Sequencing of PD-1/L1 Inhibitors and Carboplatin-Based Chemotherapy for Cisplatin-Ineligible Metastatic Urothelial Carcinoma.

Current first-line treatment options in patients with metastatic urothelial carcinoma (mUC) unfit to receive cisplatin-containing chemotherapy include PD-1/L1 inhibitors and carboplatin-containing chemotherapy. However, the optimal sequencing of these therapies remains unclear.

We conducted a multicenter retrospective analysis. Consecutive cisplatin-ineligible patients with mUC 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 (TTF1) and second-line (TTF2) therapy, interval between end of first-line and initiation of second-line treatment (Interval1L-2L), and overall survival (OS) were collected. Multivariate analysis was conducted to examine the association of sequencing on OS.

In this multicenter retrospective study, we identified 146 cisplatin-ineligible patients with mUC treated with first-line (1L) PD-1/L1 inhibitor therapy followed by second-line (2L) carboplatin-containing chemotherapy (Group 1, n=43) or the reverse sequence (Group 2, n=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% 1L, 44.2% 2L) compared to PD-1/L1 inhibitors (9.3% 1L, 21.3% 2L). 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).

In this biomarker-unselected cohort of cisplatin-ineligible patients with mUC, PD-1/L1 inhibitor followed by carboplatin-containing chemotherapy and the reverse sequence had comparable OS.

The Journal of urology. 2020 Sep 16 [Epub ahead of print]

Xiao X Wei, Lillian Werner, Min Y Teo, Jonathan E Rosenberg, Vadim S Koshkin, Petros Grivas, Bernadett Szabados, Laura Morrison, Thomas Powles, Lucia Carril-Ajuria, Daniel Castellano, Pedro Isaacsson Velho, Noah M Hahn, Rana R McKay, Daniele Raggi, Andrea Necchi, Ravindran Kanesvaran, Parissa Alerasool, Jacob Gaines, Matthew Galsky, Joaquim Bellmunt, Guru Sonpavde

Dana-Farber Cancer Institute, Boston, Massachusetts., Memorial Sloan Kettering Cancer Center, New York, New York., University of California San Francisco, Francisco, California., University of Washington School of Medicine and Fred Hutchinson Cancer Research Center, Seattle, Washington., Barts Cancer Centre, Queen Mary University of London, London, United Kingdom., Universitario 12 de Octubre, Madrid, Spain., Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland., University of California San Diego, La Jolla, California., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., National Cancer Centre Singapore, Singapore., Tisch Cancer Institute at Mount Sinai, New York, New York.