Results A total of 482 patients underwent randomization to vinorelbine plus cisplatin (242 patients) or observation (240); 45 percent of the patients had pathological stage IB disease and 55 percent had stage II, and all had an Eastern Cooperative Oncology Group performance status score of 0 or 1. In both groups, the median age was 61 years, 65 percent were men, and 53 percent had adenocarcinomas. Chemotherapy caused neutropenia in 88 percent of patients (including grade 3 febrile neutropenia in 7 percent) and death from toxic effects in two patients (0.8 percent). Nonhematologic toxic effects of chemotherapy were fatigue (81 percent of patients), nausea (80 percent), anorexia (55 percent), vomiting (48 percent), neuropathy (48 percent), and constipation (47 percent), but severe (grade 3 or greater) toxic effects were uncommon (<10 percent). Overall survival was significantly prolonged in the chemotherapy group as compared with the observation group (94 vs. 73 months; hazard ratio for death, 0.69; P=0.04), as was relapse-free survival (not reached vs. 46.7 months; hazard ratio for recurrence, 0.60; P<0.001). Five-year survival rates were 69 percent and 54 percent, respectively (P=0.03).

Conclusions Adjuvant vinorelbine plus cisplatin has an acceptable level of toxicity and prolongs disease-free and overall survival among patients with completely resected early-stage non–small-cell lung cancer. Subgroup analyses indicate that the survival advantage in our trial was most prominent in patients with stage II disease. We cannot explain why the benefit in patients with stage IB disease was less and did not reach statistical significance (7 percent benefit at five years, vs. 20 percent among those with stage II disease). The number of patients with stage IB disease was small, the number of events was smaller than had been anticipated when the subgroup analysis was planned, and the statistical test for stage-by-treatment interaction was not significant (P=0.13). Therefore, it is important not to place too much emphasis on this subgroup analysis.

A British Medical Research Council meta-analysis of cisplatin-based chemotherapy after surgery for stage I through stage III non–small-cell lung cancer showed a 13 percent reduction in the risk of death and an absolute improvement in survival of 5 percent at five years, but when compared with observation alone after surgery, the difference was statistically insignificant (P=0.08). More recently, a large international trial of adjuvant chemotherapy that used cisplatin plus either a vinca alkaloid or etoposide (International Adjuvant Lung Cancer Trial [IALT]) reported similar results, with a 4.1 percent improvement in five-year survival (hazard ratio, 0.86; P<0.03)
 

The median survival after chemotherapy was significantly prolonged, at 94 months (95 percent confidence interval, 73 to not reached), as compared with 73 months (95 percent confidence interval, 48 to not reached) in the observation group (hazard ratio, 0.69; 95 percent confidence interval, 0.52 to 0.91; P=0.009; P=0.04 after adjustment for interim analyses). There was an absolute survival advantage of 15 percentage points at five years — 69 percent (95 percent confidence interval, 62 to 75 percent) in the vinorelbine–cisplatin group and 54 percent (95 percent confidence interval, 48 to 61 percent) with observation alone (P=0.03).

Subgroup analyses according to stratification factors did not show a statistically significant improvement in overall survival among patients with stage IB non–small-cell lung cancer in the chemotherapy group as compared with the observation group (P=0.79) The median survival among patients with stage II non–small-cell lung cancer was 41 months in the observation group and 80 months in the chemotherapy group (hazard ratio, 0.59; 95 percent confidence interval, 0.42 to 0.85; P=0.004).