Pancreatic Adenocarcinoma: Treatment by Stage

Pancreatic Adenocarcinoma: Treatment by Stage: overview

This algorithm organizes treatment of pancreatic adenocarcinoma by disease extent, performance status, biomarkers and line of therapy. For resectable or borderline disease, the chart shows surgery followed by adjuvant mFOLFIRINOX (PRODIGE-24), with gemcitabine plus capecitabine as the alternative (ESPAC-4). For metastatic disease with good performance status, first-line options are the triplet FOLFIRINOX (PRODIGE 4/ACCORD 11), the doublet gemcitabine plus nab-paclitaxel (MPACT) and the triplet NALIRIFOX (NAPOLI-3). In the site's NAPOLI-3 summary, NALIRIFOX improved OS and PFS over nab-paclitaxel plus gemcitabine (OS 11.1 vs 9.2 months, HR 0.83). Patients with poor performance status are directed to gemcitabine with or without nab-paclitaxel, or to best supportive care.

Biomarker-directed branches include platinum followed by maintenance olaparib for germline BRCA mutations (POLO) and pembrolizumab for MSI-H, dMMR or TMB-high tumors (KEYNOTE-158). After gemcitabine-based therapy, second-line options are liposomal irinotecan plus 5-FU/LV (NAPOLI-1), or FOLFOX or FOLFIRI if not used previously.

Trials behind this algorithm

PRODIGE 24 Conroy T et al, NEJM, 2018; PMID: 30575490
ESPAC-4 Neoptolemos JP et al, Lancet, 2017; PMID: 28129987
MPACT Von Hoff DD et al, N Engl J Med, 2013; PMID: 24131140
NAPOLI-3 Wainberg ZA et al, Lancet, 2023; PMID: 37708904
POLO Trial Golan T et al, NEJM, 2019, PMID 31157963
KEYNOTE-158 Marabelle A et al, Lancet Oncol, 2020; PMID: 32919526

Background reading: Pancreatic cancer board review notes.

Pancreatic Adenocarcinoma: Treatment by Stage: the algorithm in words

Starting point: Pancreatic adenocarcinoma. Full background: Pancreatic cancer notes.

Resectable / borderline (first-line): Adjuvant: Surgery → adjuvant mFOLFIRINOX (PRODIGE-24); Alternative: Gemcitabine + capecitabine (ESPAC-4).
Metastatic · good PS (first-line): Triplet: FOLFIRINOX (PRODIGE 4/ACCORD 11); Doublet: Gemcitabine + nab-paclitaxel (MPACT); Triplet: NALIRIFOX (NAPOLI-3).
Metastatic · poor PS (first-line): Gentler: Gemcitabine ± nab-paclitaxel (MPACT); Supportive: Best supportive care (symptom-directed).
Biomarker-directed (first-line): gBRCA: Platinum → maintenance olaparib (POLO); MSI-H: Pembrolizumab (dMMR / TMB-high).
Second-line (post-gem) (second-line): Cytotoxic: Liposomal irinotecan + 5-FU/LV (NAPOLI-1); Cytotoxic: FOLFOX / FOLFIRI (if not used).