PracticeUpdate: Haematology & Oncology

SKIN 30

Vemurafenib inmetastatic melanoma patients with brainmetastases Annals of Oncology Take-home message

1 by an independent review committee (IRC) was 18% (2 CRs, 14 PRs). Extracranial BORR by IRC was 33% in cohort 1 and 23% in cohort 2. Median PFS (brain only, investigator-assessed) was 3.7 months (range 0.03–33.4; IQR 1.9–5.6) in cohort 1 and 4.0 months (range 0.3–27.4; IQR 2.2–7.4) in cohort 2. Median OS was 8.9 months (range 0.6–34.5; IQR 4.9–17.0) in cohort 1 and 9.6 months (range 0.7–34.3; IQR 4.5–18.4) in cohort 2. Adverse events (AEs) were similar in type, grade and frequency to other studies of single- agent vemurafenib. Grade 3/4 AEs occurred in 59 (66%) patients in cohort 1 and 36 (64%) in cohort 2. Overall, 84% of patients died during the study (86% in cohort 1 and 80% in cohort 2), mainly due to disease progression. CONCLUSIONS The study demonstrates clinically meaningful response rates of melanoma BM to vemurafenib that was well tolerated and without significant CNS toxicity. Vemurafenib in metastatic melanoma patients with brain metastases: an open-label, single- arm, phase 2, multicentre study. Ann Oncol 2016 Dec 19;[EPub Ahead of Print], GA McArthur, M Maio, A Arance, et al.

• This phase II study assessed the performance of vemurafenib in patients with and without prior treatment for BRAF(V600)-mutated melanoma brain metastases (BM). The best intracranial overall response rate in patients with previously untreated BM was 18%. Extracranial best overall response rate was 33% among those with previously untreated BM and 23% among those with previously treated BM. • The results showed that melanoma BM responded in a clinically meaningful way to vemurafenib. This agent can be administered without causing significant CNS toxicity. Abstract

endpoint was best overall response rate (BORR) in the brain in cohort 1 that was evaluated using modified RECIST 1.1 criteria using lesions ≥0.5cm to assess response. RESULTS 146 patients were treated (cohort 1 n=90; cohort 2 n=56), 62% of whomwere male. Median (range) time since diagnosis of BM: 1.0 (0-9) month in cohort 1 and 4.2 (1–68) months in cohort 2. Median duration of treatment was 4.1 months (range 0.3-34.5) in cohort 1 and 4.1 months (range 0.2-27.6) in cohort 2. Intracranial BORR in cohort

BACKGROUND Vemurafenib has shown activity in patients with BRAF(V600) mutated melanoma with brain metastases (BM). This phase 2 study evaluated vemurafenib in patients with/without prior treatment for BM. METHODS Patients with BRAF(V600) mutated melanoma with BM were enrolled into cohort 1 (previously untreated BM) and cohort 2 (previously treated BM) and received vemurafenib (960 mg BID) until disease progression (PD) or intolerance. Primary

Discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma

British Journal of Cancer Take-home message

Abstract BACKGROUND A phase II randomised discontin- uation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. METHODS Patients received cabozantinib 100mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation pro- gression-free survival (PFS). RESULTS Seventy-seven patients were enrolled (62% cutaneous, 30% uveal, and 8%mucosal). At week 12, the ORR was 5%; 39% of patients had SD. During the lead-in phase, reduction in target lesions from baseline was seen in 55% of eval- uable patients overall and in 59% of evaluable patients with uveal melanoma. Median PFS after randomisation was 4.1 months with cabozantinib and 2.8 months with placebo (hazard ratio of 0.59; P=0.284). Median PFS from study day 1 was 3.8 months, 6-month PFS was 33%, and median overall survival was 9.4 months. The most com- mon grade 3/4 adverse events were fatigue

(14%), hypertension (10%), and abdominal pain (8%). One treatment-related death was reported from peritonitis due to diverticular perforation. CONCLUSIONS Cabozantinib has clinical activity in patients with metastatic melanoma, including uveal melanoma. Further clinical investigation is warranted. Phase II randomised discontinuation trial of the MET/VEGF receptor inhibitor cabozantinib in metastatic melanoma. Br J Cancer 2017 Jan 19;[EPub Ahead of Print], A Daud, HM Kluger, R Kurzrock, et al.

• This was a phase II discontinuation trial conducted to assess the effect of cabozantinib, a TKI inhibitor, in a cohort of patients with metastatic melanoma. Cabozantinib 100 mg daily was given to the 77 participants during a 12-week lead-in, after which those with stable disease (39%) were randomised to either cabozantinib or placebo. The objective response rate at week 12 was 5%. Progression-free survival did not differ significantly between groups post randomization (4.1 months with cabozantinib and 2.8 months with placebo; HR, 0.59; P = 0.284). • Cabozantinib has clinical activity in patients with metastatic melanoma, meriting further clinical investigation.

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PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY