Dabrafenib-Trametinib Combination Shows Anti-Tumour Activity in Untreated, Mutation-Positive, Metastatic NSCLC
By Jenny Powers
MADRID, Spain -- September 13, 2017 -- Seventy-five percent of patients with previously untreated BRAFV600E-mutated non-small-cell lung cancer (NSCLC) can achieve complete or partial response or stable disease after receiving a combination of dabrafenib plus trametinib, according to findings from a phase 2 trial presented at the 42nd European Society for Medical Oncology (ESMO) Congress.
“Combined dabrafenib and trametinib represents a new targeted therapy with clinically meaningful anti-tumour activity and a manageable safety profile in patients with previously untreated BRAFV600E-mutated metastatic NSCLC,” noted lead author David Planchard, MD, PhD, Institut Gustave Roussy, Villejuif, France, speaking here at a late-breaker presentation on September 9.
At a median follow-up of 15.9 months, the primary endpoint of investigator-assessed overall response rate (ORR) was 64% (95% confidence interval [CI]: 46% to 79%). Two patients (6%) receiving the combination experienced a complete response (CR), and 21 (58%) patients demonstrated partial response (PR). Overall, 4 patients (11%) had stable disease (SD) lasting ≥ 12 weeks as their best response, offering a disease-control rate (DCR = CR+PR+SD) of 75% (95% CI: 58% to 88%).
An assessment by an independent review committee supported these results.
Dr. Planchard presented the results of the third (cohort C) of 3 sequentially enrolled cohorts in a study of patients with BRAFV600E-mutated metastatic NSCLC. In this cohort, 36 such patients received first-line treatment with 150 mg twice daily of dabrafenib and 2 mg once daily of trametinib. The patients had not received prior systemic therapy for metastatic disease.
At data cut-off on April 8, 2017, 11 patients (31%) remained on treatment.
The investigator-assessed median duration of response was 10.4 months (95% CI: 8.3 to 17.9 months). The median PFS was 10.9 months (95% CI: 7.0 to16.6 months) and median OS was 24.6 months (95% CI: 12.3 months to “not estimable”).
All patients experienced 1 or more adverse event (AE), and 69% had 1 or more grade 3/4 AE. Serious AEs occurring in more than 2 patients included alanine aminotransferase increase in 14%, pyrexia in 11%, aspartate aminotransferase increase in 8%, and ejection-fraction decrease in 8%.
A total of 24 patients progressed; of these, 17 patients died. One patient death was due to a serious AE of cardiorespiratory arrest, which was unrelated to study treatment.
Patients in this study cohort had a median age of 67 years (range: 44 to 91 years), 61% were female, 83% were white, and 72% were current or former smokers.
In patients with BRAF-mutated metastatic melanoma, combined BRAF and MEK inhibition has shown superior efficacy compared with BRAF inhibitor monotherapy, Dr. Planchard noted, potentially contributing to sustained pathway inhibition and delay or prevention of resistance.
Funding for this study was provided by Novartis, Basel, Switzerland.
[Presentation title: Phase 2 Trial (BRF113928) of Dabrafenib (D) Plus Trametinib (T) in Patients (pts) With Previously Untreated BRAF V600E–Mutant Metastatic Non-Small Cell Lung Cancer (NSCLC). Abstract LBA51]