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Meta-Analysis Identifies Optimal First-Line Chemotherapy Regimens for Advanced Pancreatic Cancer

• A comprehensive meta-analysis of 79 trials identified superior first-line chemotherapy regimens for unresectable advanced or metastatic pancreatic cancer, enhancing treatment strategies. • PAXG and gemcitabine plus nab-paclitaxel alternating with FOLFOX demonstrated the most significant improvements in overall survival compared to gemcitabine monotherapy. • NALIRIFOX and FOLFIRINOX are recommended as preferred options for patients who can tolerate them, while gemcitabine plus nab-paclitaxel remains a viable alternative. • The study highlights the need for phase 3 randomized controlled trials to further evaluate quadruplet regimens in pancreatic cancer treatment.

A recent meta-analysis published in The Lancet Oncology has identified optimal first-line chemotherapy regimens for patients with unresectable advanced or metastatic pancreatic cancer. The study, led by Lisa Salvatore, MD, PhD, from the Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, analyzed data from 79 randomized controlled phase II or III trials, encompassing a total of 22,168 patients.
The analysis, employing a Bayesian network approach, compared various chemotherapy regimens against gemcitabine monotherapy, the most frequent comparator. The primary outcomes assessed were progression-free survival and overall survival, with hazard ratios (HRs) and 95% credible intervals (CrIs) calculated to determine the efficacy of each regimen.

Key Findings in Progression-Free Survival

The network meta-analysis for progression-free survival, including 71 trials and 19,479 patients, revealed that several regimens outperformed gemcitabine monotherapy. The most effective 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)

Key Findings in Overall Survival

The network analysis for overall survival, including 79 trials and 22,104 patients, identified the following regimens as superior to gemcitabine:
  • 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)

Clinical Implications and Future Directions

According to the investigators, "Both 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 study suggests that NALIRIFOX and FOLFIRINOX should be considered the preferred options for patients who can tolerate them, while gemcitabine plus nab-paclitaxel remains a viable alternative, especially for patients unfit for triplet therapy. The authors advocate for phase 3 randomized controlled trials to investigate concomitant or sequential quadruplet regimens to further improve outcomes in advanced pancreatic cancer.
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Reference News

[1]
Performance of First-Line Chemotherapy Regimens in Unresectable Advanced or Metastatic ...
ascopost.com · Nov 20, 2024

Mastrantoni et al. identified better first-line chemotherapy regimens for unresectable advanced or metastatic pancreatic...

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