LBA62 - Preoperative modified FOLFIRINOX (mFOLFIRINOX) with or without chemoradiation (CRT) in borderline resectable pancreatic cancer (BRPC): Results from the randomized phase II trial PANDAS/PRODIGE 44

Background

The role and the safety of CRT following mFOLFIRINOX administration in BRPC is unknown.

Methods

Patients (pts) with ECOG PS 0/1 and BRPC defined according to centrally-reviewed radiographic NCCN criteria received neoadjuvant mFOLFIRINOX for 4 cycles. Those who had tumour controlled at restaging were randomized between two additional cycles of mFOLFIRINOX (arm A) alone or followed by a CRT (50.4 Gy in 28 fractions with capecitabine 825mg/m2 BID 5 days a week) prior to surgery. Patients without disease progression then underwent a pancreatectomy and adjuvant chemotherapy for 3 months (gemcitabine or 5-FU/folinic acid before 6/2008, mFOLFIRINOX thereafter). The primary endpoint was R0 resection (ITT analysis). Main secondary endpoints were overall survival (OS), locoregional relapse-free survival, metastasis-free survival and toxicity.

Results

Among the 248 patients who were assessed for eligibility, 139 patients had a BRPC according to external radiographic review. Hundred and thirty patients were enrolled and 110 patients were finally randomized (54 pts arm A; 56 pts arm B). Median age (A: 66y, B: 61y), median CA 19-9 level (A: 65 U/ml, B: 169 U/ml) and ECOG PS (A: 62% PS 0, B: 52% PS 0) of registered pts were similar between arms. Thirty pts did not have a pancreatic resection due to tumor progression (7 pts arm A; 13 pts arm B), unresectable disease (1 pt arm A), physician or pt decision (4 pts arm A, 1 pt arm B), adverse event (1 in each arm), COVID-19 infection (1 pt arm A), or death (1 pt arm B). Thirty-seven pts (69%) in arm A and 31 pts (55%) in arm B had tumor resection. R0 resection was achieved in 20/37 pts (54.1%) in arm A and 18/31 pts (58.1%) in arm B. ypCR was observed in 3 pts (8.1%) in arm A and 9 (29%) in arm B. The median OS was 32.8 months (95%CI: 22.7 – 55.4) in arm A and 30 months (95%CI: 16.5 – nr) in arm B. Among pts who underwent pancreatectomy, the median OS was 35.7 months (95%CI: 22.2 – 55.4) and 47.9 months (95%CI: 23.3 – nr) in arm A and B, respectively.

Conclusions

Neoadjuvant mFOLFIRINOX was associated with favorable OS but mFOLFIRINOX with conventional CRT did not improve R0 nor OS compared to mFOLFIRINOX without preoperative CRT in patients with BRPC.

Clinical trial identification

NCT02676349.

Editorial acknowledgement

Legal entity responsible for the study

T. Conroy.

Funding

PRODIGE (Partenariat de Recherche en Oncologie Digestive) 44 was supported by R&D Unicancer and a Clinical Research Hospital Program grant (PHRC) from the French Ministry of Health.

Disclosure

A. Lambert: Financial Interests, Personal, Advisory Board: Amgen, Servier, AstraZeneca, MSD, Merck, AAA, Deciphera. J. Bachet: Financial Interests, Personal, Other, consultancy: AbbVie; Financial Interests, Personal, Other, Consultancy: Acobiom; Financial Interests, Personal, Invited Speaker: Amgen, Leo Pharma, Viatris; Financial Interests, Personal, Advisory Board: Bayer, Biomunex, BMS, GSK, Merck Serono, MSD, Pierre Fabre, Servier, Takeda; Financial Interests, Institutional, Research Grant: Daichi, AstraZeneca, Roche. All other authors have declared no conflicts of interest.