Emerging treatment options for BRAF-mutant colorectal cancer

Figures & data

Table 1 Completed trials of targeted therapies in metastatic CRC with a BRAF^V600E mutation

Trial	Reference	Trial design	Intervention arm	Control arm	Summary of results
NCT00405587	Kopetz et al^Citation8	Open label, Phase II, single arm	Vemurafenib 960 mg BID (N=21)	NA	One partial response (5%); seven patients with stable disease. Median PFS of 2.1 months
NCT01072175	Corcoran et al^Citation44	Open label, Phase I/II single arm	Dabrafenib (150 mg BID) plus trametinib (2 mg daily) (N=43)	NA	Five patients (12%) sustained a partial response or better; 24 patients (56%) with stable disease
NCT01750918	Corcoran et al^Citation46	Open label, Phase I/II	Dabrafenib 150 mg BID, trametinib 2 mg daily, and panitumumab 6 mg/kg every 14 days (N=35)	Dabrafenib 50 mg BID and panitumumab 6 mg/kg every 14 days (N=20)	Response rate in three-drug combination was 26%, with an additional 57% of patients achieving stable disease
NCT01719380	van Geel et al^Citation50	Phase Ib dose escalation	Encorafenib + cetuximab + alpelisib, with escalating doses (N=28)	Encorafenib + cetuximab (N=26)	Overall response rates of 19% and 18% were confirmed in two-drug and three-drug combinations, respectively. Median PFS was 3.7 and 4.2 months for two-drug and three-drug combinations, respectively
NCT02164916	Kopetz et al^Citation52	Randomized Phase II	Irinotecan (180 mg/m^Citation2) and cetuximab (500 mg/m^Citation2) every 14 days, plus vemurafenib (960 mg PO BID) (N=54)	Irinotecan (180 mg/m^Citation2) and cetuximab (500 mg/m^Citation2) every 14 days (N=52)	Median PFS 4.4 vs 2.0 months (HR 0.42; 95% CI 0.26–0.66; P<0.001). ORR 16 vs 4% (P=0.09). Disease control rate of 67 vs 22% (P<0.001)

Abbreviations: BID, twice a day; CRC, colorectal cancer; HR, hazard ratio; NA, not applicable; ORR, overall response rate; PFS, progression-free survival; PO, by mouth.

Figure 1 Targeted therapy approaches in clinical trials for BRAF^V600E mutant CRC.

Abbreviation: CRC, colorectal cancer.

Figure 2 Schematic representation of the Phase III study of encorafenib + cetuximab plus or minus binimetinib vs irinotecan/cetuximab or infusional 5-FU/FA/irinotecan (FOLFIRI)/cetuximab with a safety lead-in of encorafenib + binimetinib + cetuximab in patients with BRAF^V600E-mutant metastatic CRC (BEACON CRC).

Abbreviations: CRC, colorectal cancer; FA, folinic acid; 5-FU, 5-fluorouracil; FOLFIRI, 5-fluorouracil, leucovorin and irinotecan.

Kopetz S, Desai J, Chan E, et al. Phase II pilot study of vemurafenib in patients with metastatic BRAF-mutated colorectal cancer. J Clin Oncol. 2015;33(34):4032–4038.

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Corcoran RB, Atreya CE, Falchook GS, et al. Combined BRAF and MEK inhibition with dabrafenib and trametinib in BRAF V600-mutant colorectal cancer. J Clin Oncol. 2015;33(34):4023–4031.

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Corcoran RB, Andre T, Atreya CE, et al. Combined BRAF, EGFR, and MEK inhibition in patients with BRAFV600E-mutant colorectal cancer. Cancer Discov. Epub 2018 Feb 05.

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van Geel RMJM, Tabernero J, Elez E, et al. A phase Ib dose-escalation study of encorafenib and cetuximab with or without alpelisib in metastatic BRAF-mutant colorectal cancer. Cancer Discov. 2017;7(6):610–619.

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Kopetz S, McDonough SL, Morris VK, et al. Randomized trial of irinotecan and cetuximab with or without vemurafenib in BRAF-mutant metastatic colorectal cancer (SWOG 1406). J Clin Oncol. 2017;35(4_suppl):520.

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