Hot Paper in Medicine

November 2013
"Improved survival with vemurafenib in melanoma with BRAF V600E mutation," by P.B. Chapman and 27 others (for the BRIM-3 Study Group), New England Journal of Medicine, 364(26): 2507-17, 2011.

Abstract: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.”

This 2011 report from the New England Journal of Medicine was cited 110 times in current journal articles indexed by Thomson Reuters during May-June 2013. Thanks to that bimonthly tally, this currently ranks as the most-cited medicine paper published in the last two years, aside from reviews. Prior to the most recent two-month count, citations to the paper have accrued as follows:

March-April 2013: 101 citations
January-February 2013: 81
November-December 2012: 121
September-October 2012: 81
July-August 2012: 55
May-June 2012: 78
March-April 2012: 102
January-February 2012: 64
November-December 2011: 21
September-October 2011: 22
July-August 2011: 3

Total citations to date: 839

SOURCE: Thomson Reuters Web of Science

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.