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.
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).


CONCLUSIONS
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.
University of California Davis Comprehensive Cancer Center, Sacramento, CA. Electronic address: primo.lara@ucdmc.ucdavis.edu.
Primo N
PN
Lara
SWOG Statistical Center and the Fred Hutchinson Cancer Research Center, Seattle, WA.
James
J
Moon
SWOG Statistical Center and the Fred Hutchinson Cancer Research Center, Seattle, WA.
Mary W
MW
Redman
University of California Davis Comprehensive Cancer Center, Sacramento, CA.
Thomas J
TJ
Semrad
University of California Davis Comprehensive Cancer Center, Sacramento, CA.
Karen
K
Kelly
University of California Davis Comprehensive Cancer Center, Sacramento, CA; Humboldt Medical Specialists, Eureka, CA.
Jeffrey
J
Allen
University of Southern California, Los Angeles, CA.
Barbara
B
Gitlitz
University of California Davis Comprehensive Cancer Center, Sacramento, CA.
Philip C
PC
Mack
University of California Davis Comprehensive Cancer Center, Sacramento, CA.
David R
DR
Gandara
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D017671:Platinum Compounds; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D019772:Topotecan; D007770:L-Lactate Dehydrogenase; D040262:Receptors, Vascular Endothelial Growth Factor
Clinical trials; Disease control rate; Landmark analysis; Outcomes; Small-cell lung cancer; Targeted therapy; Tumor assessment