TY - JOUR
T1 - Sequencing of PD-1/L1 Inhibitors and Carboplatin Based Chemotherapy for Cisplatin Ineligible Metastatic Urothelial Carcinoma
AU - Wei, Xiao X.
AU - Werner, Lillian
AU - Teo, Min Y.
AU - Rosenberg, Jonathan E.
AU - Koshkin, Vadim S.
AU - Grivas, Petros
AU - Szabados, Bernadett
AU - Morrison, Laura
AU - Powles, Thomas
AU - Carril-Ajuria, Lucia
AU - Castellano, Daniel
AU - Velho, Pedro Isaacsson
AU - Hahn, Noah M.
AU - McKay, Rana R.
AU - Raggi, Daniele
AU - Necchi, Andrea
AU - Kanesvaran, Ravindran
AU - Alerasool, Parissa
AU - Gaines, Jacob
AU - Galsky, Matthew
AU - Bellmunt, Joaquim
AU - Sonpavde, Guru
N1 - Publisher Copyright:
© 2021 Lippincott Williams and Wilkins. All rights reserved.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
KW - carboplatin
KW - carcinoma
KW - programmed cell death 1 receptor
KW - transitional cell
KW - urinary bladder neoplasms
UR - http://www.scopus.com/inward/record.url?scp=85100125384&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85100125384&partnerID=8YFLogxK
U2 - 10.1097/JU.0000000000001371
DO - 10.1097/JU.0000000000001371
M3 - Article
C2 - 32935617
AN - SCOPUS:85100125384
SN - 0022-5347
VL - 205
SP - 414
EP - 419
JO - Journal of Urology
JF - Journal of Urology
IS - 2
ER -