Rechallenge strategies with anti-epidermal growth factor receptor (EGFR) drugs have been evaluated in patients (pts) with refractory RAS/BRAF wild type (WT) mCRC after response to anti-EGFR based 1st line therapy. Given the role of cetuximab in enhancing antibody-dependent cellular cytotoxicity (ADCC) and promoting expression of MHC class II molecules on dendritic cells, its association with anti-PD-L1 avelumab may be a relevant rechallenge strategy in RAS WT mCRC.
CAVE mCRC, a single arm multi-centre phase II study, aims to evaluate the efficacy of avelumab and cetuximab in RAS WT mCRC pts treated in first line with chemotherapy (CT) in combination with anti-EGFR drugs and who achieved a complete (CR) or partial response (PR). Primary endpoint is median overall survival (mOS), secondary endpoints are overall response rate (ORR) according to RECIST 1.1, progression free survival (PFS) and safety profile. This study seeks to demonstrate a mOS of 11 months (mo) for the experimental combination in comparison with historical mOS of 8.0 mo with standard third line treatments, which corresponds to an improvement in mOS of 37,5 %.
From August 10, 2018 to February 21, 2020, 77 pts have been enrolled and started treatment with avelumab 10 mg/kg q14 and cetuximab at 400 mg/m2 and subsequently 250 mg/m2 weekly until progression of disease (PD) or unacceptable toxicity. Kaplan-Meier curves estimated for the whole intention-to-treat (ITT) population (77 pts): mOS was 13.1 mo (95% Confidence Interval CI, 7.4-18.8 mo; 32 events); mPFS, 3.6 mo (95% CI, 3.3-3.9 mo; 62 events). Among 65 pts evaluable for response, 1 pt (1.5%) experienced CR, 3 pts (4.6%) PR, 32 pts stable disease (SD) (49.2%); 29 pts PD (44.6%). Pts with PFS≥ 6 mo were 12/65 (18.5%). Grade-3 adverse events were reported in 16/77 pts (22%), the most common being skin rash 10/77 (13%) and diarrhoea 3/77 (4%).
At this preliminary analysis, avelumab plus cetuximab as a rechallenge strategy is effective and well tolerated in chemorefractory RAS/BRAF WT mCRC pts. The final analysis for OS will be presented at the ESMO 2020 congress.
Clinical trial identification
Legal entity responsible for the study
Department of Precision Medicine, Università degli Studi della Campania \"L. Vanvitelli\".
E. Martinelli: Advisory/Consultancy: Amgen, Bayer, Merck-Serono, Roche, Sanofi, Servier, Pierre Fabre. T. Troiani: Advisory/Consultancy: Roche, Merck, Sanofi, Servier, Novartis, Bayer. F. Pietrantonio: Advisory/Consultancy: Amgen, Roche, Lilly, Sanofi, Merck-Serono, Bayer, Servier; Research grant/Funding (self): BMS. A. Avallone: Advisory/Consultancy: Amgen ; Speaker Bureau/Expert testimony: Servier . N. Normanno: Advisory/Consultancy: MSD, Qiagen, Biocartis, Incyte, Roche, BMS, MERCK, Thermofisher,Boehringer Ingelheim, Astrazeneca, Sanofi, Eli Lilly, Bayer. E. Maiello: Advisory/Consultancy: Astra Zeneca, Eli Lilly, Servier, Sanofi Genzyme, Roche, Merck, Eisai, Pfizer. A. Falcone: Advisory/Consultancy: Bayer, Bristol, Eli Lilly, Merck, Pierre-Fabre, Roche, Servier, and institutional support for clinical trials from Astra-Zeneca, Bayer, Bristol, Eli Lilly, Merck, MSD, Novartis, Roche, Sanofi, and Servier. C. Pinto: Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS, MSD, Bayer, Astra-Zeneca, Roche, Merck, Lilly, Servier, Sanofi, Astellas. F. Ciardiello: Advisory/Consultancy: Roche, Amgen, Merck, Pfizer, Sanofi, Bayer, Servier, BMS, Cellgene, Lilly; Research grant/Funding (self): Bayer, Roche, Merck, Amgen, AstraZeneca, Takeda. All other authors have declared no conflicts of interest.