Sequential two-line strategy for stage IV non-small-cell lung cancer: docetaxel–cisplatin versus vinorelbine–cisplatin followed by cross-over to single-agent docetaxel or vinorelbine at progression: final results of a randomised phase II study

Background: This phase II trial compared docetaxel-cisplatin (DC) with vinorelbine-cisplatin (VC), both as first-line therapy followed by cross-over at progression to single-agent vinorelbine or docetaxel in advanced non-small-cell lung cancer (NSCLC). Methods: Overall, 115 patients received DC (docetaxel 75 mg/m 2 and cisplatin 100 mg/m 2 both on day 1, every 3 weeks, arm A1) and 118 VC (vinorelbine 30 mg/m 2 /week on days 1 and 8 and cisplatin 100 mg/m 2 on day 1, every 3 weeks, arm B1) for six cycles, and subsequently maintained by monotherapy with docetaxel (A1) or vinorelbine (B1) with cross-over on disease progression to vinorelbine 30 mg/m 2 days 1 and 8 (A2), or docetaxel 100 mg/m 2 , day 1, both every 3 weeks (B2). The primary end point was overall response rate (ORR). Results: Patient characteristics were balanced; median follow-up was 8.8 months. First-line response rate was 33.9% with DC and 26.3% with VC (P=0.20). In arms Al and B1, respectively: duration of response was similar (8.2 versus 8.4 months); median time to progression was 5 months in both; median survival was 8 versus 9 months (P=0.38); 1-, 2- and 3-year survival was 36% versus 35%, 17% versus 10% and 13% versus 6% (P not significant). However, with a low number of long-term survivors, statistical significance was not reached. Overall, almost half of the patients crossed over to second-line therapy; there were no response with vinorelbine and 6 (11.2%) partial responses with docetaxel. Considering the safety profile, the occurrence of febrile neutropenia was 9.6% with DC and 26.3% with VC. Treatment-related mortality was 2.5% with DC and 8.5% with VC. Conclusions: The trend in favour of the DC arm in ORR, even though statistical significance was not reached, is consistent with previous reports. This study suggests an activity of first-line DC in advanced NSCLC, and that second-line vinorelbine does not provide additional clinical benefit. As already shown in other studies, the use of DC in first-line should provide a better percentage of lone-term survivors, despite the absence of efficacy of the second-line in our study.