PAXG versus (m)FOLFIRINOX as first-Line therapy for unresectable locally advanced or metastatic pancreatic cancer: A real-world, propensity-weighted analysis.

Abstract

e16401 Background: The PACT-21 (CASSANDRA) study recently demonstrated an event-free survival benefit with PAXG (cisplatin, nab-paclitaxel, capecitabine and gemcitabine) over modified FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin) as neoadjuvant regimen in patients (pts) with early-stage pancreatic cancer (PDAC). A head-to-head comparison between these two intensive regimens in pts with unresectable, locally advanced (LAPC) or metastatic (m) PDAC has not yet been reported. Methods: We performed a retrospective analysis comparing consecutive pts with LAPC/mPDAC treated with FOLFIRINOX (or mFOLFIRINOX) or PAXG as first-line therapy between 2020 - 2024 at the Veneto Institute of Oncology (IOV), Padua, Italy. The primary endpoints were progression free survival (PFS) and overall survival (OS), as evaluated from the start of first line, according to the chosen regimen. To account for selection bias, clinical differences between the treatment arms were balanced through inverse probability of treatment weighting (IPTW). Results: A total of 138 patients were included, of whom 62 (45%) treated with mFOLFIRINOX and 76 (55%) with PAXG. Baseline characteristics [age, ECOG performance status, BMI, stage (LAPC vs mPDAC) and Ca19-9 levels] were balanced between the two arms after IPTW (n= 101, Table 1). No significant difference was observed in PFS [median 5.5 (mFOLFIRINOX) vs 7.6 (PAXG) months, adjusted HR 1.02, 95%CI 0.67 - 1.8, p = 0.71) or OS (median 16.0 vs. 12.0 months, adjusted HR 1.12, 95%CI 0.28 - 2.27, p = 0.24). Conclusions: In this real-world cohort, mFOLFIRINOX and PAXG showed comparable efficacy as first-line regimens in pts with LAPC and mPDAC, but larger matched cohorts are needed for validation. To this aim, a multicenter, observational, Italian study using target trial emulation (APOLLO) is currently ongoing. pts characteristics balanced after IPTW. Characteristic Overall N = 101 FOLFIRINOX N = 26 PAXG N = 75 p-value Adjusted standardized mean differences Age (median, IQR) 60 (55.7, 65.2) 61 (56.1, 66.5) 60 (53.1, 64.7) 0.200 -0.15 Stage 0.017 LAPC 22.0 (21.8) 10.0 (38.5) 12.0 (16.0) metastatic 79.0 (78.2) 16.0 (61.5) 63.0 (84.0) 0.09 BMI 0.040 normal 47.0 (46.5) 13.0 (50.0) 34.0 (45.3) -0.06 overweight 29.0 (28.7) 11.0 (42.3) 18.0 (24.0) -0.01 underweight 25.0 (24.8) 2.0 (7.7) 23.0 (30.7) 0.08 CA19-9 (kU/L) 11.0 (7.6, 13.4) 8.8 (5.9, 11.9) 11.5 (8.5, 13.7) 0.006 0.08 Missing 6 2 4 0.00 ECOG PS 0.600 0 63.0 (62.4) 15.0 (57.7) 48.0 (64.0) -0.04 ≥1 38.0 (37.6) 11.0 (42.3) 27.0 (36.0) Abbreviations: BMI: body mass index; ECOG PS: Eastern Cooperative Oncology Group Performance Status; LAPC locally advanced pancreatic disease;