1679P - Comparison of first-line chemotherapy regimens in unresectable locally advanced or metastatic pancreatic cancer: A systematic review and network meta-analysis

Background

In patients with unresectable locally advanced (LAPC) or metastatic pancreatic cancer (MPC) gemcitabine-nab-paclitaxel (GEM-NAB) and FOLFIRINOX are standard first-line treatments. Recently, other combinations have shown to be associated with a survival advantage.

Methods

PubMed, CENTRAL, Embase and oncology meetings websites were searched to March 1^st, 2023. We included phase II and III randomized controlled trials (RCTs) enrolling patients with unresectable LAPC or MPC which investigated gemcitabine-based (GEM) regimens, FOLFIRINOX, NALIRIFOX, PAXG or other first-line combinations. Efficacy outcomes were progression-free survival (PFS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (95% CI) were computed using a random effects model. A frequentist network meta-analysis was conducted, and P-scores were used to rank treatments.

Results

4412 records were screened, and 45 studies were included; 37 studies were evaluable for PFS and 43 for OS. Considering PFS, PAXG (P-score 0.9410), NALIRIFOX (P-score 0.8723) and FOLFIRINOX (P-score 0.8696) were among the top-ranked strategies, while GEM-NAB had a P-score of 0.6388. In terms of OS, PAXG (P-score 0.9585), GEM-NAB sequential strategies (GEM-NAB > FOLFOX, P-score 0.9350 and GEM-NAB > FOLFIRI, P-score 0.9117), FOLFIRINOX (P-score 0.8512) and NALIRIFOX (P-score 0.8461) were among the top-ranked strategies, while the P-score of GEM-NAB was 0.6998. No difference was observed between NALIRIFOX and FOLFIRINOX (PFS HR: 1.01, 95% CI 0.68-1.50; OS HR: 0.99, 95% CI 0.74-1.31). A significant difference was observed between FOLFIRINOX and GEM+NAB in terms of PFS (HR 0.71, 95% CI 0.53-0.95), while a non-significant trend was observed in OS (HR 0.82, 95% CI 0.66-1.04). No difference was observed between NALIRIFOX and PAXG (PFS HR 1.25, 95% CI 0.72-2.17; OS HR 1.40, 95% CI 0.87-2.24) and between FOLFIRINOX and PAXG (PFS HR: 1.26, 95% CI 0.72-2.22; OS HR: 1.38, 95% CI 0.84-2.27).

Conclusions

With the limitations of a network meta-analysis, our results suggest that combinations with three or four drugs, when feasible, could provide a greater survival benefit compared to GEM-NAB in unresectable LAPC or MPC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.