Reference Detail

Ref Type

Journal Article

PMID

(32029534)

Authors

Subbiah V, Puzanov I, Blay JY, Chau I, Lockhart AC, Raje NS, Wolf J, Baselga J, Meric-Bernstam F, Roszik J, Diamond EL, Riely GJ, Sherman EJ, Riehl T, Pitcher B, Hyman DM

Title

Pan-Cancer Efficacy of Vemurafenib in BRAFV600-Mutant Non-Melanoma Cancers.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer discovery	10	5	2020 May	657-663	Cancer Discov

URL

Abstract Text

BRAFV600 mutations occur in a wide range of tumor types, and RAF inhibition has become standard in several of these cancers. Despite this progress, BRAFV600 mutations have historically been considered a clear demonstration of tumor lineage context-dependent oncogene addiction, based predominantly on the insensitivity to RAF inhibition in colorectal cancer. However, the true broader activity of RAF inhibition pan-cancer remains incompletely understood. To address this, we conducted a multicohort "basket" study of the BRAF inhibitor vemurafenib in non-melanoma BRAFV600 mutation-positive solid tumors. In total, 172 patients with 26 unique cancer types were treated, achieving an overall response rate of 33% and median duration of response of 13 months. Responses were observed in 13 unique cancer types, including historically treatment-refractory tumor types such as cholangiocarcinoma, sarcoma, glioma, neuroendocrine carcinoma, and salivary gland carcinomas. Collectively, these data demonstrate that single-agent BRAF inhibition has broader clinical activity than previously recognized. SIGNIFICANCE: These data suggest that BRAFV600 mutations lead to oncogene addiction and are clinically actionable in a broad range of non-melanoma cancers, including tumor types in which RAF inhibition is not currently considered standard of care.See related commentary by Ribas and Lo, p. 640.This article is highlighted in the In This Issue feature, p. 627.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600E	neuroendocrine carcinoma	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in patients with neuroendocrine carcinoma harboring BRAF V600E (n=3) when treated with Zelboraf (vemurafenib), including 1 patient with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	ovarian cancer	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in ovarian cancer patients harboring BRAF V600E (n=4) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	salivary gland cancer	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), a patient with salivary ductal carcinoma harboring BRAF V600E demonstrated a partial response when treated with Zelboraf (vemurafenib) (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	cholangiocarcinoma	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in patients with cholangiocarcinoma harboring BRAF V600E (n=9) when treated with Zelboraf (vemurafenib), including 2 patients with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	high grade glioma	sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in glioma patients harboring BRAF V600E (n=24) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 5 patients with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	Advanced Solid Tumor	sensitive	Vemurafenib	Phase II	Actionable	In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in an objective response rate of 33% (56/172) in patients with advanced solid tumors harboring BRAF V600E, including 5 patients with a complete response and 51 patients with a partial response, and led a duration of response of 13.1 months, a progression-free survival of 5.8 months, and an overall survival of 17.6 months (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	sarcoma	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in sarcoma patients harboring BRAF V600E (n=6) when treated with Zelboraf (vemurafenib), including 1 patient with a complete response and 1 patient with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	lung non-small cell carcinoma	sensitive	Vemurafenib	Phase II	Actionable	In a Phase II trial (VE-BASKET), responses were seen in patients with non-small cell lung cancer harboring BRAF V600E (n=63) when treated with Zelboraf (vemurafenib), including 23 patients with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	anaplastic thyroid carcinoma	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), Zelboraf (vemurafenib) treatment resulted in a response in patients with anaplastic thyroid carcinoma harboring BRAF V600E (n=12), including 1 patient with a complete response and 2 patients with a partial response (PMID: 32029534; NCT01524978).	32029534
BRAF V600E	histiocytic and dendritic cell cancer	predicted - sensitive	Vemurafenib	Case Reports/Case Series	Actionable	In a Phase II trial (VE-BASKET), responses were seen in patients with histiocytic neoplasms harboring BRAF V600E (n=27) when treated with Zelboraf (vemurafenib), including 15 patients with a partial response and 2 patients with a complete response (PMID: 32029534; NCT01524978).	32029534