Randomized Phase III Study of Gemcitabine and Vinorelbine Versus Gemcitabine, Vinorelbine, and Cisplatin in the Treatment of Advanced Non-Small-Cell Lung Cancer: From the German and Swiss Lung Cancer Study Group

Purpose To evaluate whether cisplatin-based chemotherapy (gemcitabine, vinorelbine, and cisplatin [GVP]) prolongs overall survival in comparison to cisplatin-free chemotherapy (gemcitabine and vinorelbine [GV]) as first-line treatment in patients with advanced non-small-cell lung cancer (NSCLC). Patients and Methods Between September 1999 and June 2001, 300 patients with NSCLC stage IIIB with malignant pleural effusion or stage IV disease were randomly assigned to receive GV (gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks) or GVP (gemcitabine 1000 mg/m2 + vinorelbine 25 mg/m2 on days 1 and 8 + cisplatin 75 mg/m2 on day 2 every 3 weeks). Primary end point of the study was overall survival. Results Two hundred eighty-seven patients (GV, 143 patients; GVP, 144 patients) were eligible for analysis. At the time of analysis, April 15, 2002, 209 patients (GV, 103 patients; GVP, 106 patients) of 287 patients had died (73%). No statistically significant difference was observed for overall survival (P = .73; median survival, 35.9 versus 32.4 weeks; 1-year survival rate, 33.6% versus 27.5%) as well as for event-free survival (P = .35; median time-to-event, 19.3 versus 22.3 weeks) between GV and GVP. Two hundred fourteen patients were assessable for best response. The overall response rates were 13.0% for GV versus 28.3% for GVP (P = .004; complete responders, 0% versus 3.8%; partial responders, 13.0% versus 24.5%). Hematologic and nonhematologic toxicity was significantly lower in the GV treatment arm compared with GVP. No statistically significant difference in quality of life was observed. Conclusion In this phase III study, the cisplatin-based GVP regimen showed no survival benefit as first-line chemotherapy in advanced NSCLC when compared with the cisplatin-free GV regimen, which was substantially better tolerated.