Dabrafenib and trametinib

In a phase II, multicenter, nonrandomized, open-label study (NCT01336634), 57 patients with progression after at least one to three previous platinum-containing regimens for treatment of metastatic NSCLC, who tested positive for BRAF V600E variants, were treated with dabrafenib (a BRAF inhibitor) 150 mg twice a day and trametinib (a MEK inhibitor) 2 mg every day.[40] BRAF V600E variants were ascertained by local testing. The primary end point was investigator-assessed overall response.

In a phase II, multicenter, nonrandomized, open-label study (NCT01336634), 57 patients with progression after at least one to three previous platinum-containing regimens for treatment of metastatic NSCLC, who tested positive for BRAF V600E variants, were treated with dabrafenib (a BRAF inhibitor) 150 mg twice a day and trametinib (a MEK inhibitor) 2 mg every day.[40] BRAF V600E variants were ascertained by local testing. The primary end point was investigator-assessed overall response.

The overall response rate was 63.2% (95% CI, 49.3%–75.6%), as determined independently by investigator and independent review committee assessments. There were 2 out of 36 complete responses by investigator assessment; all responses were deemed partial by the independent review committee.

In a phase II, multicenter, nonrandomized, open-label study (NCT01336634), 57 patients with progression after at least one to three previous platinum-containing regimens for treatment of metastatic NSCLC, who tested positive for BRAF V600E variants, were treated with dabrafenib (a BRAF inhibitor) 150 mg twice a day and trametinib (a MEK inhibitor) 2 mg every day.[40] BRAF V600E variants were ascertained by local testing. The primary end point was investigator-assessed overall response.

The median investigator-assessed PFS was 9.7 months (95% CI, 6.9–19.6 months). The estimated median DOR was 9.0 months (95% CI, 6.9–18.3). The OS data are immature.

In a phase II, multicenter, nonrandomized, open-label study (NCT01336634), 57 patients with progression after at least one to three previous platinum-containing regimens for treatment of metastatic NSCLC, who tested positive for BRAF V600E variants, were treated with dabrafenib (a BRAF inhibitor) 150 mg twice a day and trametinib (a MEK inhibitor) 2 mg every day.[40] BRAF V600E variants were ascertained by local testing. The primary end point was investigator-assessed overall response.

Forty-nine percent of patients had at least one grade 3 or 4 adverse event, the most common of which were neutropenia, hyponatremia, and anemia.[40][Level of evidence C3]