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

Publication ,  Journal Article
Salama, AKS; Li, S; Macrae, ER; Park, J-I; Mitchell, EP; Zwiebel, JA; Chen, HX; Gray, RJ; McShane, LM; Rubinstein, LV; Patton, D; Williams, PM ...
Published in: J Clin Oncol
November 20, 2020

PURPOSE: BRAFV600 mutations are commonly found in melanoma and thyroid cancers and to a lesser degree in other tumor types. Subprotocol H (EAY131-H) of the NCI-MATCH platform trial sought to investigate the selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumors, lymphomas, or multiple myeloma whose tumors harbored a BRAFV600 mutation. PATIENTS AND METHODS: EAY131-H is an open-label, single-arm study. Patients with melanoma, thyroid, or colorectal cancer were excluded; patients with non-small-cell lung cancer were later excluded in an amendment. Patients received dabrafenib 150 mg twice per day and trametinib 2 mg per day continuously until disease progression or intolerable toxicity. The primary end point was centrally assessed objective response rate (ORR); secondary end points included progression-free survival (PFS), 6-month PFS, and overall survival. RESULTS: Thirty-five patients were enrolled, and 29 were included in the primary efficacy analysis as prespecified in the protocol. Median age was 59 years, and 45% of the patients had received ≥ 3 lines of therapy. The confirmed ORR was 38% (90% CI, 22.9% to 54.9%) with P < .0001 against a null rate of 5%, and PFS was 11.4 months (90% CI, 8.4 to 16.3 months); responses were seen in 7 distinct tumor types. Seven patients had a duration of response of > 12 months, including 4 patients with a duration of response of > 24 months. An additional 8 patients had a PFS > 6 months. The median overall survival was 28.6 months. Reported adverse events were comparable to those noted in previously reported profiles of dabrafenib and trametinib. CONCLUSION: 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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 20, 2020

Volume

38

Issue

33

Start / End Page

3895 / 3904

Location

United States

Related Subject Headings

  • Young Adult
  • Pyrimidinones
  • Pyridones
  • Proto-Oncogene Proteins B-raf
  • Oximes
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Middle Aged
  • Male
 

Citation

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Salama, A. K. S., Li, S., Macrae, E. R., Park, J.-I., Mitchell, E. P., Zwiebel, J. A., … Flaherty, K. T. (2020). Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol, 38(33), 3895–3904. https://doi.org/10.1200/JCO.20.00762
Salama, April K. S., Shuli Li, Erin R. Macrae, Jong-In Park, Edith P. Mitchell, James A. Zwiebel, Helen X. Chen, et al. “Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H.J Clin Oncol 38, no. 33 (November 20, 2020): 3895–3904. https://doi.org/10.1200/JCO.20.00762.
Salama AKS, Li S, Macrae ER, Park J-I, Mitchell EP, Zwiebel JA, et al. Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol. 2020 Nov 20;38(33):3895–904.
Salama, April K. S., et al. “Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H.J Clin Oncol, vol. 38, no. 33, Nov. 2020, pp. 3895–904. Pubmed, doi:10.1200/JCO.20.00762.
Salama AKS, Li S, Macrae ER, Park J-I, Mitchell EP, Zwiebel JA, Chen HX, Gray RJ, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Armstrong DK, Conley BA, Arteaga CL, Harris LN, O’Dwyer PJ, Chen AP, Flaherty KT. Dabrafenib and Trametinib in Patients With Tumors With BRAFV600E Mutations: Results of the NCI-MATCH Trial Subprotocol H. J Clin Oncol. 2020 Nov 20;38(33):3895–3904.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

November 20, 2020

Volume

38

Issue

33

Start / End Page

3895 / 3904

Location

United States

Related Subject Headings

  • Young Adult
  • Pyrimidinones
  • Pyridones
  • Proto-Oncogene Proteins B-raf
  • Oximes
  • Oncology & Carcinogenesis
  • Neoplasms
  • Mutation
  • Middle Aged
  • Male