First-line systemic chemotherapy for metastatic pancreatic adenocarcinoma

HRR: homologous recombination repair; ECOG PS: Eastern Cooperative Oncology Group performance status; ULN: upper limit of normal; BRCA: breast cancer susceptibility gene; PALB2: partner and localizer of BRCA2 gene; FOLFIRINOX: leucovorin plus short-term infusional fluorouracil plus oxaliplatin and irinotecan; FOLFOX: leucovorin plus short-term infusional fluorouracil and oxaliplatin; nabpaclitaxel: nanoparticle albumin-bound paclitaxel.
* Genes associated with HRR deficiency include BRCA1/2, PALB2, ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1.
¶ In addition to ECOG PS, comorbidity, and serum bilirubin, goals of care, patient preferences, symptom burden, and psychosocial issues (including the patient's support system) should guide treatment decisions.
Δ American Society of Clinical Oncology (ASCO) guidelines defining favorable and relatively favorable comorbidity are available.^[1]
◊ Following at least 16 weeks of initial chemotherapy, nonprogressors with BRCA or PALB2 germline mutations should be offered maintenance olaparib.
§ If FOLFOX is chosen, irinotecan could be added for later cycles if mutations are discovered in an HRR-associated gene and the patient has tolerated FOLFOX adequately.
¥ Once mutational status is known, mutation carriers should be offered a platinum-containing regimen.
‡ Highly selected patients with an ECOG PS of 2 because of heavy tumor burden could be considered for gemcitabine plus nabpaclitaxel because of the higher likelihood of an objective antitumor response.