In a meta-analysis reported in The Lancet Oncology, Mastrantoni et al identified first-line chemotherapy regimens associated with better outcomes in patients with unresectable advanced or metastatic pancreatic cancer.
Study Details
The Bayesian network analysis included 79 randomized controlled phase II or III trials with a total of 22,168 patients published after January 1, 2000. Gemcitabine was the most frequent comparator—used in 50 of 79 trials (63%)—and was considered as the reference treatment. The primary outcome measures were progression-free and overall survival. Hazard ratios (HRs) with 95% credible intervals (CrIs) were estimated using a Bayesian approach.
Key Findings
The network meta-analysis for progression-free survival included 71 trials, 65 regimens, and 19,479 patients. Compared with gemcitabine monotherapy, the best regimens were:
- Gemcitabine plus nab-paclitaxel alternating with leucovorin, fluorouracil, and oxaliplatin (FOLFOX; HR = 0.32, 95% CrI = 0.22–0.47)
- Cisplatin, nab-paclitaxel, capecitabine, and gemcitabine (PAXG; HR = 0.35, 95% CrI = 0.22–0.55)
- Liposomal irinotecan combined with fluorouracil, leucovorin, and oxaliplatin (NALIRIFOX; HR = 0.43, 95% CrI = 0.34–0.54)
- Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX; HR = 0.55, 95% CrI = 0.47–0.65)
- Gemcitabine plus nab-paclitaxel (HR = 0.62, 95% CrI = 0.54–0.72).
The network analysis for overall survival included 79 trials, 72 regimens, and 22,104 patients. Compared with gemcitabine, the best regimens were:
- PAXG (HR = 0.40, 95% CrI = 0.25–0.65)
- Gemcitabine plus nab-paclitaxel alternating with FOLFOX (HR = 0.46, 95% CrI = 0.32–0.66)
- NALIRIFOX (HR = 0.56, 95% CrI = 0.45–0.70)
- FOLFIRINOX (HR = 0.66, 95% CrI = 0.56–0.78)
- Gemcitabine plus nab-paclitaxel (HR = 0.67, 95% CrI = 0.59–0.77).
“[B]oth PAXG and gemcitabine plus nab-paclitaxel alternating with FOLFOX were evaluated only in phase 2 trials and warrant assessment in phase 3 randomised clinical trials,” the investigators stated.
The investigators concluded: “Our findings suggest that NALIRIFOX and FOLFIRINOX should be the preferred options for patients who can tolerate these regimens, with gemcitabine plus nab-paclitaxel remaining a viable alternative, particularly in patients unfit for triplet therapy. Phase 3 randomised controlled trials investigating concomitant or sequential quadruplets are warranted.”
Lisa Salvatore, MD, PhD, of the Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, is the corresponding author of The Lancet Oncology article.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
