NALIRIFOX vs FOLFIRINOX vs gemcitabine plus nab-paclitaxel as first-line treatment of advanced pancreatic cancer: An individual patient data pooled analysis of phase 3 registration trials

e16262 Background: The NAPOLI-3 trial showed the superiority of the NALIRIFOX regimen over the combination of gemcitabine and nab-Paclitaxel (GemNabP) as first-line treatment (1LTx) of advanced pancreatic cancer (PDAC), thus being candidate as a reference regimen in this setting. However, a comparison with the FOLFIRINOX regimen has not yet been performed. Methods: We performed a pooled analysis of phase III trials that defined FOLFIRINOX, NALIRIFOX and GemNabP as optimal 1LTx options in advanced PDAC. Individual patient outcomes were retrieved from Kaplan Meier plots of each trial, and analysed after assessment of data reconstruction accuracy. Progression free survival (PFS) and overall survival (OS) were compared between the three different arms, using Cox proportional hazard models including each trial as a random effect variable to account for inter-trial variability. Overall response rates (ORR) and Grade 3 or 4 (G3/4) toxicity rates were also compared. Results: A total of 1372 patients treated with FOLFIRINOX (n=171, 12), NALIRIFOX (n=383, 28) and GemNabP (n=818, 60) were included. Median PFS was significantly longer in patients treated with NALIRIFOX (7.4 months) as compared to FOLFIRINOX [6.4 months, HR 1.48 (95% CI 1.21 - 1.82), p<.001] and GemNabP [5.6 months, HR 1.45 (95% CI 1.24 - 1.70), p = p<.001]. NALIRIFOX also provided significantly higher ORR [42% vs 32% (FOLFIRINOX) vs 29% (GemNabP), p<.001]. GemNabP was associated with poorer OS [9.2 months, HR 1.25 (95% CI 1.07 - 1.46), p=0.005], while no significant difference was observed between FOLFIRINOX [11.1 months, HR 1.12, (95% CI 0.88 - 1.43), p=0.344] and NALIRIFOX (11.1 months). Among G3/4 events, NALIRIFOX was associated with higher rates of diarrhea [p<.001] and lower rates of peripheral neuropathy, thrombocytopenia and neutropenia [p<.001], though with no difference in febrile neutropenia occurrence [p=0.158]. Conclusions: NALIRIFOX may provide superior ORR and PFS as compared to FOLFIRINOX and GemNabP as 1LTx of advanced PDAC, though with higher gastrointestinal toxicities and no difference in OS compared to FOLFIRINOX. Careful patient selection, drug costs consideration and direct comparison between FOLFIRINOX and NALIRIFOX is warranted. [Table: see text]