Dabrafenib plus trametinib shows promise over docetaxel for BRAF-mutated NSCLC
CHICAGO — Combination therapy with dabrafenib and trametinib conferred longer survival than docetaxel for patients with BRAF V600E-positive non-small cell lung cancer, according to results of an adjusted indirect comparison presented at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
“In the absence of head-to-head trials, indirect comparisons of the efficacy of novel targeted therapy vs. standard of care can provide valuable evidence to inform clinical and economic decision-making,” Medha Sasane, from Novartis Oncology, said during his presentation.
Novel targeted therapy dabrafenib (Tafinlar, GlaxoSmithKline) — a BRAF inhibitor — in combination with trametinib (Mekinist, GlaxoSmithKline), a MEK inhibitor, have expanded treatment options for metastatic BRAF V600E-mutant NSCLC.
However, randomized clinical trials comparing the combination regimen with current standard of care, docetaxel, are absent because the BRAF V600E mutation is rare in this population.
Therefore, Sasane and colleagues conducted a matching-adjusted indirect comparison to understand comparative efficacy of dabrafenib plus trametinib vs. docetaxel.
Researchers used two studies — NCT03133634 and CheckMate 057 — that had similar inclusion/exclusion criteria for comparison. The studies also both used RECIST v1.1 to evaluate response to therapy.
The analysis included 290 patients from CheckMate 057 who had locally advanced squamous cell lung cancer and an ECOG score of 0 to 1 who received docetaxel. In NCT03133634, 57 patients with metastatic BRAF-mutated adenocarcinoma lung cancer with an ECOG score of 0 to 2 received dabrafenib plus trametinib.
Both groups of patients received at least one prior platinum-based chemotherapy. Before matching, the two groups differed in terms of prior radiotherapy use (dabrafenib plus trametinib, 28% vs. docetaxel, 48%; P < .01) and receipt of at least two prior regimens (33% vs. 11%; P < .01).
Using propensity score weighting, researchers matched patient characteristics including age, gender, race, smoking history, ECOG score, tumor histology, prior regimens, prior radiotherapy and prior maintenance therapy.
Researchers compared PFS, OS, overall response rate and disease control rate for the patient populations.
Results showed patients who received dabrafenib plus trametinib vs. docetaxel demonstrated longer median PFS (9.7 months vs. 4.2 months; HR = 0.32; 95% CI, 0.26-0.4) and longer median OS (19.2 months vs. 9.3 months; HR = 0.41; 95% CI, 0.32-0.51).
Patients treated with dabrafenib plus trametinib also demonstrated a higher ORR (61% vs. 12%; P < .01) and disease control rate (77% vs. 55%; P < .01).
Sasane noted researchers adjusted multiple baseline characteristics for the comparison; therefore, there is a potential for bias due to unobserved or unmeasured confounding factors. Further, the researchers lacked data on patients’ BRAF mutation status in Checkmate 057, and survival data were immature survival data at the time of analysis. – by Melinda Stevens
Sasane M, et al. Abstract OA03.07. Presented at: International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology; Sept. 14-16, 2017; Chicago.
Disclosure: Sasane reports employment with Novartis Oncology.