title: Individual-level data on the relationships of progression-free survival, post-progression survival, and tumor response with overall survival in patients with advanced non-squamous non-small cell lung cancer.
abstract: The effects of first-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies in patients with non-small cell lung cancer (NSCLC). We examined whether progression-free survival (PFS), post-progression survival (PPS), or tumor response could be valid surrogate endpoints for OS after first-line chemotherapies in advanced NSCLC by using individual-level data, given the lack of research in this area. Between April 2009 and June 2011, 50 patients with advanced non-squamous NSCLC treated with cisplatin and pemetrexed as first-line chemotherapy were analyzed. The relationships of PFS, PPS, and tumor response with OS were analyzed at the individual level. Spearman rank correlation analysis and linear regression analysis showed that PPS was strongly correlated with OS (r = 0.89, P < 0.05, R2 = 0.79), PFS was moderately correlated with OS (r = 0.67, P < 0.05, R2 = 0.39), and tumor shrinkage was weakly correlated with OS (r = 0.36, P < 0.05, R2 = 0.14). Performance status at the beginning of second-line treatment, the best response to second-line treatment, and number of regimens used after progression following first-line chemotherapy were significantly associated with PPS (P < 0.05). Analysis of individual-level data suggested that PPS could 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. Our findings also suggest that subsequent treatment after disease progression following first-line chemotherapy may greatly influence OS. These results should be validated in other larger populations.
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Ono
authors.forename: H
authors.initials: H
authors.lastname: Akamatsu
authors.forename: T
authors.initials: T
authors.lastname: Shukuya
authors.forename: T
authors.initials: T
authors.lastname: Taira
authors.forename: H
authors.initials: H
authors.lastname: Kenmotsu
authors.forename: T
authors.initials: T
authors.lastname: Naito
authors.forename: H
authors.initials: H
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D002945:Cisplatin
keywords: non-small cell lung cancer, overall survival, post-progression survival, progression-free survival, tumor response