Potential surrogate endpoints for overall survival in locoregionally advanced nasopharyngeal carcinoma: an analysis of a phase III randomized trial

• Published in: Scientific reports 2015-07, Vol.5 (1), p.12502-12502, Article 12502
• Main Authors: Chen, Yu-Pei, Chen, Yong, Zhang, Wen-Na, Liang, Shao-Bo, Zong, Jing-Feng, Chen, Lei, Mao, Yan-Ping, Tang, Ling-Long, Li, Wen-Fei, Liu, Xu, Guo, Ying, Lin, Ai-Hua, Liu, Meng-Zhong, Sun, Ying, Ma, Jun
• Format: Article
• Language: English
• Subjects: 692/308/2779/777; 692/699/67/1059; Adult; Aged; Biomarkers; Cancer therapies; Carcinoma; Chemoradiotherapy; Chemotherapy; Clinical trials; Clinical Trials, Phase III as Topic; Cohort Studies; Correlation coefficient; Female; Follow-Up Studies; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Male; Middle Aged; multidisciplinary; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms - mortality; Nasopharyngeal Neoplasms - pathology; Neoplasm Staging; Oncology; Prognosis; Radiation therapy; Randomized Controlled Trials as Topic; Science; Survival; Throat cancer; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep12502

The gold standard endpoint in trials of locoregionally advanced nasopharyngeal carcinoma (NPC) is overall survival (OS). Using data from a phase III randomized trial, we evaluated whether progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) or locoregional failure-free survival (LR-FFS) could be reliable surrogate endpoints for OS. Between July 2002 and September 2005, 316 eligible patients with stage III-IVB NPC were randomly assigned to receive either radiotherapy alone or chemoradiotherapy. 2- and 3-year PFS, FFS, D-FFS and LR-FFS were tested as surrogate endpoints for 5-year OS using Prentice’s four criteria. The Spearman’s rank correlation coefficient was calculated to assess the strength of the associations. After a median follow-up time of 5.8 years, 2- and 3-year D-FFS and LR-FFS were not significantly different between treatment arms, in rejection of Prentice’s second criterion. Being consistent with all Prentice’s criteria, 2- and 3-year PFS and FFS were valid surrogate endpoints for 5-year OS; the rank correlation coefficient was highest (0.84) between 3-year PFS and 5-year OS. In conclusion, PFS and FFS at 2 and 3 years may be candidate surrogate endpoints for OS at 5 years; 3-year PFS may be more appropriate for early assessment of long-term survival.