Dabrafenib plus trametinib demonstrated robust antitumor activity with a manageable safety profile in patients with BRAF V600E mutation-positive non-small cell lung cancer (NSCLC), a study published in the journal The Lancet Oncology has shown.1
The combination of dabrafenib and trametinib is approved by the U.S. Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations. Based on observations in melanoma, researchers sought to evaluate the antitumor activity and safety of the combination in patients with BRAF V600E-mutant NSCLC.
For the international, open-label, phase 2 trial, investigators enrolled 57 patients with pretreated metastatic stage IV disease who had documented disease progression after at least 1 previous platinum-based chemotherapy, and who had received no more than 3 prior systemic anticancer therapies. Patients with previous BRAF or MEK inhibitor treatment were ineligible to participate in the study.
All patients received dabrafenib 150 mg orally twice daily plus trametinib 2 mg orally once daily continuously in 21-day cycles until disease progression or unacceptable toxicity.
Results showed that 63.2% (95% CI, 49.3-75.6) achieved an overall response per investigator assessment.
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The most common grade 3 to 4 adverse events were neutropenia (9%), hyponatremia (4%), and anemia (5%). A total of 56% of patients reported serious adverse events, including pyrexia (16%), anemia (5%), confusional state, decreased appetite, hemoptysis, hypercalcemia, nausea, and cutaneous squamous cell carcinoma (each in 4%).
Four patients died due to fatal adverse events deemed unrelated to combination kinase inhibitor therapy.
- Planchard D, Besse B, Groen HJM, Souquet PJ, Quoix E, Balk CS, et al. Dabrafenib plus trametinib in patients with previously treated BRAFV600E-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial [published online ahead of print June 6, 2016]. Lancet Oncol. doi: 10.1016/S1470-2045(16)30146-2.