Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma

被引：26

作者：

Agarwal, Neeraj ^{[1
]}

Bellmunt, Joaquim ^{[2
]}

Maughan, Benjamin L. ^{[1
]}

Boucher, Kenneth M. ^{[3
]}

Choueiri, Toni K. ^{[4
,5
]}

Qu, Angela Q. ^{[4
,5
]}

Vogelzang, Nicholas J. ^{[6
]}

Fougeray, Ronan ^{[7
]}

Niegisch, Guenter ^{[8
]}

Albers, Peter ^{[8
]}

Wong, Yu-Ning ^{[9
]}

Ko, Yoo-Joung ^{[10
]}

Sridhar, Srikala S. ^{[11
]}

Tantravahi, Srinivas K. ^{[1
]}

Galsky, Matthew D. ^{[12
]}

Petrylak, Daniel P. ^{[13
]}

Vaishampayan, Ulka N. ^{[14
]}

Mehta, Amitkumar N. ^{[15
]}

Beer, Tomasz M. ^{[16
]}

Sternberg, Cora. N. ^{[17
]}

Rosenberg, Jonathan E. ^{[18
]}

Sonpavde, Guru ^{[15
]}

机构：

[1] Univ Utah, Huntsman Canc Inst, Dept Internal Med Med Oncol, Salt Lake City, UT USA

[2] Univ Hosp del Mar IMIM, Barcelona, Spain

[3] Univ Utah, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA

[4] Dana Farber Canc Inst, Dept Med Solid Tumor Oncol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Boston, MA USA

[6] Comprehens Canc Ctr Nevada, Las Vegas, NV USA

[7] Inst Rech Pierre Fabre, Boulogne, France

[8] Univ Dusseldorf, Dept Urol, Dusseldorf, Germany

[9] Fox Chase Canc Ctr, Dept Med Oncol, Philadelphia, PA 19111 USA

[10] Sunnybrook Odette Canc Ctr, Dept Med, Toronto, ON, Canada

[11] Princess Margaret Hosp, Dept Med, Toronto, ON M4X 1K9, Canada

[12] Mt Sinai Sch Med, Tisch Canc Ctr Inst, Dept Med Hematol & Med Oncol, New York, NY USA

[13] Yale Univ, Ctr Canc, Dept Internal Med Med Oncol, New Haven, CT USA

[14] Wayne State Univ, Dept Oncol, Detroit, MI USA

[15] UAB Comprehens Canc Ctr, Dept Med Hematol Oncol, Birmingham, AL 35294 USA

[16] Oregon Hlth & Sci Univ, Knight Canc Inst, Dept Med Hematol Oncol, Portland, OR 97201 USA

[17] San Camillo & Forlanini Hosp, Dept Med Oncol, Rome, Italy

[18] Mem Sloan Kettering Canc Ctr, Dept Med Hematol Oncol, New York, NY 10021 USA

来源：

CLINICAL GENITOURINARY CANCER | 2014年 / 12卷 / 02期

关键词：

Advanced urothelial carcinoma; Intermediate endpoint; Overall survival; Progression-free survival at 6 months; Second-line treatment; TRANSITIONAL-CELL CARCINOMA; PHASE-III TRIAL; BLADDER-CANCER; PACLITAXEL; CHEMOTHERAPY; GEMCITABINE; VINFLUNINE; CISPLATIN; METHOTREXATE; MULTICENTER;

D O I：

10.1016/j.clgc.2013.09.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study examined the association of progression-free survival at 6 months with overall survival in the context of second-line therapy of advanced urothelial carcinoma in pooled patient-level data from 10 phase II trials and then externally validated in a large phase III trial. Progression-free survival at 6 months was significantly correlated with overall survival and is an innovative primary endpoint to evaluate new agents in this setting. 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%, K = 0.45). Response correlated with OS12 at the individual level less robustly (78%,. = 0.36), and the trial level association was not statistically significant (R-2 = 0.16, Pearson correlation = 0.37). The correlation of PFS6 (81%,K = 0.44) appeared stronger than the correlation of response (76%, K = 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. (C) 2014 Elsevier Inc. All rights reserved.

引用

页码：130 / 137

页数：8

共 21 条

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