Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10

Abstract

PURPOSE Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non-small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data. PATIENTS AND METHODS Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis. Results Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms. CONCLUSION Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm.

Fig 1.

CONSORT diagram. Distribution of all patients.

Fig 2.

Overall survival comparisons by treatment arm: (A) for all randomly assigned patients; (B) for patients with stage II disease; (C) for patients with stage IB (T2N0) disease. HR, hazard ratio.

Fig 3.

(A) Survival comparison for stage IB patients with primary tumor less than 4 cm by treatment arm. (B) Survival comparison for stage IB patients with primary tumor 4 cm or greater by treatment arm. Interaction, P = .022. HR, hazard ratio.

Fig 4.

Cumulative incidence plots for death due to non–small-cell lung cancer or other causes by treatment arm.

Fig A1.

Overall survival RAS wild type versus mutant. (A) Wild type; (B) mutant – RAS positive. Interaction, P = .9725. HR, hazard ratio.

Fig A2.

Disease-specific survival RAS wild type versus mutant. (A) Wild type; (B) mutant – RAS positive. Interaction, P = .202. HR, hazard ratio.