Our objective was to assess the comparative effectiveness and tolerability of all second-line treatments for advanced NSCLC with wild-type or unknown status for EGFR by a systematic review and network meta-analysis....For PFS, erlotinib plus cabozantinib was more effective than docetaxel (HR 0.39, 95% CrI 0.18–0.84), pemetrexed (0.38, 0.18–0.82), erlotinib (0.37, 0.18–0.78), and gefitinib (0.38, 0.18–0.82). Cabozantinib and pemetrexed plus erlotinib were also significantly more effective than the four recommended treatments.

Compared with erlotinib alone (median 1·8 months [95% CI 1·7–2·2]), progression-free survival was significantly improved in the cabozantinib group (4·3 months [3·6–7·4]; hazard ratio [HR] 0·39, 80% CI 0·27–0·55; one-sided p=0·0003) and in the erlotinib plus cabozantinib group (4·7 months [2·4–7·4]; HR 0·37, 0·25–0·53; one-sided p=0·0003)....in patients with EGFR wild-type NSCLC, cabozantinib alone or combined with erlotinib has clinically meaningful, superior efficacy to that of erlotinib alone...