BRAF Mekinist (trametinib ) Tafinlar (dabrafenib)

Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H

In the November 20, 2020 edition of Journal of Clinical Oncology, April K. S. Salama and colleagues report on the results of the Subprotocol H (EAY131-H) of the NCI-MATCH platform trials.

BACKGROUND

Subprotocol H (EAY131-H) of the NCI-MATCH platform trial was organized to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors had evidence of a BRAFV600 mutation.

PATIENTS AND METHODS

EAY131-H was an open-label, single-arm study, where patients with melanoma, non-small cell lung cancer, colorectal cancer, or thyroid cancer were excluded; Patients were treated with dabrafenib 150 mg twice per day and trametinib 2 mg per day continuously until unbearable toxicity or disease progression . ORR was the primary endpoint. OS, 6m PFS and PFS were secondary endpoints.

RESULTS

29 of 35 patients who were enrolled were involved in the primary efficacy analysis.  Of these patients, the median age was 59 years, and 45% of the patients had received 3 or more lines of therapy. The confirmed overall response rate was 38% (90% CI, 22.9% to 54.9%) with P < .0001 against a null rate of 5%, and progression free survival was 11.4 months (90% CI, 8.4 to 16.3 months); responses were seen in 7 different tumor types. 7 patients had a duration of response of > 1 year, including 4 patients with a duration of response of > 2 years. An additional 8 patients had a progression free survival of more than 6 months. The median OS was 28.6 months.

The authors concluded “This study met its primary end point, with an ORR of 38% (P < .0001) in this mixed histology, pretreated cohort. This promising activity warrants additional investigations in BRAFV600-mutated tumors outside of currently approved indications.”

Reference:

Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H

https://ascopubs.org/doi/full/10.1200/JCO.20.00762

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