Vemurafenib improved survival in BRAF mutation–positive metastatic melanoma

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

[email protected]

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

[email protected]

Vemurafenib had a significant survival benefit compared with dacarbazine in adults with treatment-naive, BRAF^V600E and BRAF^V600K mutation–positive metastatic melanoma, investigators reported in the March issue of Lancet Oncology.

In the phase III trial, 675 patients with BRAF^V600 mutations were randomized to receive BRAF inhibitor vemurafenib (960 mg orally b.i.d.) or dacarbazine (1,000 mg/m² IV every 3 weeks). The median overall survival was 13.6 months among 337 patients randomized to receive vemurafenib, compared with 9.7 months for the 338 patients randomized to receive dacarbazine (hazard ratio, 0.70; 95% confidence interval, 0.57-0.87, P = .0008), reported Dr. Grant McArthur of Peter MacCallum Cancer Centre, East Melbourne, Australia, and his associates.

Researchers followed vemurafenib and dacarbazine patients for a median of 12.5 and 9.5 months, respectively. One-quarter of dacarbazine patients later crossed over to vemurafenib (Lancet Oncol. 2014;15:323-32).

Median progression-free survival times also favored vemurafenib (6.9 months vs. 1.6 months for dacarbazine; HR for vemurafenib, 0.38; 95% CI, 0.32-0.46, P less than .0001). Among those patients available for follow-up at 18 months, after crossover had occurred, the difference in overall survival was insignificant (39% for vemurafenib vs. 34% for dacarbazine), the investigators reported.

Although BRAF^V600E is the most common mutation in patients with metastatic melanoma, a substantial proportion of patients carry the BRAF^V600K mutation (8.6% in the current study), and data suggest that these patients might be at increased risk for brain and lung metastases and might have a shorter time from diagnosis to metastasis and death than patients with a BRAFV^V600E mutation, the investigators said.

Benefit from vemurafenib was found for both types of BRAF mutations. For the 598 patients with BRAF^V600E disease (91%), the median overall survival in the vemurafenib group was 13.3 months compared with 10.0 months in the dacarbazine group (HR, 0.75; 95% CI, 0.60-0.93, P = .0085). For the 57 patients with BRAF^V600K disease (9%), the median overall survival in the vemurafenib group was 14.5 months (95% CI, 11.2 to not estimable) compared with 7.6 months in the dacarbazine group (HR, 0.43; 95% CI, 0.21-0.90, P = .024), the investigators reported.

Grade 3-4 events included cutaneous squamous cell carcinoma (19%), keratoacanthomas (10%), rash (9%), and abnormal liver function tests (11%) in the vemurafenib group, and neutropenia (9%) in the dacarbazine group. Eight patients (2%) in the vemurafenib group developed new primary melanomas. The death rate due to adverse events was 2% in each group.

F Hoffman/La Roche/Genentech funded the trial. Dr. McArthur reported providing uncompensated services to Roche/Genentech. Sixteen of his associates reported receiving support from or serving as consultants or advisers to Roche, Roche/Genentech, or Genentech. Three other associates are employees of Roche/Genentech, Roche Molecular Systems, or F Hoffman/La Roche.

[email protected]