Lung Cancer. 2012 Nov 16. pii: S0169-5002(12)00582-X. doi: 10.1016/j.lungcan.2012.10.007. [Epub ahead of print]
Progression-free survival and overall survival in phase III trials of molecular-targeted agents in advanced non-small-cell lung cancer.
Hotta K, Suzuki E, Di Maio M, Chiodini P, Fujiwara Y, Takigawa N, Ichihara E, Reck M, Manegold C, Pilz L, Hisamoto-Sato A, Tabata M, Tanimoto M, Shepherd FA, Kiura K.
Source
Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan. Electronic address: khotta@md.okayama-u.ac.jp.
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%), the association between PFS- and OS-HRs was strong (R-squared=0.69). When the proportion of crossover was ≥1%, however, R-squared declined considerably (≥1% to <20% crossover, R-squared=0.27; ≥20% to <40%, R-squared=0.06; and ≥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.
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