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.

Effect of age on the efficacy of adjuvant chemotherapy for resected non–small cell lung cancer

“…30 These recommendations are based on multiple phase 3 trials that compared cisplatin-based doublets with observation after surgical resection. 11,12,31 A large meta-analysis of these trials, the LACE meta-analysis, 15 13 treatment was limited to patients with resected stage IB disease only. Although the combination of carboplatin and paclitaxel was associated with a 17% decrease in the risk of death, this finding did not reach statistical significance (HR, 0.83; 95% CI, 0.64-1.08 [P 5.12]).…”

Tratamento adjuvante em câncer de pulmão de células não pequenas

“…(12,13) Unlike the study conducted by Arriagada et al, (11) those two other studies produced promising results: an improvement in survival was confirmed after a long follow-up period. In another study, (14) this improvement was 11% after more than nine years of follow-up, which is in disagreement with the findings of the Arriagada et al study. (11) In addition, in a recent meta-analysis, (15) extremely positive results were obtained with the cisplatinvinorelbine combination, with a reduction in the overall mortality rate of 8.9% in comparison with observation (hazard ratio [HR] = 0.80; 95% CI: 0.70-0.91; p < 0.001).…”

Post-operative Treatment with Cisplatin and Vinorelbine in Chinese Patients with Non-small Cell Lung Cancer: A Clinical Prospective Analysis of 451 Patients

“…The positive advantage reported in our study also related to higher chemotherapy compliance and more stringent inclusion criteria. The majority of patients received at least 4 cycles of the NP regimen and had a median number of 4.8 cycles (range 1 to 8.4), which was greater than in the previous trials (Arriagada et al, 2004;Butts et al, 2010). In addition, the positive outcome may stem from a restrict criteria for enrolling patients.…”

“…The CALGB 9633 trial results in a similar finding (Strauss et al, 2008). Furthermore, the ANITA (Adjuvant Navelbine International Trialist Association) and JBR-10 (National Cancer Institute of Canada Clinical Trial Group) trials also confirm the survival benefit of adjuvant cisplatinvinorelbine chemotherapy in patients with NSCLC at I-IIIA even after follow-up for 9.3 years (Winton et al, 2005;Douillard et al, 2006;Butts et al, 2010). In addition, the LACE (Lung Adjuvant Cisplatin Evaluation) collaborative group and ISA (Italian Survey on adjuvant treatment trial) independently confirm that the effect of NP treatment was significantly better than that of platinumbased combination Douillard et al, 2010;Banna et al, 2011).…”