TY - JOUR
T1 - Impact of prior chemotherapy on response to second-line pembrolizumab in urothelial cancer
T2 - exploratory analysis of the Phase 3 KEYNOTE-045 trial
AU - de Wit, Ronald
AU - Vaughn, David J.
AU - Fradet, Yves
AU - Fong, Lawrence
AU - Climent, Miguel A.
AU - Necchi, Andrea
AU - Petrylak, Daniel P.
AU - Gerritsen, Winald R.
AU - Gurney, Howard
AU - Quinn, David I.
AU - Culine, Stéphane
AU - Sternberg, Cora N.
AU - Bajorin, Dean F.
AU - Choueiri, Toni K.
AU - Xu, Jin
AU - Imai, Kentaro
AU - Homet Moreno, Blanca
AU - Bellmunt, Joaquim
AU - Lee, Jae-Lyun
PY - 2024/8/22
Y1 - 2024/8/22
N2 - Background and objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy. Methods: Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m2], docetaxel [75 mg/m2], or vinflunine [320 mg/m2], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response. Key findings and limitations: An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing. Conclusions and clinical implications: When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC.
AB - Background and objective: Until recently, the standard first-line treatment for advanced urothelial carcinoma (UC) was platinum-based combination chemotherapy followed by avelumab maintenance therapy for patients without progressive disease (PD). For patients with advanced UC who experience PD or recurrence, standard-of-care treatment is pembrolizumab monotherapy based on the phase 3 KEYNOTE-045 study. This post hoc analysis of the KEYNOTE-045 study evaluated the efficacy of pembrolizumab compared with chemotherapy by the best response to prior platinum-based chemotherapy. Methods: Patients with advanced UC that progressed or recurred after first-line platinum-based chemotherapy were randomly assigned 1:1 to receive either pembrolizumab 200 mg every 3 wk (Q3W) for ≤2 yr or investigator's choice of chemotherapy (paclitaxel [175 mg/m2], docetaxel [75 mg/m2], or vinflunine [320 mg/m2], each Q3W). Endpoints included overall survival (OS) from the initiation of the last treatment prior to death, objective response rate (ORR), and duration of response (DOR) as per Response Evaluation Criteria in Solid Tumors version 1.1 from the date of the first response. Key findings and limitations: An objective response to pembrolizumab was observed in all groups in terms of a prior response to first-line platinum-based chemotherapy. Median OS, ORR, and median DOR were numerically greater with pembrolizumab than with chemotherapy across subgroups. Patients with PD as the best response to prior platinum-based chemotherapy had the poorest OS outcomes. Limitations include a lack of formal hypothesis testing. Conclusions and clinical implications: When compared with chemotherapy, prolonged OS and durable responses to second-line pembrolizumab were observed independently of the response to or type of prior platinum-based chemotherapy. These findings further support pembrolizumab as second-line treatment for advanced UC.
KW - Chemotherapy
KW - Pembrolizumab
KW - Programmed cell death 1
KW - Urothelial carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85202209225&partnerID=8YFLogxK
U2 - 10.1016/j.eururo.2024.07.015
DO - 10.1016/j.eururo.2024.07.015
M3 - Article
C2 - 39174409
AN - SCOPUS:85202209225
SN - 0302-2838
JO - European Urology
JF - European Urology
ER -