Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E

Sigrun Hallmeyer, Rene Gonzalez, David H. Lawson, Lee D. Cranmer, Gerald P. Linette, Igor Puzanov, Bret Taback, C. Lance Cowey, Antoni Ribas, Gregory A. Daniels, Timothy Moore, Geoffrey T. Gibney, Hussein Tawbi, Eric Whitman, Geraldine Lee, Yong Mun, Shiyao Liu, Omid Hamid

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

BRAF mutations are found in ~ 50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAFV600E-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety. Planned (V600K vs. non-V600K mutations) subgroup analyses were carried out. Thirty-one patients were enrolled; 13 (42%) had V600K mutations and 18 (58%) had other mutations. Investigator-assessed confirmed that the best overall response rate was 23% (95% confidence interval=10-41%) in the overall population, and was similar between patients with V600K mutations (23%; 95% confidence interval=5-54%) versus other mutations (22%; 95% confidence interval=6-48%). Responses were observed in patients with V600K (n=3), V600E2 (n=1), V600R (n=1), L597S (n=1) and D594G (n=1) mutations. No new safety signals were reported. Vemurafenib showed activity in patients with advanced melanoma with rarer BRAF mutations.

Original languageEnglish (US)
Pages (from-to)585-590
Number of pages6
JournalMelanoma Research
Volume27
Issue number6
DOIs
StatePublished - Jan 1 2017

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Exons
Melanoma
Mutation
Therapeutics
Confidence Intervals
Disease-Free Survival
Research Personnel
PLX4032
Safety
Survival
Codon
Population

All Science Journal Classification (ASJC) codes

  • Oncology
  • Dermatology
  • Cancer Research

Cite this

Hallmeyer, Sigrun ; Gonzalez, Rene ; Lawson, David H. ; Cranmer, Lee D. ; Linette, Gerald P. ; Puzanov, Igor ; Taback, Bret ; Cowey, C. Lance ; Ribas, Antoni ; Daniels, Gregory A. ; Moore, Timothy ; Gibney, Geoffrey T. ; Tawbi, Hussein ; Whitman, Eric ; Lee, Geraldine ; Mun, Yong ; Liu, Shiyao ; Hamid, Omid. / Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E. In: Melanoma Research. 2017 ; Vol. 27, No. 6. pp. 585-590.
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title = "Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E",
abstract = "BRAF mutations are found in ~ 50{\%} of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAFV600E-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety. Planned (V600K vs. non-V600K mutations) subgroup analyses were carried out. Thirty-one patients were enrolled; 13 (42{\%}) had V600K mutations and 18 (58{\%}) had other mutations. Investigator-assessed confirmed that the best overall response rate was 23{\%} (95{\%} confidence interval=10-41{\%}) in the overall population, and was similar between patients with V600K mutations (23{\%}; 95{\%} confidence interval=5-54{\%}) versus other mutations (22{\%}; 95{\%} confidence interval=6-48{\%}). Responses were observed in patients with V600K (n=3), V600E2 (n=1), V600R (n=1), L597S (n=1) and D594G (n=1) mutations. No new safety signals were reported. Vemurafenib showed activity in patients with advanced melanoma with rarer BRAF mutations.",
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Hallmeyer, S, Gonzalez, R, Lawson, DH, Cranmer, LD, Linette, GP, Puzanov, I, Taback, B, Cowey, CL, Ribas, A, Daniels, GA, Moore, T, Gibney, GT, Tawbi, H, Whitman, E, Lee, G, Mun, Y, Liu, S & Hamid, O 2017, 'Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E', Melanoma Research, vol. 27, no. 6, pp. 585-590. https://doi.org/10.1097/CMR.0000000000000398

Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E. / Hallmeyer, Sigrun; Gonzalez, Rene; Lawson, David H.; Cranmer, Lee D.; Linette, Gerald P.; Puzanov, Igor; Taback, Bret; Cowey, C. Lance; Ribas, Antoni; Daniels, Gregory A.; Moore, Timothy; Gibney, Geoffrey T.; Tawbi, Hussein; Whitman, Eric; Lee, Geraldine; Mun, Yong; Liu, Shiyao; Hamid, Omid.

In: Melanoma Research, Vol. 27, No. 6, 01.01.2017, p. 585-590.

Research output: Contribution to journalArticle

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T1 - Vemurafenib treatment for patients with locally advanced, unresectable stage IIIC or metastatic melanoma and activating exon 15 BRAF mutations other than V600E

AU - Hallmeyer, Sigrun

AU - Gonzalez, Rene

AU - Lawson, David H.

AU - Cranmer, Lee D.

AU - Linette, Gerald P.

AU - Puzanov, Igor

AU - Taback, Bret

AU - Cowey, C. Lance

AU - Ribas, Antoni

AU - Daniels, Gregory A.

AU - Moore, Timothy

AU - Gibney, Geoffrey T.

AU - Tawbi, Hussein

AU - Whitman, Eric

AU - Lee, Geraldine

AU - Mun, Yong

AU - Liu, Shiyao

AU - Hamid, Omid

PY - 2017/1/1

Y1 - 2017/1/1

N2 - BRAF mutations are found in ~ 50% of metastatic melanomas, most commonly in codon V600. Vemurafenib improves progression-free survival and overall survival in patients with advanced BRAFV600E-mutated melanoma. The results of a descriptive study evaluating vemurafenib in patients with advanced melanoma harbouring BRAF mutations other than V600E are reported. Eligible patients with stage IIIC or IV melanoma and non-V600E BRAF mutations received vemurafenib (960 mg, twice daily). End points included investigator-assessed best overall response rate (primary), time to response, duration of response, progression-free survival, overall survival and safety. Planned (V600K vs. non-V600K mutations) subgroup analyses were carried out. Thirty-one patients were enrolled; 13 (42%) had V600K mutations and 18 (58%) had other mutations. Investigator-assessed confirmed that the best overall response rate was 23% (95% confidence interval=10-41%) in the overall population, and was similar between patients with V600K mutations (23%; 95% confidence interval=5-54%) versus other mutations (22%; 95% confidence interval=6-48%). Responses were observed in patients with V600K (n=3), V600E2 (n=1), V600R (n=1), L597S (n=1) and D594G (n=1) mutations. No new safety signals were reported. Vemurafenib showed activity in patients with advanced melanoma with rarer BRAF mutations.

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