Reference Detail

Ref Type

Journal Article

PMID

(36409971)

Authors

Klute KA, Rothe M, Garrett-Mayer E, Mangat PK, Nazemzadeh R, Yost KJ, Duvivier HL, Ahn ER, Cannon TL, Alese OB, Krauss JC, Thota R, Calfa CJ, Denlinger CS, O'Lone R, Halabi S, Grantham GN, Schilsky RL

Title

Cobimetinib Plus Vemurafenib in Patients With Colorectal Cancer With BRAF Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Journal	Vol	Issue	Date	Pages	Journal Short Title
JCO precision oncology	6		2022 Nov	e2200191	JCO Precis Oncol

URL

Abstract Text

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) with BRAF mutations treated with cobimetinib (C) plus vemurafenib (V) are reported.Eligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors with BRAF V600E/D/K/R mutations, and no MAP2K1/2, MEK1/2, or NRAS mutations. C was taken 60 mg orally once daily for 21 days followed by seven days off, and V was taken 960 mg orally twice daily. Simon's two-stage design was used with a primary study end point of objective response or stable disease of at least 16 weeks duration. Secondary end points were progression-free survival, overall survival, and safety.Thirty patients were enrolled from August 2016 to August 2018; all had CRC with a BRAF V600E mutation except one patient with a BRAF K601E mutation. Three patients were not evaluable for efficacy. Eight patients with partial responses and six patients with stable disease of at least 16 weeks duration were observed for disease control and objective response rates of 52% (95% CI, 35 to 65) and 30% (95% CI, 14 to 50), respectively. The null hypothesis of 15% disease control rate was rejected (P < .0001). Thirteen patients had at least one grade 3 adverse event or serious adverse event at least possibly related to C + V: anemia, decreased lymphocytes, dyspnea, diarrhea, elevated liver enzymes, fatigue, hypercalcemia, hypophosphatemia, rash, photosensitivity, and upper gastrointestinal hemorrhage.The combination of C + V has antitumor activity in heavily pretreated patients with CRC with BRAF mutations.

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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	colorectal cancer	sensitive	Cobimetinib + Vemurafenib	Phase II	Actionable	In a Phase II trial (TAPUR), the combination of Cotellic (cobimetinib) and Zelboraf (vemurafenib) resulted in an objective response rate of 30% (8/27; all partial responses), a disease control rate of 52% (14/27), a median progression-free survival of 15.7 weeks, and a median overall survival of 38.9 weeks in patients with colorectal cancer harboring BRAF V600E (n=26) or K601E (n=1) (PMID: 36409971; NCT02693535).	36409971