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Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial

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Abstract
Purpose: There is an unmet need for therapeutic options that prolong survival for patients with heavily pretreated, metastatic castration-resistant prostate cancer (mCRPC). The phase III, open-label KEYLYNK-010 study evaluated pembrolizumab plus olaparib versus a next-generation hormonal agent (NHA) for biomarker-unselected, previously treated mCRPC.

Methods: Eligible participants had mCRPC that progressed on or after abiraterone or enzalutamide (but not both) and docetaxel. Participants were randomly assigned (2:1) to pembrolizumab plus olaparib or NHA (abiraterone or enzalutamide). The dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group-modified RECIST 1.1 and overall survival (OS). Time to first subsequent therapy (TFST) was a key secondary end point. Safety and objective response rate (ORR) were secondary end points.

Results: Between May 30, 2019, and July 16, 2021, 529 participants were randomly assigned to pembrolizumab plus olaparib and 264 to NHA. At final rPFS analysis, median rPFS was 4.4 months (95% CI, 4.2 to 6.0) with pembrolizumab plus olaparib and 4.2 months (95% CI, 4.0 to 6.1) with NHA (hazard ratio [HR], 1.02 [95% CI, 0.82 to 1.25]; P = .55). At final OS analysis, median OS was 15.8 months (95% CI, 14.6 to 17.0) and 14.6 months (95% CI, 12.6 to 17.3), respectively (HR, 0.94 [95% CI, 0.77 to 1.14]; P = .26). At final TFST analysis, median TFST was 7.2 months (95% CI, 6.7 to 8.1) versus 5.7 months (95% CI, 5.0 to 7.1), respectively (HR, 0.86 [95% CI, 0.71 to 1.03]). ORR was higher with pembrolizumab plus olaparib versus NHA (16.8% v 5.9%). Grade ≥3 treatment-related adverse events occurred in 34.6% and 9.0% of participants, respectively.

Conclusion: Pembrolizumab plus olaparib did not significantly improve rPFS or OS versus NHA in participants with biomarker-unselected, heavily pretreated mCRPC. The study was stopped for futility. No new safety signals occurred.

Trial registration: ClinicalTrials.gov NCT03834519.
Author(s)
Emmanuel S AntonarakisSe Hoon ParkJeffrey C GohSang Joon ShinJae Lyun LeeNiven MehraRay McDermottNúria Sala-GonzalezPeter C FongRichard GreilMargitta RetzJuan Pablo SadePatricio YanezYi-Hsiu HuangStephen D BegbieRustem Airatovich GafanovMaria De SantisEli RosenbaumMichael P KolinskyFelipe ReyKun-Yuan ChiuGuilhem RoubaudGero KramerMakoto SumitomoFrancesco MassariHiroyoshi SuzukiPing QiuJinchun ZhangJeri KimChristian H PoehleinEvan Y Yu
Issued Date
2023
Type
Article
DOI
10.1200/JCO.23.00233
URI
https://oak.ulsan.ac.kr/handle/2021.oak/16609
Publisher
JOURNAL OF CLINICAL ONCOLOGY
Language
영어
ISSN
0732-183X
Citation Volume
41
Citation Number
22
Citation Start Page
3839
Citation End Page
3850
Appears in Collections:
Medicine > Nursing
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