Abstract 429P
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 with controlled disease after FOLFIRI + cetuximab (8 cycles) were randomized (1:1) 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 count. 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) after initiation of maintenance therapy. A total of 134 randomized and evaluable patients (67 per arm) were required (Fleming’s one-step design, one-sided α=5%, β=20%, H0: 40%; H1: 55%). Among secondary endpoints, overall response rate (ORR) and progression-free survival (PFS) from randomization are available. RAS and BRAF status were centrally validated by NGS using the AmpliSeq™ Colon and Lung Panel v2.
Results
214 patients were included according to RAS status locally assessed in each center, and 139 randomized (67 arm A/72 arm B). Baseline characteristics were: median age, 64/68 years; ECOG PS 0, 55%/49%; single metastatic site, 58%/47%; right-sided primary, 24%/18%. The median follow-up was 29.6 months. Table: 429P
Results according to RAS and BRAF status
| Included | Randomized | |||||
| Arm A - cetuximab | Arm B - Observation | |||||
| All n=214 | BRAFV600E+RASwt n=184 (86%) | All n=67 | BRAFV600E+RASwt n=60 (90%) | All n=72 | BRAFV600E+RASwt n=66 (92%) | |
| ORR (%) before randomization | 55 | 58 | 75 | 78 | 69 | 68 |
| 6-month PFR (%) after randomization [95% CI] | - | - | 39 [27; 52] | 42 [29; 55] | 7 [2; 16] | 8 [3; 17] |
| Median PFS (months) after randomization [95% CI] | - | - | 5.3 [3.7; 7.4] | 5.7 [3.7; 7.7] | 2.0 [1.8; 2.4] | 2.0 [1.8; 2.7] |
Conclusions
Although the cetuximab maintenance arm did not meet the primary objective, a clinically meaningful difference in PFS in favor of cetuximab maintenance was found in RAS/BRAF wt mCRC patients.
Clinical trial identification
NCT02404935.
Editorial acknowledgement
Legal entity responsible for the study
UNICANCER.
Funding
Merck Serono S.A.S.
Disclosure
V. Boige: Financial Interests, Personal and Institutional, Other, consulting, training, clinical research, travel, accomodations, expenses: Merck; Financial Interests, Personal, Other, consulting: Eisai; Ipsen; BMS; Financial Interests, Personal, Other, consulting, training, clinical research, travel, accomodations, expenses: Bayer; Roche; Sanofi Genzyme; Financial Interests, Personal, Other, training, clinical research, travel, accomodations, expenses: Amgen; Financial Interests, Personal, Training: MSD; Novartis; Financial Interests, Personal, Other, consulting: Daiichi Sankyo; Prestizia. E. Francois: Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Roche; Financial Interests, Personal, Other, honoraria, travel, accomodations, expenses: Servier; MSD; Novartis; Amgen. M. Ben Abdelghani: Financial Interests, Personal, Other, consulting, travel, accomodations, expenses, expert testimony: Sanofi; Servier; Bayer; Ipsen; Amgen. Financial Interests, Personal, Other, travel, accomodations, expenses, expert testimony: Roche. J.M. Phelip: Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses, research funding: Merck; Roche; Bayer; Sanofi; Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Amgen; Servier; Msd; Pierre Fabre. V. Hautefeuille: Financial Interests, Personal, Invited Speaker: Novartis; Merck; Amgen; Financial Interests, Personal, Advisory Board: Ipsen; Sanofi Aventis; AAA. C. de la Fouchardiere: Financial Interests, Personal, Other, consulting, travel, accomodations, expenses: Servier; Eisai; Roche; Financial Interests, Personal, Other, consulting: Bayer; Lilly; Pierre Fabre; MSD; Financial Interests, Personal, Other, travel, accomodations, expenses: Amgen; BMS. H. Blons: Financial Interests, Personal, Training: AstraZeneca; BMS; MSD. O. Bouche: Financial Interests, Personal, Other, honoraria as a speaker and/or in an advisory role: Merck KgaA; Bayer; AstraZeneca; Grunenthal; MSD; Amgen; Servier; Pierre Fabre; Roche; Genentech. All other authors have declared no conflicts of interest.