Abstract 416P
Background
Panitumumab (P) plus FOLFOX is standard treatment for first-line RAS WT mCRC patients (pts). The value of P rechallenge is currently unknown, although pts with RAS mutation in liquid biopsy (LB) do not benefit from this strategy (Cremolini, JAMA Oncol 2019). We assessed P administration beyond progression to first-line P-FOLFOX in pts with mCRC and no RAS mutations detected in LB.
Methods
In this multicenter, phase II randomized trial, pts were assigned in a 3:2 ratio to second-line FOLFIRI with P (6 mg/kg) (Arm A) or without P (Arm B)). Stratification was done by primary sidedness (right vs left) and time from the last dose of P (≤ 3 months vs >3 months). LB biopsies for ctDNA analysis were collected at study entry and at disease progression with Idyilla technology. Primary endpoint was 6-month progression-free survival (PFS), analyzed by intention to treat. Two stage Simon design was planned: in the first stage, a minimum of 5 of 15 pts without progression at 6 months in arm A was required for a total of 85 pts after the second stage (51 in arm A and 34 in arm B).
Results
Between Feb 14, 2019, and Nov 10, 2020, 49 pts were screened (16 excluded due RAS mutations in LB and 2 other reasons) and 31 included (18 pts were assigned to arm A and 13 pts to arm B). Median follow up was 9.5 months (IQR 6.0, 13.0) in arm A and 7.0 months (IQR 5.0, 9.0) in arm B. Serious adverse events were more frequent in arm A (44% vs 23%). RR was 33% (95% CI 13, 59) vs 7.7% (95% CI 0.2, 36) in arms A and B. Median PFS was 11.0 months (95% CI 4.0-14.0) for arm A and 4.0 months (95% CI 2.0-8.0) for arm B (hazard ratio (HR) 0.5843, 95% CI 0.256-1.334; log-rank test p=0.1837). 6-month PFS was 66.7% (95% CI 40.9-86.6) vs 38.46% (95% CI 13.8-68.4); p= 0.09. RAS or BRAF mutations in LB biopsies were found in 4 (36%) and 2 (22%) pts in arms A and B at disease progression. The study was prematurely closed due to inadequate recruitment.
Conclusions
Second-line FOLFIRI + P beyond progression to FOLFOX + P deserves further investigation in RAS wild-type mCRC pts selected by LB.
Clinical trial identification
EudraCT 2017-004519-38.
Editorial acknowledgement
Study conducted with the assistance of PIVOTAL SLU Abstract writen by Jose M Vieitez.
Legal entity responsible for the study
Grupo Español Multidisciplinar en Cáncer Digestivo (GEMCAD).
Funding
Amgen.
Disclosure
J. Aparicio: Financial Interests, Personal, Advisory Board: Amgen; Merck; Sanofi; Servier; Bayer; Pierre Fabre. A.C. Virgili Manrique: Financial Interests, Personal, Invited Speaker: Amgen; Sanofi; Servier; Merck; Roche; Financial Interests, Personal, Advisory Board: Roche; Amgen; Financial Interests, Personal, Other: Amgen; Sanofi; MSD; Servier. J. Capdevila: Financial Interests, Personal, Speaker’s Bureau: Amgen; Bayer; AAA; AstraZeneca; Eisai; Exelixis; Ipsen; ITM; Hudchinson Pharma; Lilly; Merck; Novartis; Pfizer; Sanofi; Financial Interests, Personal, Advisory Board: Amgen; Bayer; AAA; AstraZeneca; Eisai; Exelixis; Ipsen; ITM; Hudchinson Pharma; Lilly; Merck; Novartis; Pfizer; Sanofi; Financial Interests, Personal, Invited Speaker: Amgen; Bayer; AAA; AstraZeneca; Eisai; Exelixis; Ipsen; ITM; Hudchinson Pharma; Lilly; Merck; Novartis; Pfizer; Sanofi. D. Paez: Financial Interests, Personal, Speaker’s Bureau: Amgen; Hoffman-la Roche; Advanced Accelerator Applications; Financial Interests, Personal, Advisory Board: Sanofi; Ipsen; Amgen. J. Hernando: Financial Interests, Personal, Speaker’s Bureau: Adacap; Novartis; Roche; Ipsen; Eisai; Angelini; Pfizer. R. Vera: Financial Interests, Personal, Advisory Board: Roche; Amgen; Sanofi; Merk; Bristol-Myers; MSD; Servier; Bayer; AstraZeneca; Lilly; Financial Interests, Personal, Speaker’s Bureau: Roche; Amgen; Sanofi; Merk; Bristol-Myers; MSD; Servier; Bayer; AstraZeneca; Lilly; X. Hernandez: Financial Interests, Personal, Advisory Board: Sanofy-Aventis; Amgen. M.C. Riesco-Martinez: Financial Interests, Personal, Invited Speaker: Servier; Merk; Financial Interests, Personal, Advisory Board: AAA. J. Maurel: Financial Interests, Personal and Institutional, Research Grant: Merck; Biocartis; Incyte; NanoString; Amgen; Roche; Financial Interests, Personal, Other: Roche; Sanofi; Servier; Bayer; Astra-Zeneca; Shire; Pierre-Fabre; Sirtex; Fundación Clínica Universitaria; Cancer Expert Now; Advance Medical; Financial Interests, Personal and Institutional, Research Grant: Fundacion Olga Torres; Instituto de Salud Carlos III; Fundació la Marató de TV3; Catalan Agency for Management of University and Research. All other authors have declared no conflicts of interest.