Progression-free survival, post-progression survival, and tumor response as surrogate markers for overall survival in patients with extensive small cell lung cancer
Hisao Imai1, Keita Mori2, Kazushige Wakuda1, Akira Ono1, Hiroaki Akamatsu1, Takehito Shukuya1, Tetsuhiko Taira1, Hirotsugu Kenmotsu1, Tateaki Naito1, Kyoichi Kaira1, Haruyasu Murakami1, Masahiro Endo3, Takashi Nakajima4, Nobuyuki Yamamoto5, Toshiaki Takahashi1
1 Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan
2 Clinical Trial Coordination Office, Shizuoka Cancer Center, Shizuoka, Japan
3 Division of Diagnostic Radiology, Shizuoka Cancer Center, Shizuoka, Japan
4 Division of Diagnostic Pathology, Shizuoka Cancer Center, Shizuoka, Japan
5 Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka; Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
Division of Thoracic Oncology, Shizuoka Cancer Center, Nagaizumi-chou, Suntou-gun, Shizuoka 411-8777
Source of Support: None, Conflict of Interest: None
Objectives: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with small cell lung cancer (SCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), and tumor response could be valid surrogate endpoints for OS after first-line chemotherapies for patients with extensive SCLC using individual-level data.
Methods: Between September 2002 and November 2012, we analyzed 49 cases of patients with extensive SCLC who were treated with cisplatin and irinotecan as first-line chemotherapy. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level.
Results: Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.97, p < 0.05, R 2 = 0.94), PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.24), and tumor shrinkage was weakly correlated with OS (r = 0.37, p < 0.05, R 2 = 0.13). The best response to second-line treatment, and the number of regimens employed after progression beyond first-line chemotherapy were both significantly associated with PPS ( p ≤ 0.05).
Conclusion: PPS is a potential surrogate for OS in patients with extensive SCLC. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS.