Six-Month Progression-Free Survival as the Primary Endpoint to Evaluate the Activity of New Agents as Second-line Therapy for Advanced Urothelial Carcinoma |
| |
| Affiliation: | 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;1. McMaster University, Ontario, Canada;2. University Hospital del Mar-IMIM, Barcelona, Spain;3. Institut de Recherche Pierre Fabre, Boulogne, France;4. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA;5. Heinrich Heine University, Dusseldorf, Germany;6. University Federico II, Naples, Italy;7. Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY;8. University of Utah, Salt Lake City, UT;9. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy;10. University of Alabama, Birmingham Comprehensive Cancer Center, Birmingham, AL;1. Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas;2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;1. Department of Gastroenterology, Navarra Hospitalary Complex, Pamplona, Spain;2. Department of Gastroenterology, Araba University Hospital, Vitoria, Spain;1. Department of Medical Oncology, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy;2. Cancer Sciences Unit, University of Southampton, Southampton, UK;3. Dipartimento di Scienze Cliniche Specialistiche ed Odontostomatologiche, Clinica di Urologia, AOU Ospedali Riuniti, Università Politecnica delle Marche, Ancona, Italy;4. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy;5. NIHR Wellcome Trust Clinical Research Facility, University of Southampton, Southampton, UK |
| |
| Abstract: | ObjectiveSecond-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.MethodsTen 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.ResultsIn 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%, 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 (R2 = 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.ConclusionsPFS6 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 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
