First-line treatment efficacy of anti-EGFR versus anti-VEGF antibodies in BRAF-mutated metastatic colorectal cancer according to primary tumor sidedness: A pooled analysis of seven clinical trials performed in the first-line treatment of mCRC (German AIO Study Group).

[BACKGROUND] Both BRAF-mutation and right-sided primary tumor location (PTL), have been associated with poor prognosis in metastatic colorectal cancer (mCRC). The present pooled analysis of individual patient data evaluates the efficacy of first-line chemotherapy combined with anti-EGFR- or anti-VEGF-directed therapy in BRAF-mut mCRC together with PTL.

[METHODS] We conducted a pooled analysis of seven first-line AIO-studies (FIRE-3, FIRE-4, FIRE-4.5, CIOX, XELAVIRI, PANAMA, VOLFI) including patients with BRAF-mut and RAS-wild-type mCRC.

[RESULTS] Among 209 evaluable patients, left-sided primary tumors (LSPT) were observed in 98 (46.9 %) compared to 111 (53.1 %) patients with right-sided primary tumors (RSPT). In the overall cohort, ORR was comparable (OR 0.85; 95 % CI 0.47-1.52), while median PFS was significantly shorter in patients receiving anti-EGFR-based therapy (HR 1.42; 95 % CI 1.05-1.91; P = 0.022), no major difference was observed with regard to OS (HR 0.96; 95 % CI 0.70-1.32; P = 0.80). Patients with LSPT showed comparable PFS (HR 0.98; 95 % CI 0.63-1.51), but a numerical OS benefit (HR 0.71; 95 % CI, 0.45-1.14) with anti-EGFR- compared to anti-VEGF-based therapy. This effect was observed independent of sex. In contrast, patients with RSPT showed both, inferior PFS (HR 2.09; 95 % CI 1.35-3.22; P < 0.001) and OS (HR 1.31; 95 % CI, 0.84-2.05). These effects were observed in male and female patients.

[CONCLUSIONS] The present analysis of BRAF-mut mCRC suggests a survival benefit from anti-EGFR- or anti-VEGF-directed antibodies in patients with LSPT. This effect was not observed in RSPT, where patients showed a clearly greater benefit from bevacizumab.