role of survival post-progression in phase iii trials of systemic chemotherapy in advanced non-small-cell lung cancer a systematic review角色的生存post-progression iii期试验中系统性化疗在晚期非小细胞肺癌的系统评价.pdfVIP

Role of Survival Post-Progression in Phase III Trials of Systemic Chemotherapy in Advanced Non-Small-Cell Lung Cancer: A Systematic Review Katsuyuki Hotta*, Katsuyuki Kiura, Yoshiro Fujiwara, Nagio Takigawa, Akiko Hisamoto, Eiki Ichihara, Masahiro Tabata, Mitsune Tanimoto Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan Abstract Background: In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS). Methods and Findings: Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r2) to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p,0.001) in parallel to the increase in MST (11.253-day increase per year; p,0.001); MPFS improved little (1.863- day increase per year). Overall, a stronger association was observed between MST and SPP (r2 = 0.8917) than MST and MPFS time (r2 = 0.2563), suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r2 = 0.4428, 0.7242, and 0.9081 in 1988–1994, 1995–2001, a