TY - JOUR
T1 - Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer
T2 - Evidence from a meta-analysis of 2334 patients from 5 randomised trials
AU - Laporte, Silvy
AU - Squifflet, Pierre
AU - Baroux, Noémie
AU - Fossella, Frank
AU - Georgoulias, Vassilis
AU - Pujol, Jean Louis
AU - Douillard, Jean Yves
AU - Kudoh, Shinzohy
AU - Pignon, Jean Pierre
AU - Quinaux, Emmanuel
AU - Buyse, Marc
PY - 2013
Y1 - 2013
N2 - Objectives: To investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Design: Meta-analysis of individual patient data from randomised trials. Setting: Five randomised controlled trials comparing docetaxel-based chemotherapy with vinorelbine-based chemotherapy for the first-line treatment of NSCLC. Participants: 2331 patients with advanced NSCLC. Primary and secondary outcome measures: Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. The surrogate threshold effect was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS. Results: The median follow-up of patients still alive was 23.4 months. Median OS was 10 months and median PFS was 5.5 months. The treatment effects on PFS and OS were correlated, whether using centres (R2=0.62, 95% CI 0.52 to 0.72) or prognostic strata (R2=0.72, 95% CI 0.60 to 0.84) as units of analysis. The surrogate threshold effect was a PFS hazard ratio (HR) of 0.49 using centres or 0.53 using prognostic strata. Conclusions: These analyses provide only modest support for considering PFS as an acceptable surrogate for OS in patients with advanced NSCLC. Only treatments that have a major impact on PFS (risk reduction of at least 50%) would be expected to also have a significant effect on OS. Whether these results also apply to targeted therapies is an open question that requires independent evaluation.
AB - Objectives: To investigate whether progression-free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in advanced non-small-cell lung cancer (NSCLC). Design: Meta-analysis of individual patient data from randomised trials. Setting: Five randomised controlled trials comparing docetaxel-based chemotherapy with vinorelbine-based chemotherapy for the first-line treatment of NSCLC. Participants: 2331 patients with advanced NSCLC. Primary and secondary outcome measures: Surrogacy of PFS for OS was assessed through the association between these endpoints and between the treatment effects on these endpoints. The surrogate threshold effect was the minimum treatment effect on PFS required to predict a non-zero treatment effect on OS. Results: The median follow-up of patients still alive was 23.4 months. Median OS was 10 months and median PFS was 5.5 months. The treatment effects on PFS and OS were correlated, whether using centres (R2=0.62, 95% CI 0.52 to 0.72) or prognostic strata (R2=0.72, 95% CI 0.60 to 0.84) as units of analysis. The surrogate threshold effect was a PFS hazard ratio (HR) of 0.49 using centres or 0.53 using prognostic strata. Conclusions: These analyses provide only modest support for considering PFS as an acceptable surrogate for OS in patients with advanced NSCLC. Only treatments that have a major impact on PFS (risk reduction of at least 50%) would be expected to also have a significant effect on OS. Whether these results also apply to targeted therapies is an open question that requires independent evaluation.
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U2 - 10.1136/bmjopen-2012-001802
DO - 10.1136/bmjopen-2012-001802
M3 - Article
C2 - 23485717
AN - SCOPUS:84877648468
SN - 2044-6055
VL - 3
JO - BMJ open
JF - BMJ open
IS - 3
M1 - e001802
ER -