Guru Sonpavde1, Gregory R Pond2, Jonathan E Rosenberg3, Dean F Bajorin3, Ashley M Regazzi3, Toni K Choueiri4, Angela Q Qu4, Guenter Niegisch5, Peter Albers5, Andrea Necchi6, Giuseppe Di Lorenzo7, Ronan Fougeray8, Robert Dreicer9, Yu-Hui Chen4, Yu-Ning Wong10, Srikala S Sridhar11, Yoo-Joung Ko12, Matthew I Milowsky13, Matthew D Galsky14, Joaquim Bellmunt15. 1. UAB Comprehensive Cancer Center, Birmingham, AL. Electronic address: gsonpavde@uabmc.edu. 2. McMaster University, Ontario, Canada. 3. Memorial Sloan Kettering Cancer Center, New York, NY. 4. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. 5. Heinrich Heine University, Dusseldorf, Germany. 6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. University Federico II, Naples, Italy. 8. Institut de Recherche Pierre Fabre, Boulogne, France. 9. Cleveland Clinic, Cleveland, OH. 10. Fox Chase Cancer Center, Philadelphia, PA. 11. Princess Margaret Hospital, Toronto, ON, Canada. 12. Sunnybrook Odette Cancer Centre, Toronto, ON, Canada. 13. University of North Carolina, Chapel Hill, NC. 14. Tisch Cancer Center Institute, Mount Sinai School of Medicine, New York, NY. 15. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; University Hospital del Mar-IMIM, Barcelona, Spain.
Abstract
BACKGROUND: The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear, and its value as an intermediate end point and association with survival are unknown. MATERIALS AND METHODS: Data from phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy, hemoglobin, performance status, and liver metastasis status were collected. Cox proportional hazards regression was used to evaluate the association of CR and other prognostic factors with outcomes. RESULTS: A total of 789 of 818 patients enrolled in 12 phase II trials had evaluable data. CR and partial response were seen in 14 (1.8%) and 109 (13.8%) patients. Median (95% confidence interval) OS for those with a CR was 21.5 (14.2-34.3) months, compared with 6.7 (6.0-7.0) months in those without a CR (P < .001). Median (95% confidence interval) PFS for those with a CR was 15.7 (8.2-27.1) months, compared with 2.6 (2.4-2.8) months for those without a CR (P < .001). Prior cisplatin and time from prior chemotherapy of ≥ 3 months were associated with CR (P < .05). The presence of poor prognostic factors and suboptimal response to prior therapy did not preclude CR. CONCLUSION: CR occurs in 1.8% of patients receiving salvage therapy for advanced UC and is strongly associated with durable OS and PFS. CR warrants validation as an intermediate end point and may help select agents for further investigation and tumors for molecular interrogation.
BACKGROUND: The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear, and its value as an intermediate end point and association with survival are unknown. MATERIALS AND METHODS: Data from phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy, hemoglobin, performance status, and liver metastasis status were collected. Cox proportional hazards regression was used to evaluate the association of CR and other prognostic factors with outcomes. RESULTS: A total of 789 of 818 patients enrolled in 12 phase II trials had evaluable data. CR and partial response were seen in 14 (1.8%) and 109 (13.8%) patients. Median (95% confidence interval) OS for those with a CR was 21.5 (14.2-34.3) months, compared with 6.7 (6.0-7.0) months in those without a CR (P < .001). Median (95% confidence interval) PFS for those with a CR was 15.7 (8.2-27.1) months, compared with 2.6 (2.4-2.8) months for those without a CR (P < .001). Prior cisplatin and time from prior chemotherapy of ≥ 3 months were associated with CR (P < .05). The presence of poor prognostic factors and suboptimal response to prior therapy did not preclude CR. CONCLUSION:CR occurs in 1.8% of patients receiving salvage therapy for advanced UC and is strongly associated with durable OS and PFS. CR warrants validation as an intermediate end point and may help select agents for further investigation and tumors for molecular interrogation.
Authors: Patrizia Pinciroli; Helen Won; Gopa Iyer; Silvana Canevari; Maurizio Colecchia; Patrizia Giannatempo; Daniele Raggi; Marco A Pierotti; Filippo G De Braud; David B Solit; Jonathan E Rosenberg; Michael F Berger; Andrea Necchi Journal: Clin Genitourin Cancer Date: 2015-08-07 Impact factor: 2.872