Primo N Lara1, James Moon2, Mary W Redman2, Thomas J Semrad3, Karen Kelly3, Jeffrey Allen4, Barbara Gitlitz5, Philip C Mack3, David R Gandara3. 1. University of California Davis Comprehensive Cancer Center, Sacramento, CA. Electronic address: primo.lara@ucdmc.ucdavis.edu. 2. SWOG Statistical Center and the Fred Hutchinson Cancer Research Center, Seattle, WA. 3. University of California Davis Comprehensive Cancer Center, Sacramento, CA. 4. University of California Davis Comprehensive Cancer Center, Sacramento, CA; Humboldt Medical Specialists, Eureka, CA. 5. University of Southern California, Los Angeles, CA.
Abstract
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.
RCT Entities:
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-SCLCpatients 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-SCLCpatients, 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.
Authors: Primo N Lara; Kari Chansky; Angela M Davies; Wilbur A Franklin; Paul H Gumerlock; Perry P Guaglianone; James N Atkins; Nichole Farneth; Philip C Mack; John J Crowley; David R Gandara Journal: J Thorac Oncol Date: 2006-11 Impact factor: 15.609
Authors: Barbara J Gitlitz; James Moon; Bonnie S Glisson; H Joachim Reimers; Martin J Bury; Justin D Floyd; Thomas K Schulz; P Kothai Sundaram; Christopher Ho; David R Gandara Journal: J Thorac Oncol Date: 2010-11 Impact factor: 15.609
Authors: Nathan R Foster; Yingwei Qi; Qian Shi; James E Krook; John W Kugler; James R Jett; Julian R Molina; Steven E Schild; Alex A Adjei; Sumithra J Mandrekar Journal: Cancer Date: 2010-10-19 Impact factor: 6.860
Authors: Primo N Lara; James Moon; Mary W Redman; Thomas J Semrad; Karen Kelly; Jeffrey W Allen; Barbara J Gitlitz; Philip C Mack; David R Gandara Journal: J Thorac Oncol Date: 2015-01 Impact factor: 15.609
Authors: Primo N Lara; Mary W Redman; Karen Kelly; Martin J Edelman; Stephen K Williamson; John J Crowley; David R Gandara Journal: J Clin Oncol Date: 2008-01-20 Impact factor: 44.544
Authors: Jeffrey W Allen; James Moon; Mary Redman; Shirish M Gadgeel; Karen Kelly; Philip C Mack; Hanna M Saba; Mohamed K Mohamed; Mohammad Jahanzeb; David R Gandara Journal: J Clin Oncol Date: 2014-07-07 Impact factor: 44.544