Contemporary treatment approaches for metastatic colorectal cancer driven by BRAF V600 mutations

Table 1 Summary of selecting trials investigating the efficacy of targeted therapies in BRAF-mutant mutant metastatic colorectal cancer

Ref.	Design	Treatment arm(s)	Summary of results
Kopetz et al[30]	Phase 2	Vemurafenib (n = 21)	One (5%) patient had a partial response, 7 had stable disease. Median PFS was 2.1 mo
Yaeger et al[40]	Phase 2	Vemurafenib + Panitumumab (n = 15)	Two patients had partial responses; six achieved tumor shrinkage. Median PFS was 3.2 mo; median OS was 7.6 mo
Corcoran et al[44]	Phase 2	Dabrafenib + Trametinib (n = 43)	One patient had a complete response; five patients had a partial response, with an ORR of 12%; 56% of patients had stable disease
Corcoran et al[36]	Phase 1/2	Dabrafenib + Panitumumab (D + P) (n = 20) vs Dabrafenib + Trametinib + Panitumumab (D + T + P) (n=91) vs Trametinib + Panitumumab (T + P) (n = 31)	The ORR was 10%, 21%, and 0% for the D + P, D + T + P, and T + P, respectively. The median PFS was 3.5 mo in the D + P arm, 4.2 mo in the D + T + P arm, and 2.6 mo in the T + P arm
Kopetz et al[41], (SWOG 1406 trial)	Phase 2	Irinotecan + Cetuximab + Vemurafenib (n = 54) vs Irinotecan + Cetuximab (n = 52)	The median PFS 4.4 vs 2.0 mo (P < 0.001); the ORR 16% vs 4% (P = 0.09); disease control rate 67% vs 22% (P < 0.001)
van Geel et al[47]	Phase 2	Encorafenib + Cetuximab (n = 50) vs Encorafenib + Cetuximab + Alpelisib (n = 52)	The median PFS was 4.2 mo for encorafenib + cetuximab, and 5.4 mo for triplet therapy. The ORR rate was 22% and 27%, respectively
Kopetz et al[45], (BEACON CRC trial)	Phase 3	Encorafenib + Cetuximab + Binimetinib (Triplet arm) (n = 224) vs Encorafenib + Cetuximab (Doublet arm) (n = 220) vs Irinotecan/FOLFIRI + Cetuximab (Control arm) (n = 221)	The median OS was 9.0 mo in the triplet arm (HR for death vs control arm, 0.52; 95%CI: 0.39-0.70; P < 0.001), 8.4 mo in the doublet arm (HR for death vs control arm, 0.60; 95%CI: 0.45-0.79; P < 0.001), and 5.4 mo in the control arm. The ORR was 26%, 20%, and 2% for the triplet arm, the doublet arm, and the control arm, respectively

mCRC: Metastatic colorectal cancer; PFS: Progression-free survival; OS: Overall survival; ORR: Overall response rate; HR: Hazard ratio.