Risa L Wong1,2, Lorin A Ferris1, Olivia A Do1, Sarah K Holt3, Jorge D Ramos1,2, Simon J Crabb4, Cora N Sternberg5, Joaquim Bellmunt6, Sylvain Ladoire7, Ugo De Giorgi8, Lauren C Harshman9, Ulka N Vaishampayan10, Andrea Necchi11, Sandy Srinivas12, Sumanta K Pal13, Guenter Niegisch14, Tanya B Dorff15, Matthew D Galsky16, Evan Y Yu1,2. 1. Department of Medicine, University of Washington, Seattle, Washington, USA. 2. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. 3. Department of Urology, University of Washington, Seattle, Washington, USA. 4. Cancer Sciences Unit, University of Southampton, Southampton, United Kingdom. 5. Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York, USA. 6. Hospital Del Mar, Barcelona, Spain. 7. Georges-François Leclerc Cancer Center, Dijon, France. 8. Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori IRCCS, Meldola, Italy. 9. Dana-Farber Cancer Institute, Boston, Massachusetts, USA. 10. Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, USA. 11. Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy. 12. Stanford University, Palo Alto, California, USA. 13. City of Hope Comprehensive Cancer Center, Duarte, California, USA. 14. Department of Urology, Medical Faculty, Heinrich-Heine-University, Germany. 15. University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA. 16. Mount Sinai Medical Center, New York, New York, USA.
Abstract
BACKGROUND: Fit patients with metastatic urothelial carcinoma (mUC) receive first-line platinum-based combination chemotherapy (fPBC) as standard of care and may receive additional later-line chemotherapy after progression. Our study compares outcomes with subsequent platinum-based chemotherapy (sPBC) versus subsequent non-platinum-based chemotherapy (sNPBC). MATERIALS AND METHODS: Patients from 27 international centers in the Retrospective International Study of Cancers of the Urothelium (RISC) who received fPBC for mUC and at least two cycles of subsequent chemotherapy were included in this study. A multivariable Cox proportional hazards model compared overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred thirty-five patients received sPBC and 161 received sNPBC. Baseline characteristics were similar between groups, except patients who received sPBC had higher baseline hemoglobin, higher disease control rate with fPBC, and longer time since fPBC. OS was superior in the sPBC group (median 7.9 vs 5.5 months) in a model adjusting for comorbidity burden, performance status, liver metastases, number of fPBC cycles received, best response to fPBC, and time since fPBC (hazard ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .035). There was no difference in PFS. More patients in the sPBC group achieved disease control than in the sNPBC group (57.4% vs 44.8%; p = .041). Factors associated with achieving disease control in the sPBC group but not the sNPBC group included longer time since fPBC, achieving disease control with fPBC, and absence of liver metastases. CONCLUSION: After receiving fPBC for mUC, patients who received sPBC had better OS and disease control. This may help inform the choice of subsequent chemotherapy in patients with mUC. IMPLICATIONS FOR PRACTICE: Patients with progressive metastatic urothelial carcinoma after first-line platinum-based combination chemotherapy may now receive immuno-oncology agents, erdafitinib, enfortumab vedotin, or sacituzumab govitecan-hziy; however, those ineligible for these later-line therapies or who progress after receiving them may be considered for subsequent chemotherapy. In this retrospective study of 296 patients, survival outcomes and disease control rates were better in those receiving subsequent platinum-based rechallenge compared with non-platinum-based chemotherapy, suggesting that patients should receive platinum rechallenge if clinically able. Disease control with platinum rechallenge was more likely with prior first-line platinum having achieved disease control, longer time since first-line platinum, and absence of liver metastases.
BACKGROUND: Fit patients with metastatic urothelial carcinoma (mUC) receive first-line platinum-based combination chemotherapy (fPBC) as standard of care and may receive additional later-line chemotherapy after progression. Our study compares outcomes with subsequent platinum-based chemotherapy (sPBC) versus subsequent non-platinum-based chemotherapy (sNPBC). MATERIALS AND METHODS: Patients from 27 international centers in the Retrospective International Study of Cancers of the Urothelium (RISC) who received fPBC for mUC and at least two cycles of subsequent chemotherapy were included in this study. A multivariable Cox proportional hazards model compared overall survival (OS) and progression-free survival (PFS). RESULTS: One hundred thirty-five patients received sPBC and 161 received sNPBC. Baseline characteristics were similar between groups, except patients who received sPBC had higher baseline hemoglobin, higher disease control rate with fPBC, and longer time since fPBC. OS was superior in the sPBC group (median 7.9 vs 5.5 months) in a model adjusting for comorbidity burden, performance status, liver metastases, number of fPBC cycles received, best response to fPBC, and time since fPBC (hazard ratio, 0.72; 95% confidence interval, 0.53-0.98; p = .035). There was no difference in PFS. More patients in the sPBC group achieved disease control than in the sNPBC group (57.4% vs 44.8%; p = .041). Factors associated with achieving disease control in the sPBC group but not the sNPBC group included longer time since fPBC, achieving disease control with fPBC, and absence of liver metastases. CONCLUSION: After receiving fPBC for mUC, patients who received sPBC had better OS and disease control. This may help inform the choice of subsequent chemotherapy in patients with mUC. IMPLICATIONS FOR PRACTICE: Patients with progressive metastatic urothelial carcinoma after first-line platinum-based combination chemotherapy may now receive immuno-oncology agents, erdafitinib, enfortumab vedotin, or sacituzumab govitecan-hziy; however, those ineligible for these later-line therapies or who progress after receiving them may be considered for subsequent chemotherapy. In this retrospective study of 296 patients, survival outcomes and disease control rates were better in those receiving subsequent platinum-based rechallenge compared with non-platinum-based chemotherapy, suggesting that patients should receive platinum rechallenge if clinically able. Disease control with platinum rechallenge was more likely with prior first-line platinum having achieved disease control, longer time since first-line platinum, and absence of liver metastases.
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Authors: Olivia A Do; Lorin A Ferris; Sarah K Holt; Jorge D Ramos; Lauren C Harshman; Elizabeth R Plimack; Simon J Crabb; Sumanta K Pal; Ugo De Giorgi; Sylvain Ladoire; Jack Baniel; Andrea Necchi; Ulka N Vaishampayan; Aristotelis Bamias; Joaquim Bellmunt; Sandy Srinivas; Tanya B Dorff; Matt D Galsky; Evan Y Yu Journal: Clin Genitourin Cancer Date: 2020-11-12 Impact factor: 2.872
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Authors: Yohann Loriot; Andrea Necchi; Se Hoon Park; Jesus Garcia-Donas; Robert Huddart; Earle Burgess; Mark Fleming; Arash Rezazadeh; Begoña Mellado; Sergey Varlamov; Monika Joshi; Ignacio Duran; Scott T Tagawa; Yousef Zakharia; Bob Zhong; Kim Stuyckens; Ademi Santiago-Walker; Peter De Porre; Anne O'Hagan; Anjali Avadhani; Arlene O Siefker-Radtke Journal: N Engl J Med Date: 2019-07-25 Impact factor: 91.245
Authors: Jonathan E Rosenberg; Peter H O'Donnell; Arjun V Balar; Bradley A McGregor; Elisabeth I Heath; Evan Y Yu; Matthew D Galsky; Noah M Hahn; Elaina M Gartner; Juan M Pinelli; Shang-Ying Liang; Amal Melhem-Bertrandt; Daniel P Petrylak Journal: J Clin Oncol Date: 2019-07-29 Impact factor: 44.544