We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Phase 1 study of the combination of vemurafenib, carboplatin, and paclitaxel in patients with BRAF-mutated melanoma and other advanced malignancies.
- Authors
Bhatty, Minny; Kato, Shumei; Piha‐Paul, Sarina A.; Naing, Aung; Subbiah, Vivek; Huang, Helen J.; Karp, Daniel D.; Tsimberidou, Apostolia M.; Zinner, Ralph G.; Hwu, Wen‐Jen; Javle, Milind; Patel, Sapna P.; Hu, Mimi I.; Varadhachary, Gauri R.; Conley, Anthony P.; Ramzanali, Nishma M.; Holley, Veronica R.; Kurzrock, Razelle; Meric‐Bernstam, Funda; Kwang Chae, Young
- Abstract
<bold>Background: </bold>BRAF inhibitors are effective against selected BRAFV600 -mutated tumors. Preclinical data suggest that BRAF inhibition in conjunction with chemotherapy has increased therapeutic activity.<bold>Methods: </bold>Patients with advanced cancers and BRAF mutations were enrolled into a dose-escalation study (3+3 design) to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs).<bold>Results: </bold>Nineteen patients with advanced cancers and BRAF mutations were enrolled and received vemurafenib (480-720 mg orally twice a day), carboplatin (area under the curve [AUC] 5-6 intravenously every 3 weeks), and paclitaxel (100-135 mg/m2 intravenously every 3 weeks). The MTD was not reached, and vemurafenib at 720 mg twice a day, carboplatin at AUC 5, and paclitaxel at 135 mg/m2 were the last safe dose levels. DLTs included a persistent grade 2 creatinine elevation (n = 1), grade 3 transaminitis (n = 1), and grade 4 thrombocytopenia (n = 1). Non-dose-limiting toxicities that were grade 3 or higher and occurred in more than 2 patients included grade 3/4 neutropenia (n = 5), grade 3/4 thrombocytopenia (n = 5), grade 3 fatigue (n = 4), and grade 3 anemia (n = 3). Of the 19 patients, 5 (26%; all with melanoma) had a partial response (PR; n = 4) or complete response (CR; n = 1); these responses were mostly durable and lasted 3.1 to 54.1 months. Of the 13 patients previously treated with BRAF and/or mitogen-activated protein kinase kinase (MEK) inhibitors, 4 (31%) had a CR (n = 1) or PR (n = 3). Patients not treated with prior platinum therapy had a higher response rate than those who did (45% vs 0%; P = .045).<bold>Conclusions: </bold>The combination of vemurafenib, carboplatin, and paclitaxel is well tolerated and demonstrates encouraging activity, predominantly in patients with advanced melanoma and BRAFV600 mutations, regardless of prior treatment with BRAF and/or MEK inhibitors.
- Subjects
MELANOMA treatment; CARBOPLATIN; PACLITAXEL; ANTINEOPLASTIC agents; SKIN cancer
- Publication
Cancer (0008543X), 2019, Vol 125, Issue 3, p463
- ISSN
0008-543X
- Publication type
journal article
- DOI
10.1002/cncr.31812