251. Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer
- Author
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Akiko Hisamoto-Sato, Yoshiro Fujiwara, Frances A. Shepherd, Paolo Chiodini, Eiki Ichihara, Mitsune Tanimoto, Katsuyuki Kiura, Etsuji Suzuki, Massimo Di Maio, Lothar R. Pilz, Christian Manegold, Masahiro Tabata, Nagio Takigawa, Katsuyuki Hotta, Martin Reck, Hotta, K, Suzuki, E, Di Maio, M, Chiodini, Paolo, Fujiwara, Y, Takigawa, N, Ichihara, E, Reck, M, Manegold, C, Pilz, L, Hisamoto Sato, A, Tabata, M, Tanimoto, M, Shepherd, Fa, and Kiura, K.
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Coefficient of determination ,Phase iii trials ,Disease-Free Survival ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Overall survival ,Carcinoma ,Humans ,Molecular Targeted Therapy ,Progression-free survival ,Lung cancer ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Surrogate endpoint ,business.industry ,medicine.disease ,Surgery ,Clinical trial ,Clinical Trials, Phase III as Topic ,business - Abstract
Background: We examined how crossover therapy might affect the association between progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC). Methods: We extracted PFS- and OS-hazard ratios (HRs) in phase III trials of molecular-targeted agents for advanced NSCLC. Their relationship was modeled in a linear function with the coefficient of determination (R-squared) to assess the correlation between PFS and OS. Results: Thirty-four trials with 35 pairs for the investigational and reference arms were identified (24,158 patients). Overall, there was little correlation between PFS- and OS-HRs (R-squared = 0.14), suggesting PFS-HR could account only for 14% of variation in OS-HR The median proportion of crossover therapy per trial was 20%. If patients seldom crossed over (none or = 1%, however, R-squared declined considerably (>= 1% to = 20% to = 40%, R-squared = 0.27). Conclusions: A PFS advantage seldom is associated with an OS advantage any longer. Our analysis suggests this is due to a high level of crossover now that an increasing number of active agents are available for NSCLC. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
- Published
- 2013