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Published byBertha Bishop Modified over 8 years ago
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What are the main benefits of BRAF inhibitors in metastatic melanoma?
Should patients expect prolonged overall survival, prolonged progression-free survival, or simply palliation without chance of a cure?
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Vemurafenib in previously untreated Stage IV BRAFV600 mutant melanoma (BRIM3 trial): Overall survival Overall survival (%) Hazard ratio 0.70 (95% CI, 0.57–0.87) P<0.001 (post-hoc) at February 1, 2012 cutoff Censored at crossover 100 90 80 70 60 50 40 30 20 10 6 12 24 18 Vemurafenib (n = 337) Median f/u 12.5 months DTIC (n = 338) Median f/u 9.5 months 9.7 13.6 Months No. at risk Dacarbazine Vemurafenib 338 337 244 326 173 280 111 231 79 178 50 109 24 44 4 7 1 Chapman et al, ASCO 2012; #8502
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Sosman et al, N Engl J Med 2012; 366: 707–14
Vemurafenib in previously treated Stage IV BRAFV600 mutant melanoma (BRIM2 trial): Progression-free survival Progression-free Survival (%) 100 80 60 40 20 90 70 50 30 10 6.9 12 24 6 18 Months No. at risk 132 118 88 67 48 33 31 22 12 5 Treatment duration (weeks) Sosman et al, N Engl J Med 2012; 366: 707–14
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Sosman et al, N Engl J Med 2012; 366: 707–14
Vemurafenib in previously treated Stage IV BRAFV600 mutant melanoma (BRIM2 trial): Overall survival Overall Survival (%) 100 80 60 40 20 90 70 50 30 10 15.9 12 6 18 24 Months No. at risk 132 128 118 97 83 77 70 60 39 18 1 Treatment duration (weeks) Sosman et al, N Engl J Med 2012; 366: 707–14
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Dabrafenib in previously untreated Stage IV BRAFV600 mutant melanoma (BREAK3 trial): Progression-free survival (independent review) Proportion Alive Without Progression Hazard ratio (95% CI, 0.20–0.61) (Dec 19, 2011 cut-off) 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Dabrafenib DTIC 2.9 6.7 1 2 3 4 5 6 7 8 9 187 182 167 112 98 39 28 63 53 32 16 12 Months No. at risk Hauschild et al, ASCO 2012; LBA8500 Hauschild et al, Lancet 2012; 380: 358–65
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Flaherty et al, N Engl J Med 2012; 367: 1694–703
Open label study of combined BRAF/MEK inhibition in stage IV melanoma: Progression-free survival Estimated survival function Median (mos) HR (95% CI) P 12 mo. PFS (%) Mono D 5.8 9 D150/T1 9.2 0.56 (0.37, 0.87) 0.006 26 D150/T2 9.4 0.39 (0.25, 0.62) <0.0001 41 1.0 0.8 0.6 0.4 0.2 Median follow up time 14 mo 5.8 9.2 9.4 0.0 3 6 9 12 15 18 Patients at risk Months 54 46 25 13 2 47 33 26 11 1 52 36 29 15 Long et al, ESMO 2012; LBA27 Flaherty et al, N Engl J Med 2012; 367: 1694–703
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Benefits of BRAF inhibition
Front line BRAF inhibitors provide Significant PFS (5–7 months) Prolonged survival (13–18 months) There are few data on cures <10% of the BRIM2 patients are alive free of disease 3–5 years from treatment The drugs provide significant palliation, especially in patients with rapidly growing or symptomatic disease
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