Efficacy of vemurafenib in patients with non–small-cell lung cancer with BRAF V600 mutation: An open-label, single-arm cohort of the histology-independent VE-Basket study Journal Article
| Authors: | Subbiah, V.; Gervais, R.; Riely, G.; Hollebecque, A.; Blay, J. Y.; Felip, E.; Schuler, M.; Gonçalves, A.; Italiano, A.; Keedy, V.; Chau, I.; Puzanov, I.; Raje, N. S.; Meric-Bernstam, F.; Makrutzki, M.; Riehl, T.; Pitcher, B.; Baselga, J.; Hyman, D. M. |
| Article Title: | Efficacy of vemurafenib in patients with non–small-cell lung cancer with BRAF V600 mutation: An open-label, single-arm cohort of the histology-independent VE-Basket study |
| Abstract: | PURPOSE To study whether BRAF V600 mutations in non–small-cell lung cancer (NSCLC) may indicate sensitivity to the BRAF inhibitor vemurafenib, we included a cohort of patients with NSCLC in the vemurafenib basket (VE-BASKET) study. On the basis of observed early clinical activity, we expanded the cohort of patients with NSCLC. We present results from this cohort. METHODS This open-label, histology-independent, phase II study included six prespecified cohorts, including patients with NSCLC, and a seventh all-comers cohort. Patients received vemurafenib (960 mg two times per day) until disease progression or unacceptable toxicity. The primary end point of the final analysis was objective response rate (Response Evaluation Criteria in Solid Tumors, version 1.1). Secondary end points included progression-free survival, overall survival, and safety. Because the prespecified clinical benefit endpoint was met in the initial NSCLC cohort, the cohort was expanded. RESULTS Sixty-two patients with BRAF V600–mutant NSCLC were enrolled and treated: 13% (n = 8) had received no prior systemic therapy, and 87% (n = 54) had received prior therapies. The objective response rate was 37.1% (95% CI, 25.2% to 50.3%) overall, 37.5% (95% CI, 8.5% to 75.5%) in previously untreated patients, and 37.0% (24.3% to 51.3%) in previously treated patients. Median progression-free survival was 6.5 months (95% CI, 5.2 to 9.0 months), and median overall survival was 15.4 months (95% CI, 9.6 to 22.8 months). The most common all-grade adverse event was nausea (40%). The safety profile of vemurafenib was similar to that observed in melanoma studies. CONCLUSION Vemurafenib showed promising activity in patients with NSCLC harboring BRAF V600 mutations. The safety profile of vemurafenib was similar to previous observations in patients with melanoma. Our results suggest a role for single-agent BRAF inhibition in patients with NSCLC and BRAF V600 mutations. Copyright © 2019 American Society of Clinical Oncology. All rights reserved. |
| Keywords: | adult; cancer survival; treatment outcome; treatment response; aged; middle aged; young adult; gene mutation; major clinical study; overall survival; fatigue; cancer growth; diarrhea; drug dose reduction; drug efficacy; drug safety; systemic therapy; progression free survival; drug eruption; phase 2 clinical trial; anemia; nausea; vomiting; cohort analysis; kidney failure; hyperkeratosis; arthralgia; asthenia; dyspnea; fever; pneumonia; lung embolism; acute kidney failure; survival time; multicenter study; seborrheic keratosis; sepsis; open study; skin papilloma; alopecia; b raf kinase; photosensitivity; chronic kidney failure; bronchitis; dysgeusia; respiratory failure; non small cell lung cancer; decreased appetite; pigmented nevus; acute coronary syndrome; vemurafenib; darier disease; lower respiratory tract infection; oropharynx candidiasis; very elderly; human; male; female; priority journal; article; treatment response time |
| Journal Title: | JCO Precision Oncology |
| Volume: | 3 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2019-06-27 |
| Language: | English |
| DOI: | 10.1200/po.18.00266 |
| PROVIDER: | scopus |
| PMCID: | PMC7446432 |
| PUBMED: | 32914022 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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