Erlotinib with bevacizumab showed promising activity in recurrent nonsquamous (NS) nonsmall cell lung cancer (NSCLC). The INNOVATIONS study was designed to assess in first-line treatment of unselected cisplatin-eligible patients this combination compared to cisplatin, gemcitabine and bevacizumab.

Stage IIIB/IV patients with NS-NSCLC were randomised on erlotinib (150 mg daily) and bevacizumab (15 mg·kg^–1 on day 1, every 3 weeks) (EB) until progression, or cisplatin (80 mg·m^–2 on day 1, every 3 weeks) and gemcitabine (1250 mg·m^–2 on days 1 and 8, every 3 weeks) up to six cycles and bevacizumab (15 mg·kg^–1 on day 1, every 3 weeks) (PGB) until progression.

224 patients were randomised (EB n=111, PGB n=113). The response rate (12% versus 36%; p<0.0001), progression-free survival (median 3.5 versus 6.9 months; hazard ratio (HR) 1.85, 95% CI 1.39–2.45; p<0.0001) and overall survival (median 12.6 versus 17.8 months; HR 1.41, 95% CI 1.01–1.97; p=0.04) clearly favoured PGB. In patients with epidermal growth factor receptor mutations (n=32), response rate, progression-free survival and overall survival were not superior with EB.

Platinum-based combination chemotherapy remains the standard of care in first-line treatment of unselected NS-NSCLC. Molecular targeted approaches strongly mandate appropriate testing and patient selection.