Version July 2025
BRCA: breast cancer susceptibility gene; CA-19-9: carbohydrate antigen 19-9 or cancer antigen 19-9; CHF: congestive heart failure; COPD: chronic obstructive pulmonary disease; CrCl: creatinine clearance; CT: computed tomography; ECOG: Eastern Cooperative Oncology Group; FOLFIRINOX: fluorouracil, leucovorin, oxaliplatin and irinotecan; FOLFOX: fluorouracil, leucovorin, and oxaliplatin; FU: fluorouracil; HRD: homologous repair deficiency; INR: international normalized ratio; LV: leucovorin; nabpaclitaxel: nanoparticle albumin-bound paclitaxel; NALIFIROX: liposomal irinotecan, fluorouracil, leucovorin, and oxaliplatin; PALB2: partner and localizer of BRCA2 gene; PARP: poly-ADP ribose polymerase; PS: performance status; ULN: upper limit of normal.
* Patients with hyperbilirubinemia due to tumor obstruction should be evaluated for endoscopic or surgical interventions to decompress the biliary tract prior to initiating systemic therapy.
¶ All patients with metastatic exocrine pancreatic cancer should receive universal germline testing to assess for associated genetic conditions as well as somatic (tumor) tissue testing for actionable molecular alterations. We do not delay initiation of systemic therapy while awaiting pending genetic test results, given the aggressive nature of this disease. Patients awaiting the results of genetic testing (or those whose results are unknown) are initially managed similar to those without actionable molecular alterations. Those whose test results reveal an actionable mutation may switch to the appropriate therapy if necessary.
Δ Patients should have appropriate PS and a good comorbidity profile to receive chemotherapy (refer to inset). Patients who do not meet these criteria should be evaluated for alternate therapies or receive best supportive care.
◊ Patients with BRCA1/2 or PALB2 mutations who do not progress after at least four months of platinum-based therapy are candidates for maintenance therapy with PARP inhibitors.
§ Pathogenic variants (either germline or somatic) in non-core HRD genes (those other than BRCA1/2 and PALB2) are associated with improved sensitivity to platinum-based chemotherapy. These include ATM, BAP1, BARD1, BLM, BRIP1, CHEK2, FAM175A, FANCA, FANCC, NBN, RAD50, RAD51, RAD51C, and RTEL1.
¥ These treatment options are appropriate for patients who are ineligible for or decline chemotherapy.
‡ Single-agent chemotherapy (eg, gemcitabine, infusional fluorouracil plus leucovorin, or capecitabine) is appropriate for some patients willing to undergo the risks of adverse effects, despite low objective response rates.
† Patients with mild to moderate elevations in serum total bilirubin >1.5 times ULN must otherwise meet all other criteria to receive chemotherapy (refer to inset). Those who do not meet these criteria may be evaluated for alternate therapies or receive best supportive care.