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Clin Genitourin Cancer. 2014 Apr;12(2):130-7. doi: 10.1016/j.clgc.2013.09.002. Epub 2013 Sep 28.

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

Author information

1
Department of Internal Medicine/Medical Oncology, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
2
University Hospital del Mar-IMIM, Barcelona, Spain.
3
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT.
4
Department of Medicine/Solid Tumor Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.
5
Comprehensive Cancer Centers of Nevada, Las Vegas, NV.
6
Institut de Recherche Pierre Fabre, Boulogne, France.
7
Department of Urology, Heinrich Heine University, Dusseldorf, Germany.
8
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
9
Department of Medicine, Sunnybrook Odette Cancer Centre, Toronto, ON, Canada.
10
Department of Medicine, Princess Margaret Hospital, Toronto, ON, Canada.
11
Department of Medicine/Hematology and Medical Oncology, Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY.
12
Department of Internal Medicine/Medical Oncology, Yale University Cancer Center, New Haven, CT.
13
Department of Oncology, Wayne State University, Detroit, MI.
14
Department of Medicine/Hematology-Oncology, UAB Comprehensive Cancer Center, Birmingham, AL.
15
Department of Medicine/Hematology-Oncology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR.
16
Department of Medical Oncology, San Camillo and Forlanini Hospitals, Rome, Italy.
17
Department of Medicine/Hematology-Oncology, Memorial Sloan Kettering Cancer Center, New York, NY.
18
Department of Medicine/Hematology-Oncology, UAB Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu.

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.

KEYWORDS:

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

PMID:
24220220
PMCID:
PMC4142680
DOI:
10.1016/j.clgc.2013.09.002
[Indexed for MEDLINE]
Free PMC Article

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