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 11 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 100mg/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 100mg/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 100mg/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 A1 and B1 respectively: duration of response,vas similar (8.2 versus 8.4 months): median time to progression was 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 neutropertia 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 firs-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 long-term survivors, despite the absence of efficacy of the second-line in our study.