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Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Publication ,  Conference
Meric-Bernstam, F; Rothe, M; Mangat, PK; Garrett-Mayer, E; Gutierrez, R; Ahn, ER; Cannon, TL; Powell, S; Krauss, JC; Reynolds, CM; Behl, D ...
Published in: JCO Precis Oncol
September 2023

PURPOSE: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. The results in a cohort of patients with solid tumors with BRAF mutations treated with cobimetinib plus vemurafenib are reported. METHODS: Eligible patients had measurable disease (RECIST v.1.1), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as complete response (CR) or partial response (PR) or stable disease of at least 16-weeks duration (SD16+). Low-accruing histology-specific cohorts with BRAF mutations treated with cobimetinib plus vemurafenib were collapsed into a single histology-pooled cohort for this analysis. The results were evaluated on the basis of a one-sided exact binomial test with a null DC rate of 15% versus 35% (power, .82; α, .10). The secondary end points were objective response (OR), progression-free survival, overall survival, duration of response, duration of stable disease, and safety. RESULTS: Thirty-one patients with solid tumors with BRAF mutations were enrolled. Twenty-eight patients were evaluable for efficacy. Patients had tumors with BRAF V600E (n = 26), K601E (n = 2), or other (n = 3) mutations. Two patients with CR (breast and ovarian cancers; V600E), 14 with PR (13 V600E, one N581I), and three with SD16+ (two V600E, one T599_V600insT) were observed with a DC rate of 68% (P < .0001; one-sided 90% CI, 54 to 100) and an OR rate of 57% (95% CI, 37 to 76). Nineteen patients experienced ≥one drug-related grade 3-5 adverse event or serious adverse event including one death attributed to treatment-related kidney injury. CONCLUSION: Cobimetinib plus vemurafenib showed antitumor activity in patients with advanced solid tumors with BRAF V600E mutations; additional study is warranted to confirm the antitumor activity in tumors with non-V600E BRAF mutations.

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Published In

JCO Precis Oncol

DOI

EISSN

2473-4284

Publication Date

September 2023

Volume

7

Start / End Page

e2300385

Location

United States

Related Subject Headings

  • Vemurafenib
  • Proto-Oncogene Proteins B-raf
  • Mutation
  • Melanoma
  • Humans
  • Antineoplastic Agents
  • 3211 Oncology and carcinogenesis
 

Citation

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Meric-Bernstam, F., Rothe, M., Mangat, P. K., Garrett-Mayer, E., Gutierrez, R., Ahn, E. R., … Schilsky, R. L. (2023). Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. In JCO Precis Oncol (Vol. 7, p. e2300385). United States. https://doi.org/10.1200/PO.23.00385
Meric-Bernstam, Funda, Michael Rothe, Pam K. Mangat, Elizabeth Garrett-Mayer, Rodolfo Gutierrez, Eugene R. Ahn, Timothy L. Cannon, et al. “Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.” In JCO Precis Oncol, 7:e2300385, 2023. https://doi.org/10.1200/PO.23.00385.
Meric-Bernstam F, Rothe M, Mangat PK, Garrett-Mayer E, Gutierrez R, Ahn ER, et al. Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. In: JCO Precis Oncol. 2023. p. e2300385.
Meric-Bernstam, Funda, et al. “Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.JCO Precis Oncol, vol. 7, 2023, p. e2300385. Pubmed, doi:10.1200/PO.23.00385.
Meric-Bernstam F, Rothe M, Mangat PK, Garrett-Mayer E, Gutierrez R, Ahn ER, Cannon TL, Powell S, Krauss JC, Reynolds CM, von Mehren M, Behl D, Calfa CJ, Duvivier HL, Kaplan HG, Livingston MB, Sharma MR, Urba WJ, Grantham GN, Hinshaw DC, Gregory A, Halabi S, Schilsky RL. Cobimetinib Plus Vemurafenib in Patients With Solid Tumors With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study. JCO Precis Oncol. 2023. p. e2300385.

Published In

JCO Precis Oncol

DOI

EISSN

2473-4284

Publication Date

September 2023

Volume

7

Start / End Page

e2300385

Location

United States

Related Subject Headings

  • Vemurafenib
  • Proto-Oncogene Proteins B-raf
  • Mutation
  • Melanoma
  • Humans
  • Antineoplastic Agents
  • 3211 Oncology and carcinogenesis