Six-month progression-free survival as the primary endpoint to evaluate the activity of new agents as second-line therapy for advanced urothelial carcinoma

Neeraj Agarwal, Joaquim Bellmunt, Benjamin L. Maughan, Kenneth M. Boucher, Toni K. Choueiri, Angela Q. Qu, Nicholas J. Vogelzang, Ronan Fougeray, Guenter Niegisch, Peter Albers, Yu Ning Wong, Yoo Joung Ko, Srikala S. Sridhar, Srinivas K. Tantravahi, Matthew D. Galsky, Daniel P. Petrylak, Ulka N. Vaishampayan, Amitkumar N. Mehta, Tomasz M. Beer, Cora N. SternbergJonathan E. Rosenberg, Guru Sonpavde

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Objective Second-line systemic therapy for advanced urothelial carcinoma (UC) has substantial unmet needs, and current agents show dismal activity. Second-line trials of metastatic UC have used response rate (RR) and median progression-free survival (PFS) as primary endpoints, which may not reflect durable benefits. A more robust endpoint to identify signals of durable benefits when investigating new agents in second-line trials may expedite drug development. PFS at 6 months (PFS6) is a candidate endpoint, which may correlate with overall survival (OS) at 12 months (OS12) and may be applicable across cytostatic and cytotoxic agents. Methods Ten second-line phase II trials with individual patient outcomes data evaluating chemotherapy or biologics were combined for discovery, followed by external validation in a phase III trial. The relationship between PFS6/RR and OS12 was assessed at the trial level using Pearson correlation and weighted linear regression, and at the individual level using Pearson chi-square test with Yates continuity correction. Results In the discovery dataset, a significant correlation was observed between PFS6 and OS12 at the trial (R2 = 0.55, Pearson correlation = 0.66) and individual levels (82%, Òš = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Òš = 0.36), and the trial level association was not statistically significant (R2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Òš = 0.44) appeared stronger than the correlation of response (76%, Òš = 0.17) with OS12 in the external validation dataset. Conclusions PFS6 is strongly associated with OS12 and appears more optimal than RR to identify active second-line agents for advanced UC.

Original languageEnglish (US)
Pages (from-to)130-137
Number of pages8
JournalClinical Genitourinary Cancer
Issue number2
StatePublished - Apr 2014


  • Advanced urothelial carcinoma
  • Intermediate endpoint
  • Overall survival
  • Progression-free survival at 6 months
  • Second-line treatment

ASJC Scopus subject areas

  • Oncology
  • Urology


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