Randomized Phase II Study of Durvalumab with or without Tremelimumab in Patients with Metastatic Castration Resistant Prostate Cancer.

Autor:	Winquist E; Western Caspian University, London, Ontario, Canada., Hotte SJ; Hamilton Health Sciences, Hamilton, Ontario, Canada., Chi K; BC Cancer, Vancouver, British Columbia, Canada., Sridhar S; Princess Margaret Hospital, Toronto, ON, Canada., Ellard S; BC Cancer Kelowna, Kelowna, British Columbia, Canada., Ong M; The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada., Iqbal N; Saskatoon Cancer Centre, Canada., Salim M; Allan Blair Cancer Centre, Regina, Saskatchewan, Canada., Emmenegger U; Sunnybrook Research Institute, Toronto, Ontario, Canada., Gingerich JR; University of Manitoba, Winnipeg, MB, Canada., Lalani AK; Juravinski Cancer Centre, Hamilton, Canada., Major P; Hamilton Health Sciences, Hamilton, Canada., Kollmannsberger C; BC Cancer Agency, Vancouver, British Columbia, Canada., Yip S; Tom Baker Cancer Centre, Calgary, AB, Canada., Hansen A; Princess Margaret Hospital, Brisbane, Queensland, Australia., Finch D; BC Cancer Cancer Centre for the Southern Interior, Kelowna, BC, Canada., Canil C; Ottawa Hospital Research Institute, Ottawa, ON, Canada., Hutchenreuther J; Queen's University, Kingston, ON, Canada., Vera-Badillo F; Kingston Health Sciences Centre, Canada., Smoragiewicz M; Sunnybrook Health Science Centre, Toronto, Ontario, Canada., Cabanero M; University Health Network, Toronto, Ontario, Canada., Tsao MS; University of Toronto, Toronto, Ontario, Canada., Ritch E; University of British Columbia, Vancouver, British Columbia, Canada., Wyatt AW; University of British Columbia, Vancouver, British Columbia, Canada., Seymour L; Queen's University, Kingston, Ontario, Canada.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI:	10.1158/1078-0432.CCR-24-1612
Abstrakt:	Purpose: Programmed death-ligand 1 (PD-L1) is overexpressed by dendritic cells in patients with metastatic castration-resistant prostate cancer (mCRPC) progressing on androgen receptor pathway inhibitors. We tested whether checkpoint blockade could enhance antitumor activity in mCRPC. Methods: In a multicenter open-label non-comparative randomized phase II study, patients with mCRPC treated with £ 1 prior cytotoxic chemotherapy, with measurable disease and progression on abiraterone and/or enzalutamide were randomized to durvalumab (D) 1500mg IV Q4 weeks ± 4 doses of tremelimumab (T) 75mg IV. The primary endpoint was objective response (OR) by iRECIST using a Simon 2-stage design. Correlative testing included PD-L1/CD8 immunohistochemistry on baseline tumour biopsies and deep targeted sequencing of plasma cell-free DNA. Results: 52 patients were enrolled. Median age was 70 years (range, 50-83 years) and 52% had prior taxane therapy for mCRPC. In stage 1, 13 patients were randomized to D with no OR observed. D+T advanced to stage 2 with 39 patients enrolled (receiving a median 3 cycles, range 1-53). D+T related adverse events (AEs) were mainly £ grade 2 but led to discontinuation in 7 patients . There were seven OR (19.4% [95% confidence interval: 8.2-36.0%]; intention to treat (ITT) 17.9% [95% confidence interval: 7.5-33.5%]). Five responding tumours were PD-L1 positive and two exhibited DNA damage repair defects. Responses were observed without high tumour mutational burden or other genomic indices of immunotherapy sensitivity. Conclusion: D+T is active in mCRPC but patient selection remains a challenge. Further studies to develop predictive biomarkers are warranted.
Databáze:	MEDLINE
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