Abstract 387P
Background
Although anti-EGFR monoclonal antibodies are active as single-agent therapy in RAS wild-type (wt) metastatic colorectal cancer (mCRC), few studies are available on their role in maintenance therapy during chemotherapy (CT)-free intervals (CFI).
Methods
RAS wt unresectable mCRC patients (pts) with controlled disease after FOLFIRI + cetuximab (8 cycles) were randomized to receive maintenance with bi-weekly cetuximab alone (arm A) or observation (arm B) until disease progression (PD)/unacceptable toxicity/death. Randomization was stratified according to tumor response, center, baseline Köhne score, CEA and platelet. In case of tumor progression during the CFI, FOLFIRI + cetuximab was to be reintroduced for 8 cycles, followed by a new CFI. The primary objective of this multicenter non-comparative randomized phase II trial was the 6-month progression-free rate (PFR). A total of 134 randomized and evaluable pts (67 per arm) were required (Fleming’s one-step design, one-sided α=5%, β=20%, H0: 40%; H1: 55%). Secondary endpoints included overall survival (OS), time to treatment strategy failure (TTSF), and progression-free survival (PFS). RAS and BRAF status were centrally validated by NGS.
Results
214 pts were included according to RAS status locally assessed in each center, and 139 randomized (67 arm A/72 arm B). The median follow-up was 40 months. Overall, FOLFIRI + cetuximab could be reintroduced in 74% of pts, and ≥ 2 times in 21% of pts in arm A and 36% in arm B. In an exploratory multivariate analysis, the two significant prognostic factors for PFS were treatment arm and primary tumor site, and platelet count and primary tumor site for OS. Table: 387P
Results according to centralized RAS and BRAF status
| Randomized | ||||
| Arm ACetuximab | Arm BObservation | |||
| All n = 67 | BRAF V600E + RAS wt n = 60 (90%) | All n = 72 | BRAF V600E + RAS wt n = 66 (92%) | |
| 6-month PFR (%) [95% CI] from randomization | 39 [27; 52] | 42 [29; 55] | 6 [2; 14] | 6 [2; 15] |
| Median PFS (months) from randomization [95% CI] | 5.3 [3.7;7.4] | 5.7 [3.7; 7.7] | 2.0 [1.8;2.7] | 2.0 [1.8;2.8] |
| Median OS (months) from randomization [95% CI] | 24.8 [18.7;30.4] | 25.6 [19.4; 31.1] | 19.7 [13.3;24.4] | 19.7 [13.4;24.4] |
Conclusions
Although the cetuximab maintenance arm did not meet the primary objective, a clinically meaningful difference in PFS and OS in favor of cetuximab maintenance was found in pts with RAS/BRAF wt mCRC.
Clinical trial identification
NCT02404935 N° EudraCT: 2012-005139-99.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Merck Serono S.A.S.
Disclosure
V. Boige: Financial Interests, Personal and Institutional, Other, clinical research, consultant, training, congresses invitation: MERCK; Financial Interests, Personal, Other, consultant, training, congresses invitation: Sanofi Genzyme, Ipsen, Bayer, Roche; Financial Interests, Personal, Other, consultant: Eisai, Bms, Daiichi Sankyo Prestizia; Financial Interests, Personal, Other, training: Novartis; Financial Interests, Personal, Other, training, congresses invitation: MSD, Amgen. E. Francois: Financial Interests, Personal, Other, remunerated services and congress invitation: Pierre Fabre; Financial Interests, Personal, Other, remunerated services: Amgen, Viatris. H. Blons: Financial Interests, Personal, Training: AstraZeneca, BMS, MSD. M. Ben Abdelghani: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, BMS; Financial Interests, Personal, Other, congress invitation: Servier; Financial Interests, Personal, Principal Investigator: Bayer, Ipsen. J.M. Phelip: Financial Interests, Personal, Advisory Role: Merck, Amgen, Roche, Sanofi, Servier, Bayer, MSD, Pierre Fabre. V. Ly Lebrun: Financial Interests, Personal, Advisory Board: Ipsen. L. Mineur: Financial Interests, Institutional, Principal Investigator: Sanofi, Heliodx; Financial Interests, Personal, Invited Speaker: Amgen, Ipsen, Servier; Financial Interests, Personal, Other, invited speaker and congresses invitation: Merck; Financial Interests, Personal, Other, congresses invitation: Mundipharma. V. Hautefeuille: Financial Interests, Personal, Invited Speaker: Novartis, Merck, Amgen; Financial Interests, Personal, Advisory Board: AAA, Ipsen, Sanofi Aventis. C. de la Fouchardiere: Financial Interests, Personal, Advisory Board: Merck, Roche, Lilly, Bayer, Amgen, MSD, Servier, Pierre Fabre Oncologie, Bristol-Myers Squibb, Incyte, Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Ipsen, Eisai; Financial Interests, Institutional, Invited Speaker: Pierre Fabre Oncologie, Servier. O. Bouche: Financial Interests, Personal, Other, invited speaker and advisory role: Merck KGaA; Financial Interests, Personal, Invited Speaker, invited speaker and advisory role: Roche Genentech, Bayer, Astrazeneca, Grunenthal, MSD, Amgen, Servier, Pierre Fabre. All other authors have declared no conflicts of interest.