Matching-Adjusted Indirect Comparison (MAIC) of Dabrafenib Plus Trametinib Versus Pembrolizumab Plus Chemotherapy in Patients with Treatment-Naive Metastatic BRAF V600 Mutation-Positive Non-Small Cell Lung Cancer (NSCLC)

OBJECTIVES: There is a large unmet need for the treatment of metastatic non-small cell lung cancer (NSCLC) patients harbouring the BRAF V600 mutation. The efficacy of dabrafenib with trametinib (Taf-Mek) for the treatment naive metastatic BRAF V600 mutated NSCLC was assessed in the single arm phase II BRF113928 trial (NCT1033634). In the absence of a head-to-head study, an unanchored MAIC was conducted to compare overall survival (OS) and progression-free survival (PFS) with pembrolizumab plus platinum-based chemotherapy (Pembro+PDC).

METHODS: Individual patient data (IPD) from Cohort C of the BRF113928 trial (NCT01336634) were weighted to match the aggregate baseline characteristics of the Pembro+PDC arm from the KEYNOTE-189 trial (NCT02578680). The prognostic variables were selected based on literature and Cox-regression analysis, and included age, gender, ECOG, smoking status, histology, liver metastases, brain metastases and extent of metastasis. Pseudo IPD of Pembro+PDC was obtained by digitizing Kaplan-Meier (KM) curves and the Guyot algorithm. After matching, hazard ratios (HRs) were estimated using a weighted Cox proportional hazard model. Success of matching was assessed by inspecting distributions of weights and effective sample size (ESS).

RESULTS: The MAIC successfully balanced reported baseline characteristics. Before matching, OS was similar between Taf-Mek and Pembro+PDC (HR 0.944 [95% CI 0.638 - 1.398]) while adjusted HR numerically favored Taf-Mek (HR 0.817 [95% CI 0.454 - 1.471]). Taf-Mek appeared to prolong PFS compared with Pembro+PDC both before and after matching but the difference was not significant (naive HR 0.759 [95% CI 0.493 - 1.167]; adjusted HR 0.842 [95% CI 0.295 - 2.402]).

CONCLUSIONS: The MAIC showed that Taf-Mek has numerically better OS and PFS than Pembro+PDC in treatment-naive metastatic BRAF V600 mutation-positive NSCLC patients; however results are not statistically significant. A limitation of this study is that it was not possible to match for BRAF mutation and PD-L1.