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

Abstract：

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 (R(2) = 0.55, Pearson correlation = 0.66) and individual levels (82%, Қ = 0.45). Response correlated with OS12 at the individual level less robustly (78%, Қ = 0.36), and the trial level association was not statistically significant (R(2) = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%, Қ = 0.44) appeared stronger than the correlation of response (76%, Қ = 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.

journal_name

Clin Genitourin Cancer

journal_title

Clinical genitourinary cancer

authors

Agarwal N,Bellmunt J,Maughan BL,Boucher KM,Choueiri TK,Qu AQ,Vogelzang NJ,Fougeray R,Niegisch G,Albers P,Wong YN,Ko YJ,Sridhar SS,Tantravahi SK,Galsky MD,Petrylak DP,Vaishampayan UN,Mehta AN,Beer TM,Sternberg CN,R

doi

10.1016/j.clgc.2013.09.002

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

130-7

issue

eissn

1558-7673

issn

1938-0682

pii

S1558-7673(13)00213-9

journal_volume

pub_type

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