Abstract 440P
Background
Encorafenib and cetuximab is efficient in anti-EGFR-naïve patients (pts) with BRAF V600E mutated (BRAFm) metastatic colorectal cancer (mCRC) after failure of one or two prior lines of treatment (BEACON trial). However to date, the efficacy of BRAF inhibitors in combination with anti-EGFRs (B+E) in patients (pts) previously treated with an anti-EGFR agent has never been reported.
Methods
We collected retrospectively a series of pts with BRAFm mCRC treated with an anti-EGFR and anti-BRAF combination therapy after previous anti-EGFR treatment, in 11 French and Italian centers. PFS and OS were calculated since the start of the anti-BRAF therapies. Response and disease control rates (ORR, DCR) were also reported as treatment tolerability.
Results
A total of 19 BRAFm pts were enrolled (male: 8, median age: 61 [38-74], right-sided: 5, synchronous metastases: 10, >1 metastatic sites: 15, pMMR: 19). Prior to B+E treatment, 2/8/9 pts were treated with 1/2/>2 previous lines of therapy. 9 pts received previous panitumumab and 10 previous cetuximab. Immediate progression with previous anti-EGFR was reported for 6 pts. B+E treatment was encorafenib+cetuximab for 16 pts and dabrafenib+trametinib+panitumumab for 3 pts. Median B+E treatment duration was 4.7 months [1.8-10.1]. ORR (RECIST) was observed in 7 pts (37%), stable disease in 9 pts (47%) leading to a DCR of 84%. Median PFS was 4.6 months and median OS was 7.2 months. No difference was noted between pts previously treated with cetuximab or with panitumumab (DCR of 100% and 66%, p=0.09). Median PFS amongst pts with previous primary resistance to anti-EGFR agent was 5,4 months. Grade 3+ adverse events were experimented in 7 pts, but only 1 discontinued B+E due to drug-related AEs.
Conclusions
These results show, to our knowledge for the first time, the efficacy of the combination of anti-BRAF and anti-EGFRs in BRAFm mCRC pts previously treated with an anti-EGFR. The oncological outcomes observed here are very close to those reported in the BEACON pivotal trial. The use of an anti-BRAF and an anti-EGFR combination should not be ruled out in this population with limited therapeutic options and poor prognosis.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Julien Taieb.
Funding
Has not received any funding.
Disclosure
T. Lecomte: Financial Interests, Invited Speaker: AstraZeneca; Servier; Pierre Fabre; Financial Interests, Advisory Role: Ipsen; Amgen; Servier; Sanofi; Merck serono; Financial Interests, Principal Investigator: AstraZeneca; Ipsen; Astellas; Erythec pharma. M. Scartozzi: Financial Interests, Advisory Board: Amgen; BMS; Merck; MSD; Servier; Eisai; AstraZeneca; Financial Interests, Speaker’s Bureau: Merck; Servier; Eisai; Amgen. C. Gallois: Financial Interests, Invited Speaker: Servier; Financial Interests, Other: Amgen; Financial Interests, Invited Speaker: Sanofi. C. Cremolini: Financial Interests, Advisory Role: Roche; Merck; Servier; Bayer; Amgen; MSD; Financial Interests, Research Grant: Merck; Roche; Bayer; Servier. J. Taieb: Financial Interests, Advisory Board: Amgen; Celgene; Sirtex medical; Roche; Servier; Pierre Fabre; Lilly; Merck KgaA; MSD; Financial Interests, Invited Speaker, Hôpital Pompidou: Amgen; Financial Interests, Invited Speaker: Roche/ Genentech; Lilly; Servier; Pierre fabre; Merck; Sanofi; MSD. All other authors have declared no conflicts of interest.