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Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation
Open accessAbstract
BACKGROUND: Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. METHODS: We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. RESULTS: At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. CONCLUSIONS: Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).
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“Vemurafenib, a selective oral inhibitor of the BRAF V600 kinase, achieved an approximately 50% response and improved survival among metastatic melanoma patients with the BRAF V600E mutation [97].”
From Resistance to anti-EGFR therapies in metastatic colorectal cancer: underlying mechanisms and reversal strategies (2021) · cites this paper as [97]
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“Maturation of survival data also increased the ESMO-MCBS score of vemurafenib in the treatment of metastatic melanoma [116, 117] from ESMO-MCBS 3 based on PFS to 4, based on OS.”
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Cites
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Self-citationJemal, A., Siegel, R., Xu, J., & Ward, E. (2010) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20073 · Cited by 12,596
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Final Version of 2009 AJCC Melanoma Staging and Classification
Balch, C. M., Gershenwald, J. E., Soong, S.-J., Thompson, J. F., Atkins, M. B., Byrd, D. R., Buzaid, A. C., Cochran, A. J., Coit, D. G., Ding, S., et al. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.4799 · Cited by 4,653
Self-citationInhibition of Mutated, Activated BRAF in Metastatic Melanoma
Flaherty, K. T., Puzanov, I., Kim, K. B., Ribas, A., McArthur, G. A., Sosman, J. A., O'Dwyer, P. J., Lee, R. J., Grippo, J. F., Nolop, K., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1002011 · Cited by 3,103
Self-citationDistinct Sets of Genetic Alterations in Melanoma
Curtin, J. A., Fridlyand, J., Kageshita, T., Patel, H. N., Busam, K. J., Kutzner, H., Cho, K.-H., Aiba, S., Bröcker, E.-B., LeBoit, P. E., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050092 · Cited by 2,747
Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation
Nazarian, R., Shi, H., Wang, Q., Kong, X., Koya, R. C., Lee, H., Chen, Z., Lee, M., Attar, N., Sazegar, H., et al. (2010) · Nature · doi:10.1038/nature09626 · Cited by 2,244
Self-citationClinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma
Bollag, G. E., Hirth, P., Tsai, J. Y., Zhang, J., Ibrahim, P. N., Cho, H., Spevak, W. R., Zhang, C., Zhang, Y., Habets, G. G. M., et al. (2010) · Nature · doi:10.1038/nature09454 · Cited by 1,875
Self-citationRAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF
Poulikakos, P. I., Zhang, C., Bollag, G. E., Shokat, K. M., & Rosen, N. X. (2010) · Nature · doi:10.1038/nature08902 · Cited by 1,841
RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth
Hatzivassiliou, G., Song, K. W., Yen, I., Brandhuber, B. J., Anderson, D. J., Alvarado, R., Ludlam, M. J. C., Stokoe, D., Gloor, S. L., Vigers, G. P. A., et al. (2010) · Nature · doi:10.1038/nature08833 · Cited by 1,649
Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF
Heidorn, S. J., Milagre, C. S., Whittaker, S. R., Nourry, A., Niculescu‐Duvaz, I., Dhomen, N. S., Hussain, J., Reis-Filho, J. S., Springer, C. J., Pritchard, C. A., et al. (2010) · Cell · doi:10.1016/j.cell.2009.12.040 · Cited by 1,497
COT drives resistance to RAF inhibition through MAP kinase pathway reactivation
Johannessen, C. M., Boehm, J. S., Kim, S. Y., Thomas, S. R., Wardwell, L., Johnson, L. A., Emery, C. M., Stransky, N., Cogdill, A. P., Barretina, J., et al. (2010) · Nature · doi:10.1038/nature09627 · Cited by 1,460
Self-citationDiscovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity
Tsai, J., Lee, J. T., Wang, W., Zhang, J., Cho, H., Mamo, S., Bremer, R., Gillette, S., Kong, J., Haass, N. K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711741105 · Cited by 1,346
Villanueva, J., Vultur, A., Lee, J. T., Somasundaram, R., Fukunaga‐Kalabis, M., Cipolla, A. K., Wubbenhorst, B. S., Xu, X., Gimotty, P. A., Kee, D., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2010.11.023 · Cited by 1,289
Self-citationMiddleton, M. R., Grob, J., Aaronson, N. K., Fierlbeck, G., Tilgen, W., Seiter, S., Gore, M. E., Aamdal, S., Cebon, J. S., Coates, A., et al. (2000) · Journal of Clinical Oncology · doi:10.1200/jco.2000.18.1.158 · Cited by 1,270
Self-citationPrognostic and Clinicopathologic Associations of Oncogenic BRAF in Metastatic Melanoma
Long, G. V., Menzies, A. M., Nagrial, A. M., Haydu, L. E., Hamilton, A. L., Mann, G. J., Hughes, M., Thompson, J. F., Scolyer, R. A., & Kefford, R. F. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.32.4327 · Cited by 1,048
Chapman, P. B., Einhorn, L. H., Meyers, M. L., Saxman, S. B., Destro, A. N., Panageas, K. S., Begg, C. B., Agarwala, S. S., Schuchter, L. M., Ernstoff, M. S., et al. (1999) · Journal of Clinical Oncology · doi:10.1200/jco.1999.17.9.2745 · Cited by 763
Self-citationBedikian, A. Y., Millward, M. J., Pehamberger, H., Conry, R. M., Gore, M. E., Trefzer, U., Pavlick, A. C., DeConti, R. C., Hersh, E. M., Hersey, P., et al. (2006) · Journal of Clinical Oncology · doi:10.1200/jco.2006.06.0483 · Cited by 600
Self-citationSurvival plots of time-to-event outcomes in clinical trials: good practice and pitfalls
Pocock, S., Clayton, T. C., & Altman, D. G. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08594-x · Cited by 509
Avril, M.-F., Aamdal, S., Grob, J., Hauschild, A., Mohr, P., Bonerandi, J. J., Weichenthal, M., Neuber, K., Bieber, T. R. M., Gilde, K., et al. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.04.165 · Cited by 486
Self-citationJoseph, E. W., Pratilas, C. A., Poulikakos, P. I., Tadi, M., Wang, W., Taylor, B. S., Halilovic, E., Persaud, Y., Xing, F., Viale, A. J., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008990107 · Cited by 446
Self-citationArozarena, I., Sánchez‐Laorden, B. L., Packer, L., Hidalgo-Carcedo, C., Hayward, R., Virós, A., Sahai, E. A., & Marais, R. (2011) · Cancer Cell · doi:10.1016/j.ccr.2010.10.029 · Cited by 218
BRAF mutations in metastatic melanoma: a possible association with clinical outcome.
Kumar, R., Angelini, S., Czene, K., Sauroja, I., Hahka‐Kemppinen, M., Pyrhönen, S. O., & Hemminki, K. (2003) · PubMed · Cited by 205
Ribas, A., Kim, K. B., Schuchter, L. M., González, R., Pavlick, A. C., Weber, J. S., McArthur, G. A., Hutson, T. E., Flaherty, K. T., Moschos, S. J., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.8509 · Cited by 130
Self-citationThe histologic spectrum of epithelial neoplasms induced by sorafenib
Kwon, E. J., Kish, L. S., & Jaworsky, C. (2009) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2008.10.043 · Cited by 55
Sorafenib‐induced premalignant and malignant skin lesions
Williams, V. L., Cohen, P. R., & Stewart, D. J. (2011) · International Journal of Dermatology · doi:10.1111/j.1365-4632.2010.04822.x · Cited by 36
Wolchok, J. D., Thomas, L., Bondarenko, I., O'Day, S. J., Weber, J. S., Garbe, C., Francis, S., Ibrahim, R. A., Hoos, A., & Robert, C. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.15_suppl.lba5 · Cited by 21
Self-citationWolchok, J. D., Thomas, L., Bondarenko, I. N., O'Day, S. J., Weber, J. S., Garbe, C., Francis, S., Ibrahim, R. A., Hoos, A., & Robert, C. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.29.18_suppl.lba5 · Cited by 13
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- Kumar R, 2003, Clin Cancer Res, 9, 3362
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Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma
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Metadata
- Authors
- Chapman, P. B., Hauschild, A., Robert, C., Haanen, J. B., Ascierto, P., Larkin, J., Dummer, R., Garbe, C., Testori, A., Maio, M., Hogg, D., Lorigan, P., Lebbe, C., Jouary, T., Schadendorf, D., Ribas, A., O'Day, S. J., Sosman, J. A., Kirkwood, J. M., Eggermont, A. M. M., Dreno, B., Nolop, K., Li, J., Nelson, B., Hou, J., Lee, R. J., Flaherty, K. T., & McArthur, G. A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Christian-Albrechts-Universität zu Kiel (DE)
- Institut Gustave Roussy (FR)
- The Netherlands Cancer Institute (NL)
- Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT)
- Royal Marsden Hospital (GB)
- University of Zurich (CH)
- University of Tübingen (DE)
- European Institute of Oncology (IT)
- Tumour Institute of Tuscany (IT)
- University Health Network (CA)
- University of Manchester (GB)
- Hôpital Saint-André (FR)
- Essen University Hospital (DE)
- University of California, Los Angeles (US)
- Angeles Clinic and Research Institute (US)
- Vanderbilt University (US)
- University of Pittsburgh (US)
- Plexxikon (United States) (US)
- Genentech (US)
- Massachusetts General Hospital (US)
- Peter MacCallum Cancer Centre (AU)
- ORCID
- Chapman, Paul B.
- Hauschild, Axel
- Robert, Caroline
- Haanen, John B.
- Ascierto, Paolo
- Larkin, James
- Dummer, Reinhard
- Garbe, Claus
- Testori, Alessandro
- Maio, Michele
- Hogg, David
- Lorigan, Paul
- Jouary, Thomas
- Schadendorf, Dirk
- Ribas, Antoni
- O'Day, Steven J.
- Sosman, Jeffrey A.
- Kirkwood, John M.
- Eggermont, Alexander M.M.
- Li, Jiang
- Hou, Jeannie
- Lee, Richard J.
- Flaherty, Keith T.
- McArthur, Grant A.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2011-06-30
- Volume
- 364
- Issue
- 26
- Pages
- 2507-2516
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC3549296
- OpenAlex
- W2128542677
- Cited by
- 7,720
- References
- 28
- Citations by year
- 2026: 141 · 2025: 187 · 2024: 265 · 2023: 276 · 2022: 401 · 2021: 377 · 2020: 423 · 2019: 470 · 2018: 496 · 2017: 613 · 2016: 660 · 2015: 829 · 2014: 844 · 2013: 865 · 2012: 693
- FWCI
- 332.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Research Explorer (The University of Manchester) (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- PubMed Central (acceptedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health (UL1TR000005)
- National Cancer Institute (K24CA097588)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Keywords
- vemurafenib, dacarbazine, metastatic melanoma, BRAF V600E mutation, BRAF inhibitors, overall survival, progression-free survival, drug toxicity, keratoacanthoma, photosensitivity
- MeSH terms
- Vemurafenib, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Dacarbazine, Female, Humans, Indoles, Male, Melanoma, Middle Aged, Mutation, Sulfonamides, Survival Analysis, Disease-Free Survival, Proto-Oncogene Proteins B-raf, Young Adult, Intention to Treat Analysis
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