemic agent to ADT plus docetaxel. In the ARASENS trial, the addition of darolutamide to ADT plus docetaxel improved overall survival and all secondary endpoints without worsening treatment-related toxicity in men with metastatic castration-sensitive prostate cancer (CSPC), and the benefits were similar in most subgroups [25]. In the PEACE-1 trial, the addition of abiraterone to ADT plus docetaxel also improved survival over ADT plus docetaxel alone in patients with de novo metastatic CSPC [26]. (See "Initial systemic therapy for advanced, recurrent, and metastatic noncastrate (castration-sensitive) prostate cancer".)

Long-term survival with maintenance avelumab in patients with advanced urothelial carcinoma (March 2022)

For patients with advanced urothelial carcinoma (UC), maintenance immunotherapy with avelumab after platinum-based chemotherapy is the standard of care, but long-term data on overall survival (OS) were previously limited. In a randomized phase III trial in 700 patients with locally advanced unresectable or metastatic UC who did not progress after initial gemcitabine plus platinum-based chemotherapy, the addition of maintenance avelumab to best supportive care (BSC) improved three-year OS (36 versus 30 percent) and was well-tolerated [27]. Based on these data, for patients with metastatic UC who do not progress on initial platinum-based chemotherapy, we recommend maintenance immunotherapy with avelumab rather than BSC alone. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Avelumab'.)

Long-term survival with nivolumab plus ipilimumab in advanced renal cell carcinoma with sarcomatoid features (March 2022)

For patients with advanced renal cell carcinoma (RCC) with sarcomatoid features, immunotherapy is more effective than vascular endothelial growth factor receptor (VEGFR) inhibitors, but long-term overall survival (OS) data were previously limited. In extended follow-up of a phase III trial in over 100 patients with treatment-naïve intermediate- or poor-risk advanced RCC with sarcomatoid features, nivolumab plus ipilimumab improved five-year OS compared with sunitinib (47 versus 21 percent) [28]. Based on these data, for patients with advanced or metastatic RCC with sarcomatoid features, we continue to recommend initial therapy with nivolumab plus ipilimumab rather than VEGFR inhibitors. (See "Renal cell carcinoma with sarcomatoid features", section on 'Nivolumab plus ipilimumab (preferred)'.)

Cemiplimab in recurrent cervical cancer (February 2022)

Immunotherapy is being evaluated in patients with recurrent cervical cancer. In a randomized trial in patients with disease progression after platinum-based chemotherapy, the checkpoint inhibitor cemiplimab improved overall survival relative to single-agent chemotherapy (12.0 months versus 8.5 months), with fewer severe toxicities [29]. Although many patients receive platinum-based chemotherapy plus pembrolizumab as initial treatment for cervical cancer, we consider cemiplimab to be an appropriate option for those with recurrent disease after platinum-based chemotherapy who did not receive a checkpoint inhibitor in the frontline setting. (See "Management of recurrent or metastatic cervical cancer", section on 'Second-line therapy'.)

Long-term follow-up of erdafitinib in advanced urothelial carcinoma (January 2022)

The gene-targeted therapy erdafitinib has regulatory approval for select patients with metastatic urothelial carcinoma (UC), but long-term follow-up was previously limited. In a phase II trial in over 100 patients with locally advanced or metastatic, treatment-refractory UC harboring alterations in FGFR2 or FGFR3, the objective response rate for erdafitinib was 40 percent at median follow-up of 24 months [30]. No new toxicity profiles were identified. Based on these results, we continue to offer erdafitinib for patients with metastatic UC and susceptible FGFR2 or 3 alterations who have progressed on both platinum-based chemotherapy and checkpoint inhibitor immunotherapy. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Erdafitinib'.)

Adjuvant pembrolizumab in localized renal cell carcinoma (December 2021)

In patients with localized renal cell carcinoma (RCC) treated with nephrectomy, adjuvant immunotherapy is being evaluated. In a randomized trial of approximately 1000 patients with clear cell RCC treated with nephrectomy, one year of adjuvant pembrolizumab improved disease-free survival (DFS) compared with placebo (two-year DFS, 77 versus 68 percent), and was well tolerated [31]. Based on these data, the US Food and Drug Administration approved adjuvant pembrolizumab in patients with RCC at intermediate-high or high risk of disease recurrence following nephrectomy [32]. We suggest adjuvant pembrolizumab for those with resected RCC who have an estimated five-year recurrence risk of ≥30 percent. (See "Overview of the treatment of renal cell carcinoma", section on 'Approach to adjuvant therapy'.)

Pembrolizumab as initial therapy for metastatic urothelial carcinoma (November 2021)

The United States (US) Food and Drug Administration (FDA) previously conditionally approved the checkpoint inhibitor pembrolizumab for patients with treatment-naïve metastatic urothelial carcinoma (UC), but long-term follow-up data were limited. In extended follow-up of a phase II trial of almost 400 patients with treatment-naïve, platinum-ineligible metastatic UC, the objective response rate for pembrolizumab was 29 percent at a median follow-up of 56 months, and three-year overall survival was 22 percent [33]. Based on these data, the US FDA granted full regulatory approval to pembrolizumab for patients with locally advanced or metastatic UC who are not eligible for any platinum-containing chemotherapy [34], and it remains one of our preferred options in this patient population. (See "Treatment of metastatic urothelial cancer of the bladder and urinary tract", section on 'Pembrolizumab'.)

Prostate cancer screening for men with germline pathogenic variants in mismatch repair genes (November 2021)

Individuals who carry germline pathogenic variants (PVs) in cancer predisposition genes involved in DNA repair (eg, BRCA2) are at risk for early-onset aggressive prostate cancer, and they may benefit from early initiation of prostate cancer screening. Interim results from the cohort of men with Lynch syndrome and germline MLH1, MSH2, and MSH6 PVs who were enrolled in the prospective IMPACT study demonstrated a higher prostate cancer incidence among men who were carriers of a germline PV in MSH6 or MSH2, but no cases were identified among carriers of an MLH1 pathogenic variant in this first screening round [35]. These findings support the use of targeted PSA screening in men with Lynch syndrome and MSH2 or MSH6 germline PVs to identify those with clinically significant prostate cancer. Additional study is needed to ascertain whether MLH1 PVs are associated with an increased risk of prostate cancer. (See "Genetic risk factors for prostate cancer", section on 'IMPACT study'.)

GYNECOLOGIC ONCOLOGY

Rucaparib for BRCA carriers with multiply-relapsed ovarian cancer (April 2022)

Inhibitors of poly(ADP-ribose) polymerase (PARP) are being evaluated in BRCA mutation carriers with relapsed advanced ovarian cancer. In an open-label randomized trial including patients who had experienced progression on two or more previous chemotherapy regimens, the PARP inhibitor rucaparib improved progression-free survival relative to further chemotherapy (7.4 versus 5.7 months) [36]. Based on these and other results, we consider PARP inhibitors to be an appropriate option in multiply-relapsed BRCA-associated ovarian cancer. (See "Management of ovarian cancer associated with BRCA and other genetic mutations", section on 'Rucaparib'.)

Serous tubal intraepithelial carcinoma at the time of risk-reducing salpingo-oophorectomy (March 2022)

For BRCA1/2 carriers who have completed childbearing, risk-reducing bilateral salpingo-oophorectomy (rrBSO) is frequently performed to reduce the risks of epithelial ovarian cancer (EOC); nevertheless, BRCA1/2 carriers remain at risk for peritoneal carcinoma, even after this procedure. In a meta-analysis of 17 studies including over 3100 BRCA1/2 carriers who underwent rrBSO, 115 were found to have serous tubal intraepithelial carcinoma (STIC) at the time of surgery; this was associated with risk for subsequent peritoneal carcinoma, with 10-year rates of 28 percent for those with STIC versus 0.9 percent for those without this finding [37]. Women found to have STIC at the time of rrBSO should be counseled regarding their risk for peritoneal cancer. (See "Cancer risks and management of BRCA1/2 carriers without cancer", section on 'Bilateral salpingo-oophorectomy'.)

Role of HPV on cervical cancer prognosis (February 2022)

In almost all cases, cervical cancer is the result of human papillomavirus (HPV) infection; however, it is unclear if HPV-positive cancer confers a better prognosis than HPV-negative cancer. In a prospective study including over 2800 patients with invasive cervical cancer, HPV-positive compared with HPV-negative cancer was associated with 43 percent relative decrease in mortality [38]. These findings are consistent with patients with head and neck cancer, in whom HPV-related disease is also associated with improved prognosis. Thus, HPV-positive disease may be used along with other factors (eg, disease stage, lymph node status) to counsel patients with cervical cancer about disease prognosis. (See "Management of early-stage cervical cancer", section on 'Prognosis'.)

Trametinib for recurrent, low-grade, serous ovarian carcinoma (February 2022)

For patients with recurrent, low-grade, serous ovarian carcinoma, there is interest in using inhibitors of the mitogen-activated protein (MAP) kinase pathway. Now, in a randomized trial among 260 patients with a mean of 2.9 previous lines of systemic therapy, the MEK inhibitor trametinib improved objective response rates (26 versus 6 percent) and progression-free survival (13.0 versus 7.2 months) compared with standard chemotherapy or endocrine therapy [39]. Overall survival was 38 versus 29 months, respectively, a difference that was not statistically significant. Although trametinib does not yet have regulatory approval for recurrent, low-grade, serous ovarian carcinoma, it is an appropriate treatment strategy for this condition and is commercially available. (See "Management of low-grade, serous carcinomas of the ovary", section on 'Recurrent or metastatic disease'.)

Lenvatinib plus pembrolizumab in advanced endometrial cancer (January 2022)

Although pembrolizumab monotherapy is used in mismatch repair-deficient advanced endometrial cancer after progression on chemotherapy, it is less effective in mismatch repair-proficient (pMMR) platinum-refractory disease. In a randomized trial in patients with advanced endometrial cancer with progression on platinum-based chemotherapy, the multiple-receptor tyrosine kinase inhibitor lenvatinib plus pembrolizumab improved both progression-free and overall survival relative to physician's choice chemotherapy in the overall group, as well as in the subset with pMMR disease [40]. For patients with pMMR advanced endometrial cancer who have recently relapsed on platinum-based chemotherapy, we suggest pembrolizumab and lenvatinib rather than further chemotherapy. (See "Treatment of metastatic endometrial cancer", section on 'Pembrolizumab plus lenvatinib'.)

HEAD AND NECK CANCER

Induction chemotherapy regimens for advanced nasopharyngeal carcinoma (April 2022)

For patients with advanced nasopharyngeal carcinoma (NPC), induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) is the standard of care, but studies directly comparing IC regimens are limited. In a phase III trial of IC with cisplatin plus paclitaxel and capecitabine (TPC) versus cisplatin plus fluorouracil in over 200 patients with locoregionally advanced NPC, TPC improved failure-free survival (84 versus 69 percent) and was well tolerated. Overall survival at three years was similar between groups (95 versus 89 percent) [41]. For patients with advanced NPC, while gemcitabine plus cisplatin continues to be our preferred IC regimen, we consider TPC to be one acceptable alternative option in this patient population. (See "Treatment of early and locoregionally advanced nasopharyngeal carcinoma", section on 'Induction chemotherapy'.)

Concurrent chemoradiation for squamous cell carcinoma of the head and neck (December 2021)

For most patients with squamous cell carcinoma of the head and neck (HNSCC), concurrent chemoradiation (CRT) is standard treatment, but overall survival (OS) data have been lacking. In longer-term follow-up of a meta-analysis including 107 randomized trials and almost 20,000 patients with locoregionally advanced HNSCC, concurrent CRT improved OS over definitive locoregional therapy (surgery and/or radiation [RT]; HR 0.83) [42]. A sustained OS benefit was only seen in those under the age of 70 years. Based on these data, for patients with locoregionally advanced HNSCC under the age of 70, we suggest concurrent CRT rather than definitive locoregional therapy. For many adults age 70 years or older, we suggest RT alone rather than CRT. (See "Locally advanced squamous cell carcinoma of the head and neck: Approaches combining chemotherapy and radiation therapy", section on 'Chemotherapy plus definitive locoregional therapy'.)

Pembrolizumab for metastatic nasopharyngeal carcinoma (November 2021)

For patients with recurrent or metastatic nasopharyngeal cancer (NPC), checkpoint inhibitor immunotherapy is an available treatment option, but it has not been directly compared against standard chemotherapy. In a randomized phase III trial of over 200 patients with recurrent or metastatic NPC previously treated with platinum-based chemotherapy [43], pembrolizumab did not improve overall survival but had lower toxicity compared with chemotherapy (gemcitabine, capecitabine, or docetaxel). Based on these data, pembrolizumab continues to be an option for patients with metastatic or recurrent NPC that is platinum-refractory, and we prefer its use in those who wish to avoid chemotherapy-related toxicity. (See "Treatment of recurrent and metastatic nasopharyngeal carcinoma", section on 'Pembrolizumab'.)

Screening for oral cavity cancer (October 2021)

Visual screening of the oral cavity (OC) is frequently used to identify squamous cell carcinoma (SCC) and can improve disease-specific survival, but studies with long-term follow-up are limited. In a randomized trial of approximately 200,000 patients in India, at up to nine years of follow-up, visual screening of the OC reduced oral SCC mortality by 27 percent in all patients and by 29 percent in ever-tobacco and/or ever-alcohol users [44]. These and other data continue to support the use of routine mouth examinations to identify and treat SCC of the OC, including individuals with high-risk exposures such as tobacco or alcohol. (See "Chemoprevention and screening in oral dysplasia and squamous cell head and neck cancer", section on 'Screening'.)

MELANOMA AND OTHER SKIN CANCER

Nivolumab plus relatlimab for advanced melanoma (April 2022)

For patients with metastatic melanoma, there is interest in identifying therapies that enhance efficacy and reduce toxicity. In a double-blind phase III trial of over 700 patients with treatment-naïve advanced melanoma, nivolumab plus relatlimab, a human immunoglobulin G4 lymphocyte activation gene 3-blocking antibody, improved progression-free survival (median 10 versus 5 months) compared to single-agent nivolumab [45,46]. Although differences in three-year overall survival were not statistically significant (56 versus 48 percent, respectively), results were immature at a median follow-up of 19 months. Grade ≥3 treatment-related adverse events occurred in 19 percent in the nivolumab-relatlimab group and 10 percent in the nivolumab group. Based on these data, the US Food and Drug Administration approved nivolumab-relatlimab for patients with unresectable or metastatic melanoma ages 12 years and older, and we consider it as one acceptable option in both BRAF wildtype and mutant disease [47]. (See "Systemic treatment of metastatic melanoma lacking a BRAF mutation", section on 'Nivolumab-relatlimab' and "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations", section on 'Nivolumab-relatlimab'.)

Tebentafusp for metastatic uveal melanoma (March 2022)

Metastatic uveal melanoma is a rare, aggressive malignancy with few effective treatment options. Tebentafusp is a bispecific T cell engager targeting glycoprotein 100, a uveal melanoma antigen. In a phase III trial in almost 400 patients with positive human leukocyte antigen (HLA)-A*02:01 and systemic treatment-naïve, advanced uveal melanoma, tebentafusp improved one-year overall survival rates compared with investigator's choice of immunotherapy or chemotherapy (73 versus 59 percent) [48]. Based on these data, the US Food and Drug Administration approved tebentafusp for adults with advanced unresectable or metastatic uveal melanoma who are HLA-1*02:01 positive [49], and we recommend its use as initial therapy in this patient population. (See "Management of metastatic uveal melanoma", section on 'HLA-A*02:01 positive (tebentafusp)'.)

Long-term follow-up of nivolumab plus ipilimumab for melanoma brain metastases (November 2021)

For patients with metastatic melanoma, immunotherapy with nivolumab plus ipilimumab is effective against central nervous system (CNS) metastases, but long-term follow-up of overall survival (OS) was previously limited. In the final analysis of a phase II trial (CheckMate-204) in over 100 patients with metastatic melanoma and asymptomatic CNS metastases treated with nivolumab plus ipilimumab, at median follow-up of 34 months, intracranial objective and complete response rates were 54 and 33 percent, respectively, and three-year OS was 72 percent [50]. Based on these and other data, nivolumab plus ipilimumab continues to be an acceptable treatment option for systemic therapy-naïve patients with metastatic melanoma and small, minimally symptomatic or asymptotic untreated CNS metastases. (See "Management of brain metastases in melanoma", section on 'Asymptomatic brain metastases'.)

Nivolumab plus ipilimumab versus targeted therapy in metastatic BRAF-mutant melanoma (January 2021)

For patients with metastatic melanoma and a BRAF mutation, treatment options include checkpoint inhibitor immunotherapy and targeted therapy with BRAF plus MEK inhibitors, but the optimal sequencing of these agents was not previously established. In a randomized phase III trial (DREAMseq) in over 250 patients with treatment-naïve BRAF mutant melanoma, initial treatment with nivolumab plus ipilimumab, followed by targeted therapy with dabrafenib plus trametinib upon disease progression, improved overall survival (OS) compared with the opposite sequencing of therapy (two-year OS 72 versus 52 percent) [51]. Based on these data, for patients with treatment-naïve metastatic melanoma and a BRAF mutation, we recommend combination immunotherapy with nivolumab plus ipilimumab rather than targeted therapy. (See "Systemic treatment of metastatic melanoma with BRAF and other molecular alterations", section on 'Choice of initial therapy'.)

NEUROONCOLOGY

Progressive parkinsonism after BCMA-targeted CAR-T cell therapy (January 2022)

Immune effector cell-associated neurotoxicity syndrome (ICANS) is a well-known acute and usually reversible complication of chimeric antigen receptor T (CAR-T) cell therapy, but long-term neurologic effects have not been well documented. A recent case report described the onset of progressive parkinsonism approximately 100 days after administration of ciltacabtagene autoleucel, an investigational CAR-T cell therapy for multiple myeloma targeting B-cell maturation antigen (BCMA) [52]. Based on postmortem studies, the syndrome appeared to be an on-target effect of CAR-T cells on BCMA-expressing astrocytes and neurons in the basal ganglia. Delayed parkinsonism has also been reported after idacabtagene vicleucel, another BCMA-targeted product. Further studies are needed to understand risk factors and treatment strategies. (See "Immune effector cell-associated neurotoxicity syndrome (ICANS)", section on 'Delayed parkinsonism'.)

Radiation fields in children >3 years with average-risk medulloblastoma (November 2021)

Results of a recent multicenter randomized trial in children with medulloblastoma support providing lower doses of radiation therapy (RT) to some areas of normal brain without sacrificing tumor control. In the Children's Oncology Group ACNS0331 trial, 549 patients age 3 to 21 years with average-risk medulloblastoma were treated with craniospinal RT plus a boost to either the entire posterior fossa (standard) or to the tumor bed only (narrower volume) [53]. Survival outcomes were similar between groups, and there were no local failures outside the narrower boost volume. Thus, use of a boost confined to the tumor bed plus a margin is now appropriate for patients receiving craniospinal RT for medulloblastoma. (See "Treatment and prognosis of medulloblastoma", section on 'Average-risk disease in children ≥3 years of age'.)

No benefit of carboplatin during radiation for high-risk medulloblastoma (November 2021)

Patients with medulloblastoma who undergo partial resection or have disseminated disease at the time of diagnosis have poor outcomes, and there has been interest in intensified treatment regimens. In the Children's Oncology Group ACNS0332 trial, nearly 300 such children age 3 to 18 years with high-risk medulloblastoma were randomly assigned to receive craniospinal radiation and weekly vincristine with or without daily carboplatin, followed by six cycles of maintenance chemotherapy [54]. With a median follow-up of nearly seven years, carboplatin did not improve event-free or overall survival, and toxicity was greater. A subgroup analysis showing possible benefit in group 3 tumors requires prospective confirmation. (See "Treatment and prognosis of medulloblastoma", section on 'High-risk disease in children ≥3 years of age'.)

Selumetinib, a MEK1/2 inhibitor, in optic pathway gliomas (November 2021)

Optic pathway gliomas (OPGs) in children often harbor BRAF alterations, and case reports have suggested that MEK1/2 or BRAF inhibitors may be an effective therapeutic approach. In a multicenter phase 2 trial that included 25 children with recurrent/progressive sporadic OPG or hypothalamic low-grade glioma treated with selumetinib, an oral MEK1/2 inhibitor, two-year progression-free survival was 74 percent, and visual acuity improved or remained stable in the majority of patients [55]. In a previously reported subset, selumetinib also showed activity in neurofibromatosis type 1 (NF1)-associated OPGs. These data add support for the use of MEK1/2 inhibitors in refractory OPGs, and randomized trials are investigating selumetinib versus chemotherapy in the upfront setting. (See "Optic pathway glioma", section on 'Role of targeted therapies'.)

SOFT TISSUE AND BONE TUMORS

Nab-sirolimus for malignant perivascular epithelioid cell differentiation (PEComa) (January 2021)

Mechanistic (mammalian) target of rapamycin (mTOR) inhibitors have shown promise for advanced perivascular epithelioid cell differentiation (PEComa). In an open-label phase II trial in approximately 30 patients with locally advanced unresectable or metastatic malignant PEComa, the mTOR inhibitor nab-sirolimus was associated with an overall response rate of 39 percent [56]. Based on these data, the US Food and Drug Administration (FDA) approved nab-sirolimus in adult patients with locally advanced unresectable or metastatic malignant PEComa. For those without access to nab-sirolimus, other mTOR inhibitors (sirolimus, everolimus, and temsirolimus) are reasonable alternatives. (See "Systemic treatment of metastatic soft tissue sarcoma", section on 'Nab-sirolimus'.)

THORACIC ONCOLOGY

Survival benefit with ALK inhibitors over chemotherapy in ALK-positive NSCLC (March 2022)

Advanced non-small cell lung cancers (NSCLC) that harbor activating ALK genetic alterations are sensitive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, which have previously shown progression-free survival benefits over chemotherapy. A meta-analysis of six trials in patients with advanced ALK-positive NSCLC found that ALK inhibitors also improved overall survival compared with chemotherapy (hazard ratio 0.84), despite substantial cross-over from chemotherapy to ALK inhibitors after the study period [57]. Moreover, ALK inhibitors increased health-related quality-of-life measures. These data reinforce our approach of using an ALK inhibitor as initial therapy for patients with advanced ALK-positive NSCLC. (See "Anaplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer", section on 'Rationale for ALK inhibitors'.)

Neoadjuvant nivolumab with chemotherapy in resectable NSCLC (March 2022)

The role of immunotherapy in the neoadjuvant management of resectable non-small cell lung cancer (NSCLC) is being evaluated. In preliminary results of Checkmate 816, among over 350 patients with resectable NSCLC and no known epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation, the addition of nivolumab to neoadjuvant platinum-doublet chemotherapy improved pathologic complete response rates (24 versus 2 percent), without impeding the completeness of surgery or increasing complications [58]. Median event-free survival rates with and without nivolumab were 31 versus 21 months. A prespecified interim analysis for overall survival resulted in a hazard ratio of 0.57; although not statistically significant, results were immature [59]. Nivolumab has been approved by the US Food and Drug Administration for use in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable NSCLCs that are ≥4 cm or node positive; we suggest its use in this setting, provided that tumors do not harbor an activating EGFR or ALK mutation [59]. (See "Systemic therapy in resectable non-small cell lung cancer", section on 'Neoadjuvant immunotherapy'.)

Dabrafenib and trametinib in BRAF-mutant NSCLC (January 2022)

The combination of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib has previously shown benefit in BRAF-mutant melanomas, but its role in non-small cell lung cancer (NSCLC) is being evaluated. In a phase II study in 93 patients with advanced NSCLC with the BRAF V600E mutation, the combination of dabrafenib plus trametinib was associated with an objective response rate of 68 percent in previously treated patients and 64 percent in treatment-naïve patients [60]. For most patients with advanced NSCLC whose tumors harbor a BRAF V600 mutation, we suggest front-line use of the combination of dabrafenib plus trametinib, rather than chemotherapy and/or immunotherapy. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer", section on 'BRAF V600E mutation'.)

Postoperative radiation therapy in resected stage III N2 NSCLC (January 2022)

Among patients with stage III N2 non-small cell lung cancer (NSCLC) who have undergone complete surgical resection, the use of postoperative radiation therapy (PORT) is controversial. In the Lung ART trial, among over 500 patients with completely resected NSCLC with pathologically proven N2 disease, those assigned to PORT versus no PORT experienced similar disease-free and overall survival [61]. However, more adverse effects were observed in the PORT group, particularly cardiopulmonary toxicity. Based on these and previous data, for patients with completely resected N2 disease, some UpToDate experts do not offer PORT, while others offer it to very select high-risk patients. (See "Management of stage III non-small cell lung cancer", section on 'Those with N2 involvement diagnosed at surgery'.)

Nivolumab in pleural mesothelioma (November 2021)

For patients with platinum-refractory pleural mesothelioma, immunotherapy has shown improvements in response rates over chemotherapy. In a randomized trial among 332 patients with platinum-refractory mesothelioma (95 percent of whom had pleural mesothelioma), those assigned to nivolumab versus placebo experienced improvements in both progression-free survival (3.0 versus 1.8 months) and overall survival (10.2 versus 6.9 months) [62]. Chemotherapy was not included as a comparator. We continue to consider either immunotherapy or single-agent chemotherapy to be appropriate options for patients with platinum-refractory pleural mesothelioma. (See "Systemic treatment for unresectable malignant pleural mesothelioma", section on 'Immunotherapy'.)

OTHER ONCOLOGY

Checkpoint inhibitors after radiation therapy in patients with cancer (April 2022)

Although checkpoint inhibitors are frequently administered after radiation therapy as systemic therapy, there are concerns about toxicity due to treatment interactions, and data are limited for the safety of this approach. In an observational study in over 16,000 patients with cancer treated with various immunotherapy regimens, the sequential use of immunotherapy within 90 days following radiation therapy was not associated with increased immune-related adverse events [63]. These data suggest that checkpoint inhibitor immunotherapy can be safely used after completion of radiation therapy to treat most malignancies. (See "Toxicities associated with checkpoint inhibitor immunotherapy", section on 'Combining or sequencing immunotherapy with other therapies'.)

Clinical efficacy of COVID-19 vaccination in cancer patients (March 2022)

Previous studies have suggested decreased seroconversion rates with COVID-19 vaccination among cancer patients versus the general population, but clinical outcomes have been unclear. In a registry study including nearly 7000 partially or fully vaccinated patients who developed COVID-19, including almost 1500 cancer patients, cancer was associated with higher risks for breakthrough infection (odds ratio [OR] 1.1) and severe outcomes (OR 1.3) compared with not having cancer, after adjustment for other clinical factors [64]. Given these and other data, we advise cancer patients to complete their vaccination series and obtain a booster vaccination, when appropriate. (See "COVID-19: Considerations in patients with cancer", section on 'Safety and efficacy'.)

ASCO offers guidance on somatic (tumor) genomic testing in patients with advanced cancer (March 2022)

The American Society of Clinical Oncology (ASCO) has issued a provisional clinical opinion that supports germline and somatic genomic testing in metastatic or advanced cancer when there are genomic biomarker-linked therapies approved by regulatory agencies for that type of cancer [65]. Given the tissue-agnostic approvals for any advanced cancer with a high tumor mutational burden or deoxyribonucleic acid (DNA) mismatch repair deficiency (checkpoint inhibitor immunotherapy), or neurotrophic tyrosine receptor kinase (NTRK) fusions (TRK inhibitors), this provides a rationale for testing for all solid tumors, if the individual would be a candidate for these treatments. For patients without an approved genomic biomarker-linked therapy, testing should be considered to determine candidacy for targeted therapies approved for other diseases; however, off-label/off-study use of such therapies is not recommended when a clinical trial is available or without evidence of meaningful efficacy in clinical trials. (See "Initial systemic chemotherapy for metastatic exocrine pancreatic cancer", section on 'Germline and targeted tumor genomic testing'.)

Additional COVID-19 vaccine primary series dose for immunocompromised individuals (August 2021, Modified February 2022)

COVID-19 vaccines are less effective among patients with certain immunocompromising conditions than in the general population; additional vaccine doses have been associated with improved effectiveness in this population. We agree with recommendations from the Advisory Committee on Immunization Practices (ACIP) in the United States that individuals with such conditions (table 2) receive an additional mRNA vaccine dose as part of their primary COVID-19 vaccine series (eg, following two doses of an mRNA vaccine or one dose of Ad26.COV2.S vaccine) (figure 1) [66,67]. This additional primary series dose is distinct from the booster dose, which such patients should additionally receive, although at a shorter interval than recommended for the general population. (See "COVID-19: Vaccines", section on 'Immunocompromised individuals'.)

Third mRNA COVID-19 vaccine dose and Omicron immunogenicity among cancer patients (January 2022, Modified January 2022)

The Omicron variant of SARS-CoV-2 partially evades vaccine-induced immunity, but for mRNA COVID-19 vaccine recipients in the general population, a third vaccine dose increases neutralizing activity against Omicron; comparable data in cancer patients are lacking. In a prospective cohort study, a third vaccine dose of the mRNA vaccine BNT162b2 was associated with a higher likelihood of detectable neutralizing activity against Omicron in patients with cancer, although the benefit was less in patients with blood cancer compared with those with solid tumors [68]. These data support administering a third dose of mRNA vaccine for patients with active cancer; such patients are also eligible subsequently for a booster dose. (See "COVID-19: Considerations in patients with cancer".)

Routine premedication for PEGylated asparaginase (January 2022)

Asparaginase, a polypeptide of bacterial origin, is an important component of treatment for acute lymphoblastic leukemia, and PEGylated products (eg, pegaspargase, calaspargase) are now preferred for newly diagnosed patients. While they are less immunogenic than nonpegylated E. coli-derived asparaginase, infusion reactions still occur in up to one-third of patients. In 2021, the pegaspargase United States prescribing information was updated to recommend routine premedication with acetaminophen, an H1-receptor blocker, and an H2-receptor blocker administered 30 to 60 minutes prior to each dose [69]. The prescribing information for calaspargase has also been similarly updated [70]. (See "Infusion reactions to systemic chemotherapy", section on 'Asparaginase'.)

Immunogenicity of available vaccines against SARS-CoV-2 in patients with cancer (January 2022)

Patients with cancer are considered to be at high risk for SARS-CoV-2 infection, but there are limited studies directly comparing available COVID-19 vaccines. In an observational cohort study (CANVAX) of over 700 patients with solid organ or hematologic cancers, two doses of an mRNA vaccine (either BNT162b2/Pfizer-BioNTech or mRNA-1273/Moderna) were associated with higher protective immune responses compared with one dose of the adenoviral vector vaccine Ad26.COV2.S/Janssen [71]. Although clinical outcomes were not measured, other studies in the general population suggest that mRNA vaccines may have greater effectiveness against severe disease. In patients with cancer receiving COVID-19 vaccination, as for the general population, we suggest an mRNA COVID vaccine, rather than an adenoviral vector vaccine. (See "COVID-19: Considerations in patients with cancer", section on 'Safety and efficacy' and "COVID-19: Vaccines", section on 'Indications and vaccine selection'.)

New naming convention for therapeutic monoclonal antibodies (January 2022)

The number of therapeutic monoclonal antibodies (mAbs) continues to increase. In order to reduce sound-alikes and specify structural components of the immunoglobulins, the World Health Organization International Nonproprietary Names (INN) Programme has introduced four new suffixes to be used instead of "mab" for antibodies developed from 2022 onward [72]. Unmodified immunoglobulins will end in "tug"; mAbs with an engineered constant region will end in "bart"; bifunctional mAbs will end in "mig"; and variable region fragments will end in "ment." (See "Overview of therapeutic monoclonal antibodies", section on 'Naming convention for therapeutic mAbs'.)

COVID-19 vaccination and hematopoietic cell transplant or CAR-T therapy (November 2021)

Immunocompromised individuals who are recipients of hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR)-T-cell therapies are at risk for a suboptimal immune response to COVID-19 vaccination. Updated guidance from the United States Centers for Disease Control and Prevention (CDC) now recommends revaccination with a full primary series for patients who were vaccinated prior to receiving HCT or CAR-T-cell therapy and who are at least three months post-HCT or CAR-T-cell therapy. Our recommendations are in agreement with this guidance [73]. (See 'COVID-19: Considerations in patients with cancer', section on 'COVID-19 vaccination' and 'Immunizations in hematopoietic cell transplant candidates and recipients', section on 'COVID-19 vaccine'.)

Comprehensive geriatric analysis in cancer patients (November 2021)

Comprehensive geriatric assessment (CGA) is being evaluated to decrease toxicity from chemotherapy in older adults. In a randomized trial among patients age ≥70 with incurable solid tumors or lymphoma starting a new systemic therapy, the CGA intervention reduced grade ≥3 adverse events compared with usual care (51 versus 71 percent) [74]. Based on these and other data, we utilize a CGA prior to initiation of anticancer therapy in patients ≥65 years. (See "Comprehensive geriatric assessment for patients with cancer", section on 'Supporting evidence'.)

REFERENCES

  1. Cortes J, Kim, S, Chung W. LBA1 - Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (Pts) with HER2+ metastatic breast cancer (mBC): Results of the randomized phase III DESTINY-Breast03 study. Ann Oncol 2021; 32S5:S1283.
  2. Pedersen RN, Mellemkjær L, Ejlertsen B, et al. Mortality After Late Breast Cancer Recurrence in Denmark. J Clin Oncol 2022; :JCO2102062.
  3. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med 2022; 386:942.
  4. Pedersen RN, Esen BÖ, Mellemkjær L, et al. The Incidence of Breast Cancer Recurrence 10-32 Years After Primary Diagnosis. J Natl Cancer Inst 2022; 114:391.
  5. Shepherd JH, Ballman K, Polley MC, et al. CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer. J Clin Oncol 2022; 40:1323.
  6. Kwan ML, Cheng RK, Iribarren C, et al. Risk of Cardiometabolic Risk Factors in Women With and Without a History of Breast Cancer: The Pathways Heart Study. J Clin Oncol 2022; :JCO2101738.
  7. Cortes J, Cescon DW, Rugo HS et. Final results of KEYNOTE-355: randomized, double-blind, phase 3 study of pembrolizumab + chemotherapy vs placebo + chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer. SABCS 2021; GS1-02.
  8. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol 2022; 23:382.
  9. Conforti F, Pala L, Sala I, et al. Evaluation of pathological complete response as surrogate endpoint in neoadjuvant randomised clinical trials of early stage breast cancer: systematic review and meta-analysis. BMJ 2021; 375:e066381.
  10. Yau C, Osdoit M, van der Noordaa M, et al. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. Lancet Oncol 2022; 23:149.
  11. Society for Ambulatory Anesthesia (SAMBA) Statement on Intravenous Catheter Placement, Venipuncture and Blood Pressure Measurements in the Ipsilateral Upper Extremity after Breast Cancer Surgery with and without Axillary Lymph Node Dissection https://samba.memberclicks.net/assets/docs/SAMBA_Statements/SAMBA_Statement_IV-Breast-Surg.pdf (Accessed on October 19, 2021).
  12. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol 2021; 32:1571.
  13. Abemaciclib tablets. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf (Accessed on October 15, 2021).
  14. Barton DL, Pugh SL, Ganz PA, et al. Randomized Controlled Phase II Evaluation of Two Dose Levels of Bupropion Versus Placebo for Sexual Desire in Female Cancer Survivors: NRG-CC004. J Clin Oncol 2022; 40:324.
  15. Berruti A, Fassnacht M, Libe R, et al. First randomized trial on adjuvant mitotane in adrenocortical carcinoma patients: The Adjuvo study. J Clin Oncol 2022; 40;6S.
  16. Doki Y, Ajani JA, Kato K, et al. Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 2022; 386:449.
  17. Shitara K, Janjigian YY, Moehler MH, et al. , Nivolumab (NIVO) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer/esophageal adenocarcinoma (GC/GEJC/EAC): Expanded efficacy, safety, and subgroup analyses from CheckMate 649 (abstract). J Clin Oncol 2022.40.4_suppl.240. Abstract available online at https://meetinglibrary.asco.org/record/204510/abstract (Accessed on February 15, 2022).
  18. Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update. J Clin Oncol 2022; 40:892.
  19. Versteijne E, van Dam JL, Suker M, et al. Neoadjuvant Chemoradiotherapy Versus Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Long-Term Results of the Dutch Randomized PREOPANC Trial. J Clin Oncol 2022; 40:1220.
  20. van Dam JL, Janssen QP, Besselink MG, et al. Neoadjuvant therapy or upfront surgery for resectable and borderline resectable pancreatic cancer: A meta-analysis of randomised controlled trials. Eur J Cancer 2022; 160:140.
  21. Strickler JH, et al. First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: A phase I/II study evaluating efficacy and safety (ASCO virtual plenary session abstract 360490). Abstract available online at https://ascopubs.org/doi/10.1200/JCO.2022.40.36_suppl.360490 (Accessed on February 22, 2022).
  22. Oh D-Y, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1 (abstract). J Clin Oncol 2022.40.4_suppl.378. Abstracat available online at https://meetinglibrary.asco.org/record/204876/abstract (Accessed on February 03, 2022).
  23. Li QJ, He MK, Chen HW, et al. Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin Versus Transarterial Chemoembolization for Large Hepatocellular Carcinoma: A Randomized Phase III Trial. J Clin Oncol 2022; 40:150.
  24. Lenz HJ, Van Cutsem E, Luisa Limon M, et al. First-Line Nivolumab Plus Low-Dose Ipilimumab for Microsatellite Instability-High/Mismatch Repair-Deficient Metastatic Colorectal Cancer: The Phase II CheckMate 142 Study. J Clin Oncol 2022; 40:161.
  25. Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med 2022; 386:1132.
  26. Fizazi K, Foulon S, Carles J, et al.. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel. Lancet 2022.
  27. Powles T, Park SH, Voog E, et al. Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Long-term follow-up results from the JAVELIN Bladder 100 trial. J Clin Oncol 2022; 40;6S.
  28. Tannir NM, Signoretti S, Choueiri TK, et al. Efficacy and safety of nivolumab plus ipilimumab (N+I) versus sunitinib (S) for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5-year minimum follow-up. J Clin Oncol 2022; 40;6S.
  29. Tewari KS, Monk BJ, Vergote I, et al. Survival with Cemiplimab in Recurrent Cervical Cancer. N Engl J Med 2022; 386:544.
  30. Siefker-Radtke AO, Necchi A, Park SH, et al. Efficacy and safety of erdafitinib in patients with locally advanced or metastatic urothelial carcinoma: long-term follow-up of a phase 2 study. Lancet Oncol 2022; 23:248.
  31. Choueiri TK, Tomczak P, Park SH, et al. Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma. N Engl J Med 2021; 385:683.
  32. Pembrolizumab: United States (US) Food and Drug Administration (FDA) Label https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s113lbl.pdf (Accessed on November 19, 2021).
  33. O'Donnell PH, Balar AJ, Vuky J, et al. First-line pembrolizumab (pembro) in cisplatin-ineligible patients with advanced urothelial cancer (UC): Response and survival results up to five years from the KEYNOTE-052 phase 2 study. J Clin Oncol 2021; 39;15S.
  34. Pembrolizumab: United States Food and Drug Administration Prescribing Label https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s117,s118lbl.pdf (Accessed on September 07, 2021).
  35. Bancroft EK, Page EC, Brook MN, et al. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study. Lancet Oncol 2021; 22:1618.
  36. Kristeleit R, Lisyanskaya A, Fedenko A, et al. Rucaparib versus standard-of-care chemotherapy in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation (ARIEL4): an international, open-label, randomised, phase 3 trial. Lancet Oncol 2022; 23:465.
  37. Steenbeek MP, van Bommel MHD, Bulten J, et al. Risk of Peritoneal Carcinomatosis After Risk-Reducing Salpingo-Oophorectomy: A Systematic Review and Individual Patient Data Meta-Analysis. J Clin Oncol 2022; :JCO2102016.
  38. Lei J, Arroyo-Mühr LS, Lagheden C, et al. Human Papillomavirus Infection Determines Prognosis in Cervical Cancer. J Clin Oncol 2022; :JCO2101930.
  39. Gershenson DM, Miller A, Brady WE, et al. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial. Lancet 2022; 399:541.
  40. Makker V, Colombo N, Casado Herráez A, et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer. N Engl J Med 2022; 386:437.
  41. Li WZ, Lv X, Hu D, et al. Effect of Induction Chemotherapy With Paclitaxel, Cisplatin, and Capecitabine vs Cisplatin and Fluorouracil on Failure-Free Survival for Patients With Stage IVA to IVB Nasopharyngeal Carcinoma: A Multicenter Phase 3 Randomized Clinical Trial. JAMA Oncol 2022.
  42. Lacas B, Carmel A, Landais C, et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group. Radiother Oncol 2021; 156:281.
  43. Chan ATC, Lee VHF, Hong R, et al. Results of KEYNOTE-122: A phase III study of pembrolizumab (pembro) monotherapy vs chemotherapy (chemo) for platinum-pretreated, recurrent or metastatic (R/M) nasopharyngeal carcinoma (NPC). Ann Oncol 2021; 32;5S.
  44. Cheung LC, Ramadas K, Muwonge R, et al. Risk-Based Selection of Individuals for Oral Cancer Screening. J Clin Oncol 2021; 39:663.
  45. Tawbi HA, Schadendorf D, Lipson EJ, et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med 2022; 386:24.
  46. Long GV, Hodi S, Lipson EJ, Schadendorf D. Ascierto. Relatlimab and nivolumab versus nivolumab in previously untreated metastatic or unresectable melanoma: Overall survival and response rates from RELATIVITY-047 (CA224-047). J Clin Oncol 2022; 40;36S.
  47. Nivolumab-relatlimab: US Food and Drug Administration Label and Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761234s000lbl.pdf (Accessed on March 21, 2022).
  48. Nathan P, Hassel JC, Rutkowski P, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med 2021; 385:1196.
  49. Tebentafusp: US Food and Drug Administration Prescribing Label https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf (Accessed on January 31, 2022).
  50. Tawbi HA, Forsyth PA, Hodi FS, et al. Long-term outcomes of patients with active melanoma brain metastases treated with combination nivolumab plus ipilimumab (CheckMate 204): final results of an open-label, multicentre, phase 2 study. Lancet Oncol 2021; 22:1692.
  51. Atkins MB, Lee SJ, Chmielowski B, et al. DREAMseq (Doublet, Randomized Evaluation in Advanced Melanoma Sequencing): A phase III trial—ECOG-ACRIN EA6134. J Clin Oncol 2021; 36S.
  52. Van Oekelen O, Aleman A, Upadhyaya B, et al. Neurocognitive and hypokinetic movement disorder with features of parkinsonism after BCMA-targeting CAR-T cell therapy. Nat Med 2021; 27:2099.
  53. Michalski JM, Janss AJ, Vezina LG, et al. Children's Oncology Group Phase III Trial of Reduced-Dose and Reduced-Volume Radiotherapy With Chemotherapy for Newly Diagnosed Average-Risk Medulloblastoma. J Clin Oncol 2021; 39:2685.
  54. Leary SES, Packer RJ, Li Y, et al. Efficacy of Carboplatin and Isotretinoin in Children With High-risk Medulloblastoma: A Randomized Clinical Trial From the Children's Oncology Group. JAMA Oncol 2021; 7:1313.
  55. Fangusaro J, Onar-Thomas A, Poussaint TY, et al. A phase II trial of selumetinib in children with recurrent optic pathway and hypothalamic low-grade glioma without NF1: a Pediatric Brain Tumor Consortium study. Neuro Oncol 2021; 23:1777.
  56. Wagner AJ, Ravi V, Riedel RF, et al. Long-term follow-up for duration of response (DoR) after weekly nab-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): Results from a registrational open-label phase II trial, AMPECT. J Clin Oncol 2020; 38S.
  57. Cameron LB, Hitchen N, Chandran E, et al. Targeted therapy for advanced anaplastic lymphoma kinase (<I>ALK</I>)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev 2022; 1:CD013453.
  58. Spicer J, Wang C, Tanaka F, et al. Surgical outcomes from the phase 3 CheckMate 816 trial: Nivolumab plus platinum-doublet chemotherapy (chemo) versus chemo alone as neoadjuvant treatment for patients with resectable non-small cell lung cancer. J Clin Oncol 2021; 39S: ASCO #8503.
  59. Nivolumab injection. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/225554s112lbl.pdf (Accessed on March 07, 2022).
  60. Planchard D, Besse B, Groen HJM, et al. Phase 2 Study of Dabrafenib Plus Trametinib in Patients With BRAF V600E-Mutant Metastatic NSCLC: Updated 5-Year Survival Rates and Genomic Analysis. J Thorac Oncol 2022; 17:103.
  61. Le Pechoux C, Pourel N, Barlesi F, et al. Postoperative radiotherapy versus no postoperative radiotherapy in patients with completely resected non-small-cell lung cancer and proven mediastinal N2 involvement (Lung ART): an open-label, randomised, phase 3 trial. Lancet Oncol 2022; 23:104.
  62. Fennell DA, Ewings S, Ottensmeier C, et al. Nivolumab versus placebo in patients with relapsed malignant mesothelioma (CONFIRM): a multicentre, double-blind, randomised, phase 3 trial. Lancet Oncol 2021; 22:1530.
  63. Anscher MS, Arora S, Weinstock C, et al. Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy: A Pooled Analysis of Trials in the US Food and Drug Administration Database. JAMA Oncol 2022; 8:232.
  64. Song Q, Bates B, Shao YR, et al. Risk and Outcome of Breakthrough COVID-19 Infections in Vaccinated Patients With Cancer: Real-World Evidence From the National COVID Cohort Collaborative. J Clin Oncol 2022; :JCO2102419.
  65. Chakravarty D, Johnson A, Sklar J, et al. Somatic Genomic Testing in Patients With Metastatic or Advanced Cancer: ASCO Provisional Clinical Opinion. J Clin Oncol 2022; 40:1231.
  66. CDC - An Additional Dose of mRNA COVID-19 Vaccine Following a Primary Series in Immunocompromised People. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-08-13/02-COVID-Dooling-508.pdf (Accessed on August 14, 2021).
  67. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (Accessed on February 24, 2022).
  68. Fendler A, Shepherd S, Au L, et al. Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer. Lancet 2022.
  69. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/103411s5201lbl.pdf (Accessed on January 04, 2022).
  70. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761102s008lbl.pdf (Accessed on January 04, 2022).
  71. Naranbhai V, Pernat CA, Gavralidis A, et al. Immunogenicity and Reactogenicity of SARS-CoV-2 Vaccines in Patients With Cancer: The CANVAX Cohort Study. J Clin Oncol 2022; 40:12.
  72. Balocco R, De Sousa Guimaraes Koch S, Thorpe R, et al. New INN nomenclature for monoclonal antibodies. Lancet 2022; 399:24.
  73. Interim Clinical Considerations for Use of COVID-19 Vaccines Currently Authorized in the United States. https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html (Accessed on November 04, 2021).
  74. Mohile SG, Mohamed MR, Xu H, et al. Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study. Lancet 2021.
Topic 8361 Version 11100.0

References