LBA30 - Panitumumab (P) + FOLFIRINOX or mFOLFOX6 in unresectable metastatic colorectal cancer (mCRC) patients (pts) with RAS/BRAF wild-type (WT) tumor status from circulating DNA (cirDNA): First results of the randomised phase II PANIRINOX-UCGI28 study

Background

For shrinkage of RAS/BRAF WT tumors, anti-EGFR antibodies combinated with triplet chemotherapy (CT) regimen have shown promising results in phase I-II trials. Ultrasensitive cirDNA analysis as those with IntPlex® technology might result in better selection of super-responders to anti-EGFR-based therapies. Thus, the aim of PANIRINOX was studying the complete response (CR) rate obtained with P plus a tri-CT regimen (FOLFIRINOX = Arm A) or a standard bi-CT (mFOLFOX6 = Arm B) in pts with cirDNA-based RAS/BRAF V600E WT unresectable mCRC tumors.

Methods

In this randomised non-comparative multicentric phase II trial, pts were assigned in a 2:1 ratio in arm A/B (12 cycles max) in 2 different strata (str) according to disease extent (str 1: liver limited /str2: non-liver-limited). Primary endpoint was the CR rate according to RECIST 1.1 (central review) and CEA normalization (Fleming’s one-step design, one-sided a=5%, b=10%, H0: 3%; H1: 12%; 60 pts in Arm A needed with at least 4 successes; Arm B as internal control). Secondary endpoints included progression-free and overall survival (PFS and OS).

Results

From 10/2017 to 07/2022, 78/33 pts were assigned in arm A/B in str2. Main characteristics were (arm A/B): median age 64/62 yo; males 67/45%; PS0 63/42%; left-sided 81/79%; synchronous metastases 85/87%; >1 metastatic site 82/72%. The table lists CR, PFS and OS in evaluable pts. Main grade≥3 treatment-related adverse events were (arm A/B): diarrhea 39/9%, peripheral neuropathy 22/24%, skin 18/24%. Table: LBA30

Conclusions

With 5 pts achieving CR in arm A and 95%CI including predetermined hypothesis in arm B, the study met its primary objective in str2. We confirm that genotyping tumors from cirDNA analysis is a relevant alternative to tissue before administrating anti-EGFR-based therapies in first line.

Clinical trial identification

EudraCT 2016-001490-33, NCT02980510.

Editorial acknowledgement

Legal entity responsible for the study

UNICANCER.

Funding

Amgen.

Disclosure

T. Mazard: Financial Interests, Personal, Advisory Board: Pierre Fabre, Pierre Fabre, Serivier, AAA; Financial Interests, Personal, Invited Speaker: Servier, Sanofi; Financial Interests, Personal, Other, Development of clinical cases for regional meetings: Merck Serono; Financial Interests, Institutional, Coordinating PI: Amgen; Non-Financial Interests, Other, development of guidelines about molecular testing in colorectal cancers: INCA; Other, travel grant: Pierre Fabre, Merck Serono, Sanofi. D. Botsen: Non-Financial Interests, Institutional, Training: Amgen, Sanofi, MSD, Merck Sarono, Pierre Fabre; Non-Financial Interests, Institutional, Coordinating PI: Servier. All other authors have declared no conflicts of interest.