PURPOSE: Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval1L-2L) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival. RESULTS: In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.
PURPOSE: Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval1L-2L) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival. RESULTS: In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.
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Authors: Arjun V Balar; Matthew D Galsky; Jonathan E Rosenberg; Thomas Powles; Daniel P Petrylak; Joaquim Bellmunt; Yohann Loriot; Andrea Necchi; Jean Hoffman-Censits; Jose Luis Perez-Gracia; Nancy A Dawson; Michiel S van der Heijden; Robert Dreicer; Sandy Srinivas; Margitta M Retz; Richard W Joseph; Alexandra Drakaki; Ulka N Vaishampayan; Srikala S Sridhar; David I Quinn; Ignacio Durán; David R Shaffer; Bernhard J Eigl; Petros D Grivas; Evan Y Yu; Shi Li; Edward E Kadel; Zachary Boyd; Richard Bourgon; Priti S Hegde; Sanjeev Mariathasan; AnnChristine Thåström; Oyewale O Abidoye; Gregg D Fine; Dean F Bajorin Journal: Lancet Date: 2016-12-08 Impact factor: 79.321
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: Manish R Patel; John Ellerton; Jeffrey R Infante; Manish Agrawal; Michael Gordon; Raid Aljumaily; Carolyn D Britten; Luc Dirix; Keun-Wook Lee; Mathew Taylor; Patrick Schöffski; Ding Wang; Alain Ravaud; Arnold B Gelb; Junyuan Xiong; Galit Rosen; James L Gulley; Andrea B Apolo Journal: Lancet Oncol Date: 2017-12-05 Impact factor: 41.316