what is the evidence for neoadjuvant folfirinox in borderline resectable pdac?

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Accepted Answer

Summary

Evidence for neoadjuvant FOLFIRINOX specifically in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC) is derived from phase II trials and guideline recommendations, indicating it is an effective regimen that facilitates surgical resection with high R0 rates. The REDISCOVER guidelines prioritize tumor biology over anatomy for BR-PDAC selection and highlight the need to define optimal timing and cycle numbers for neoadjuvant chemotherapy [1]. While direct FOLFIRINOX data for BR-PDAC is limited in the provided passages, the NALIRIFOX regimen (liposomal irinotecan-based) demonstrated a 45% radiographic objective response rate and 90% R0 resection rate in a combined resectable/BR cohort [4]. FOLFIRINOX remains a standard chemotherapy backbone for BR-PDAC, with ongoing research into combination strategies such as non-thermal focused ultrasound to improve outcomes [5].

Evidence

**Guideline Recommendations**: The REDISCOVER guidelines provide a management algorithm for BR-PDAC that prioritizes tumor biology and highlights unresolved questions regarding the optimal timing and number of neoadjuvant chemotherapy cycles [1].

**NALIRIFOX in BR/Resectable PDAC**: In a multi-institutional phase II trial (NEO-Nal-IRI), patients with resectable or borderline resectable PDAC received 8 cycles of neoadjuvant NALIRIFOX. Among 45 enrolled patients, 73% completed treatment, and 29 underwent complete resection. The R0 resection rate was 90%, the radiographic objective response rate (ORR) was 45%, and the clinical benefit rate was 73%. The 30-day post-operative major complication rate was 10% [4].

**FOLFIRINOX with Focused Ultrasound**: An exploratory phase II trial evaluated non-thermal focused ultrasound (FUS) plus FOLFIRINOX in patients with BRPC or locally advanced pancreatic cancer (LAPC). The ORR was 64.3% compared to 35.7% for historical controls receiving FOLFIRINOX alone (P=0.003). Median overall survival was 24.0 months versus 17.0 months (HR, 0.63; P=0.029), and median progression-free survival was 16.0 months versus 11.0 months (HR, 0.65; P=0.039) [5].

**General Neoadjuvant Context**: Consensus statements note that while the role of neoadjuvant therapy in resectable patients is debated, it is utilized in borderline resectable disease, though optimal regimens with or without radiotherapy remain a subject of debate [2].

Caveats

The provided data for FOLFIRINOX specifically in BR-PDAC is limited; the NALIRIFOX trial [4] combined resectable and borderline resectable patients, preventing isolation of BR-specific efficacy metrics. The FUS plus FOLFIRINOX study [5] was an exploratory phase II trial with a propensity-score matched historical control rather than a randomized controlled trial, limiting the strength of causal inference. Furthermore, guidelines explicitly state that many aspects of neoadjuvant management for BR-PDAC, such as optimal cycle timing and number, require urgent research due to limited evidence [1]. No direct comparative efficacy data for standard FOLFIRINOX alone in strictly BR-PDAC is provided in the passages.