Disease Control Rate at 8 Weeks Predicts Subsequent Survival in Platinum-Treated Extensive Stage Small-Cell Lung Cancer: Results From the Southwest Oncology Group (SWOG) Database

作者：Lara Primo N Jr^*; Moon James; Redman Mary W; Semrad Thomas J; Kelly Karen; Allen Jeffrey; Gitlitz Barbara; Mack Philip C; Gandara David R

来源：Clinical Lung Cancer, 2016, 17(2): 113-118.

DOI：10.1016/j.cllc.2015.09.003

• Clinical trials
• Disease control rate
• Landmark analysis
• Outcomes
• Small-cell lung cancer
• Targeted therapy
• Tumor assessment

In phase 2 trials of investigational agents in relapsed/refractory small-cell lung cancer (SCLC), response rate is often used as an efficacy measure. In this Southwest Oncology Group (SWOG) database of SCLC patients enrolled onto phase 2 trials of targeted therapies, disease control rate at 8 weeks was a better predictor of subsequent survival than tumor response.
Background: Overall response rate is frequently used as an end point in phase 2 trials of platinum-treated extensive stage (ES) small-cell lung cancer (SCLC). We hypothesized that disease control rate (DCR) would be a superior surrogate for subsequent survival outcomes. Methods: Updated patient-level data from Southwest Oncology Group (SWOG) trials in second- and/or third-line ES-SCLC patients were pooled. Landmark analysis was performed among patients alive at 8 weeks for overall survival (OS) measured from the 8-week landmark. Association of clinical prognostic factors with DCR was assessed using logistic regression. A Cox proportional hazard model was used to assess the associations between DCR at the landmark time and subsequent OS, adjusted for prognostic factors. Results: Of the 319 ES-SCLC patients, 263 were alive at the 8-week landmark and constituted the pooled study population. Only 8 patients had a response. Disease control at 8 weeks was seen in 98 patients. Bivariate analysis of OS from the 8-week landmark revealed that DCR (hazard ratio [HR], 0.47; P < .0001) and elevated lactate dehydrogenase (HR, 1.70; P = .0004) were significantly associated with OS. In multivariable analysis, DCR remained an independent predictor of subsequent survival from the 8 week landmark (HR, 0.50; P < .0001). Conclusion: In this large second- and third-line ES-SCLC database, DCR at 8 weeks was found to be a significant predictor of subsequent survival in patients receiving investigational therapy. These results have critical implications in the selection of surrogate end points in future prospective ES-SCLC trials.

• 出版日期2016-3