Title |
Phase II study of vemurafenib followed by ipilimumab in patients with previously untreated BRAF-mutated metastatic melanoma
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Published in |
Journal for Immunotherapy of Cancer, August 2016
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DOI | 10.1186/s40425-016-0148-7 |
Pubmed ID | |
Authors |
Asim Amin, David H. Lawson, April K.S. Salama, Henry B. Koon, Troy Guthrie, Sajeve S. Thomas, Steven J. O’Day, Montaser F. Shaheen, Bin Zhang, Stephen Francis, F. Stephen Hodi |
Abstract |
Ipilimumab (IPI), an anti-CTLA-4 antibody, and vemurafenib (VEM), a BRAF inhibitor, have distinct mechanisms of action and shared toxicities (e.g., skin, gastrointestinal [GI] and hepatobiliary disorders) that may preclude concomitant administration. Concurrent administration of IPI and VEM previously showed significant dose-limiting hepatotoxicity in advanced melanoma. This single-arm, open-label, phase II study evaluated a sequencing strategy with these two agents in previously untreated patients with BRAF-mutated advanced melanoma. This study was divided into two parts. During Part 1 (VEM1-IPI), patients received VEM 960 mg twice daily for 6 weeks followed by IPI 10 mg/kg every 3 weeks for 4 doses (induction), then every 12 weeks (maintenance) beginning at week 24 until disease progression or unacceptable toxicity. During Part 2 (VEM2), patients who progressed after IPI received VEM at their previously tolerated dose. The primary objective was to estimate the incidence of grade 3/4 drug-related skin adverse events (AEs) during VEM1-IPI. All patients who were initially treated with VEM (n = 46) received IPI induction therapy; 8 received IPI maintenance and 19 were treated during VEM2. During VEM1-IPI, the incidence of grade 3/4 drug-related AEs associated with the skin, GI tract, and hepatobiliary system was 32.6 %, 21.7 %, and 4.3 %, respectively. There were no drug-related deaths. At a median follow-up of 15.3 months, median overall survival was 18.5 months. Median progression-free survival was 4.5 months. VEM (960 mg twice daily for 6 weeks) followed by IPI 10 mg/kg has a manageable safety profile. The benefits/risks of BRAF inhibitors followed by immunotherapy should be evaluated further in light of continuing developments in treatment options for metastatic melanoma. ClinicalTrials.gov identifier: NCT01673854 (CA184-240) Registered 24 August 2012. |
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Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
Unknown | 55 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 14 | 25% |
Student > Bachelor | 8 | 14% |
Student > Ph. D. Student | 7 | 13% |
Other | 6 | 11% |
Student > Master | 6 | 11% |
Other | 6 | 11% |
Unknown | 9 | 16% |
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Agricultural and Biological Sciences | 7 | 13% |
Biochemistry, Genetics and Molecular Biology | 5 | 9% |
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Chemistry | 2 | 4% |
Other | 5 | 9% |
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