Abstract
Due to the rarity of BRAF V600E mutation, no randomized study has compared the combination targeted therapy dabrafenib + trametinib with other second-line treatments for advanced or metastatic non-small-cell lung cancer (NSCLC). A network meta-analysis (NMA) was conducted to assess the comparative efficacy of treatments among patients with previously treated advanced or metastatic NSCLC. Randomized trials of dabrafenib + trametinib, docetaxel, erlotinib, nintedanib + docetaxel, nivolumab, pemetrexed, pembrolizumab, and best supportive care as second-line or above treatments for advanced or metastatic NSCLC identified in a systematic literature review were included in the NMA. Overall response rates (ORRs) and disease control rates (DCRs) were compared using logit models; progression-free survival (PFS) and overall survival (OS) were compared using fractional polynomial hazards models. Dabrafenib + trametinib was linked into the evidence network through a matching-adjusted indirect comparison versus nivolumab. Ten trials met the inclusion criteria and were included in the NMA. Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with the highest odds of achieving overall response (12.2, 1.2, and 0.7 times higher, respectively, compared with docetaxel). Estimated DCR was higher for dabrafenib + trametinib, nintedanib + docetaxel, and pemetrexed compared with other treatments. Patients treated with dabrafenib + trametinib, nivolumab, and pembrolizumab had the lowest hazards of disease progression or death during follow-up (72, 61, and 29% lower hazard of progression at 6months; 61, 48, and 46% lower hazard of death at 1year, respectively, compared with docetaxel). Dabrafenib + trametinib, pembrolizumab, and nivolumab were associated with higher ORR and prolonged PFS and OS compared with chemotherapy in previously treated advanced or metastatic NSCLC. Novartis Pharmaceuticals Corporation.
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