title: Individual-level data on the relationships of progression-free survival and post-progression survival with overall survival in patients with advanced non-squamous non-small cell lung cancer patients who received second-line chemotherapy.
abstract: The effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). Given the lack of research in this area, we here examined whether progression-free survival (PFS) or post-progression survival (PPS) could serve as valid surrogate endpoints for OS after second-line chemotherapy in advanced NSCLC, using individual-level data. Between April 2009 and June 2011, 39 patients with advanced non-squamous NSCLC who had received second-line chemotherapy following first-line chemotherapy treatment with cisplatin and pemetrexed were analysed. The relationships of PFS and PPS with OS were analysed at the individual level. Spearman rank correlation analyses and linear regression analyses showed that PPS was strongly associated with OS (r = 0.90, p < 0.05, R (2) = 0.85), whereas PFS only moderately correlated with OS (r = 0.76, p < 0.05, R (2) = 0.50). Best response at third-line treatment and number of regimens employed after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). Analysis of individual-level data of patients treated with second-line chemotherapy suggested that PPS may be used as a surrogate for OS in patients with advanced non-squamous NSCLC with unknown oncogenic driver mutations and therefore limited options for subsequent chemotherapy. Moreover, our findings suggest that subsequent treatment after disease progression following second-line chemotherapy may greatly influence OS. However, these results should be validated in further large-scale studies.
authors: Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-chou, Suntou-gun, Shizuoka, 411-8777, Japan, hi.imai@scchr.jp.
authors: Hisao
authors: H
authors: Imai
authors: Keita
authors: K
authors: Mori
authors: Akira
authors: A
authors: Ono
authors: Hiroaki
authors: H
authors: Akamatsu
authors: Tetsuhiko
authors: T
authors: Taira
authors: Hirotsugu
authors: H
authors: Kenmotsu
authors: Tateaki
authors: T
authors: Naito
authors: Kyoichi
authors: K
authors: Kaira
authors: Haruyasu
authors: H
authors: Murakami
authors: Masahiro
authors: M
authors: Endo
authors: Takashi
authors: T
authors: Nakajima
authors: Toshiaki
authors: T
authors: Takahashi
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy / Q000473:pathology; D000068437:Pemetrexed; D016896:Treatment Outcome
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin