Phase I/II study of vemurafenib in patients with unresectable or recurrent melanoma with BRAF(V) (600) mutations.

We investigated the efficacy and safety of vemurafenib in Japanese patients with unresectable or recurrent melanoma with BRAF(V) (600) mutations. This was a two-step open-label multicenter phase I/II study. Step 1 evaluated the initial safety of vemurafenib 960 mg administrated p.o. twice daily in three patients. In step 2, eight patients received vemurafenib 960 mg administrated p.o. twice daily for 28-day treatment cycles; the primary outcome measure was response rate, as determined by independent review committee using Response Evaluation Criteria in Solid Tumors version 1.1. Adverse events (AE) experienced by five or more patients were arthralgia (n = 10), myalgia (n = 8), alopecia (n = 7), and rash, maculopapular rash and decreased appetite (n = 5 each). Three patients had grade 3 AE. One serious AE occurred in one patient (abnormal hepatic function). Six patients required dose reduction because of AE. One patient died within 28 days after the last dose, but death was caused by disease progression and not associated with the study drug. In the eight patients in step 2, overall response rate was 75.0%, none had a complete response and six had a partial response (75.0%). Median response duration was 240.0 days, disease control rate 87.5%, median progression-free survival 416.0 days and median overall survival 443.0 days. In conclusion, vemurafenib treatment resulted in an overall response rate of 75% in Japanese patients with metastatic melanoma with BRAF(V) (600) mutations. All toxicities were manageable.