Pembrolizumab monotherapy*^[1]

Cycle length: Every three weeks, OR every six weeks. Duration of therapy: Until disease progression or unacceptable toxicity.
Drug	Dose and route	Administration	Given on days
Pembrolizumab	200 mg IV	Dilute in NS or D5W^¶ to a final concentration between 1 and 10 mg/mL and infuse over 30 minutes through an 0.2- to 5-micron sterile, nonpyrogenic, low-protein-binding inline or add-on filter.	Day 1, every three weeks
OR
Pembrolizumab	400 mg IV	Dilute in NS or D5W^¶ to a final concentration between 1 and 10 mg/mL and infuse over 30 minutes through a 0.2- to 5-micron sterile, nonpyrogenic, low-protein-binding inline or add-on filter.	Day 1, every six weeks
Pretreatment considerations:
Immune status	Anti-PD-1 monoclonal antibodies generate an immune response that may aggravate underlying autoimmune disorders or prior immune-related adverse events. There are only limited data on the safety and efficacy of checkpoint inhibitors such as pembrolizumab in patients with an underlying autoimmune disorder.^[2] Pembrolizumab should be used with extreme caution in such individuals.
Emesis risk	Minimal. Refer to UpToDate topics on prevention of chemotherapy-induced nausea and vomiting in adults.
Prophylaxis for infusion reactions	There is no standard premedication regimen for pembrolizumab.
Infection prophylaxis	Primary prophylaxis with G-CSF is not indicated (estimated risk of febrile neutropenia is <5%).
Dose adjustment for baseline liver or renal dysfunction	None required.
Thyroid function tests	Assess baseline thyroid function tests (TSH, FT4) prior to initiation of therapy.
Regulatory issues	An FDA-approved patient medication guide, which is available with the United States Prescribing Information,^[1] must be dispensed with this medication.
Monitoring parameters:
CBC with differential and platelet count every three weeks prior to each new cycle of treatment.
Assess electrolytes (including glucose) and liver and renal function tests every three weeks prior to each new cycle of treatment. Assess thyroid function tests prior to initiation of therapy and every one to two cycles during treatment, and/or as clinically indicated.
Monitor for fatigue, colitis, hepatotoxicity, hypophysitis, adrenal insufficiency, hypo- or hyperthyroidism, nephrotoxicity, pneumonitis, hyperglycemia, and skin rash. Many other clinically relevant immune-mediated toxicities have been observed, which may involve any organ system or tissue, and may be severe or fatal.
Monitor for infusion reactions during treatment. Interrupt infusion and permanently discontinue for severe or life-threatening infusion-related reactions, as indicated in the United States Prescribing Information.^[1]
While immune-mediated toxicities generally occur during treatment with pembrolizumab, adverse reactions, including infusion-related reactions, may also develop weeks to months after therapy discontinuation. Refer to UpToDate topics on toxicities associated with checkpoint inhibitor immunotherapy.
Suggested dose modifications for toxicity:
All patients should be closely monitored and evaluated for immune-mediated adverse effects at least every three weeks during therapy.
No dosage reductions of pembrolizumab are recommended; treatment is withheld or discontinued to manage toxicities.
In general, if an immune-mediated adverse event is suspected, evaluate appropriately to confirm or exclude other causes. Based on the type and severity of the reaction, withhold treatment and administer systemic glucocorticoids. Upon resolution to ≤grade 1, initiate glucocorticoid taper. Immune-mediated adverse reactions that do not resolve with systemic glucocorticoids may be managed with other systemic immunosuppressants (based on limited data). Discontinue pembrolizumab permanently for any grade 4 or recurrent grade 3 immune-mediated adverse event or one that is life threatening, grade 3 pneumonitis, AST/ALT elevation >8 times ULN, total bilirubin elevation >3 times ULN in patients with no hepatic tumor involvement, AST/ALT elevation to >10 times ULN for hepatitis with hepatic tumor involvement, grade ≥2 myocarditis, grade 3 neurologic toxicity, suspected exfoliative dermatologic condition, severe (grade 3) or life-threatening (grade 4) infusion reactions, or if there is an inability to reduce glucocorticoid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating glucocorticoids.^[1]
Most pembrolizumab-associated rashes can be managed with topical corticosteroid creams.
Guidelines for managing specific toxicities, including immune-mediated adverse events, are available in the United States Prescribing Information for pembrolizumab,^[1] from ASCO,^[3] from the MASCC,^[4] from the NCCN,^[5] and from the SITC.^[6] Refer to UpToDate topics on toxicities associated with checkpoint inhibitor immunotherapy.

This table is provided as an example of how to administer this regimen; there may be other acceptable methods. This regimen must be administered by a clinician trained in the use of antineoplastic therapy, who should use independent medical judgment in the context of individual circumstances to make adjustments, as necessary.

IV: intravenous; NS: normal saline; D5W: 5% dextrose in water; PD-1: programmed cell death protein 1; G-CSF: granulocyte-colony stimulating factors; TSH: thyroid-stimulating hormone; FT4: free thyroxine; FDA: US Food and Drug Administration; CBC: complete blood count; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ULN: upper limit of normal; ASCO: American Society of Clinical Oncology; MASCC: Multinational Association of Supportive Care in Cancer; NCCN: National Comprehensive Cancer Network; SITC: Society for Immunotherapy of Cancer; PD-L1: programmed cell death ligand 1; MMR: DNA mismatch repair.

* Single-agent pembrolizumab may be used for a variety of malignancies, including advanced cervical, head and neck squamous cell, hepatocellular, kidney, urothelial, esophagogastric (PD-L1 overexpressing), non-small cell lung, small cell lung, and Merkel cell cancers; primary mediastinal B cell lymphoma; Hodgkin lymphoma; melanoma; and microsatellite unstable (MMR-deficient) advanced cancer.

¶ Diluent solutions should not be modified without consulting a detailed reference due to potential incompatibility(ies).

References:

Pembrolizumab. United States Prescribing Information. US National Library of Medicine. (Available online at dailymed.nlm.nih.gov, accessed on September 12, 2019).
Pantuck M, et al. Cancer 2019; 125:3506.
Schneider BJ, et al. J Clin Oncol 2021.
MASCC 2020 clinical practice recommendations for the management of immune-mediated adverse events from checkpoint inhibitors. (Available online at link.springer.com/journal/520/topicalCollection/AC_c9dc4afd8c5d6799b830394e9758cad9, accessed on January 26, 2021).
NCCN guidelines for management of immunotherapy-related toxicities. (Available online at nccn.org, accessed on June 21, 2021).
SITC cancer immunotherapy guidelines. (Available online at sitcancer.org/research/cancer-immunotherapy-guidelines, accessed on March 10, 2022).

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خرید پکیج

Pembrolizumab monotherapy*[1]

Pembrolizumab monotherapy*^[1]