Relationship between Response and Survival in More Than 50,000 Patients with Advanced Non-small Cell Lung Cancer Treated with Systemic Chemotherapy in 143 Phase III Trials

BackgroundThe association between the objective response to chemotherapy and survival has not yet been fully evaluated using large cohorts in advanced non-small cell lung cancer.MethodsWe searched for phase III trials conducted between 1991 and 2006 to investigate the role of systemic chemotherapy for advanced non-small cell lung cancer. Associations were tested by multiple regression analysis.ResultsOf the 1255 trials screened, 143 met our criteria, involving 50,569 patients with 309 chemotherapy regimens. In the first-line setting, the median intention-to-treat objective response rate (ORR) and disease control rate (DCR) were 26.4% and 62.5%, respectively (43,551 randomized patients; 290 trials). The median of the median survival time (MST) was 8.5 months in the first-line setting, and both the ORR and DCR were significantly associated with the MST in the multivariate analysis (regression coefficient = 0.0788 [p < 0.0001] and 0.0794 [p < 0.0001], respectively). Subgroup analysis showed no correlation between the ORR and MST in patients receiving chemotherapy containing molecular-targeted agents (p = 0.3817). In the second-line or later setting, the median ORR was only 6.8%, whereas the median DCR was 42.4% (4318 randomized patients; 19 trials). The median MST (6.6 months) was not associated with the ORR (p = 0.6992), but was associated with the DCR (p = 0.0129), despite the small sample size.ConclusionsWe found that survival was associated with both the ORR and DCR in the first-line setting, although it should be interpreted cautiously because of the abstracted data–based analysis. Regarding chemotherapy regimens containing molecular-targeted agents and salvage chemotherapy regimens, further assessments are warranted to clarify the association between the parameters.