@article{afd47cf320c945d7a3b9983edf0b38a6,
title = "Pembrolizumab in men with heavily treated metastatic castrate-resistant prostate cancer",
abstract = "Background: Pembrolizumab is approved for patients with metastatic, microsatellite instability (MSI)-high or mismatch repair-deficient (dMMR) solid tumors. However, very few men with prostate cancer were included in these initial studies. Methods: We performed a single institution retrospective review of men with metastatic castrate-resistant prostate cancer (mCRPC) who were treated with pembrolizumab. The primary objective was to describe the clinical efficacy of pembrolizumab associated with patient and genomic characteristics. Results: We identified 48 men who received ≥1 cycle of pembrolizumab for mCRPC. Of these, 94% (45/48) had ≥3 prior lines of therapy for mCRPC. Somatic tumor sequencing was available in 18/48 men (38%). We found that 17% (8/48) had a ≥50% confirmed PSA decline with pembrolizumab, and 8% (4/48) had a ≥90% PSA decline with durations of response ranging from 3.1 to 16.3 months. Two of these four men had mutations in LRP1b, one of whom also had MSH2 loss and was MSI-H and TMB-high. Despite prior progression on enzalutamide, 48% (23/48) of men were treated with concurrent enzalutamide. The median PSA progression-free-survival was 1.8 months (range 0.4-13.7 months), with 31% of patients remaining on pembrolizumab therapy and 54% of men remain alive with a median follow-up of 7.1 months. Conclusions: In a heavily pretreated population of men with mCRPC, pembrolizumab was associated with a ≥50% PSA decline in 17% (8/48) of men, including a dramatic ≥90% PSA response in 8% (4/48), two of whom harbored pathogenic LRP1b mutations suggesting that LRP1b mutations may enrich for PD-1 inhibitor responsiveness in prostate cancer.",
keywords = "LRP1b, genomic profiling, mCRPC, pembrolizumab, prostate cancer",
author = "Tucker, {Matthew D.} and Jason Zhu and Daniele Marin and Gupta, {Rajan T.} and Santosh Gupta and Berry, {William R.} and Sundhar Ramalingam and Tian Zhang and Michael Harrison and Yuan Wu and Patrick Healy and Stacey Lisi and George, {Daniel J.} and Armstrong, {Andrew J.}",
note = "Funding Information: Jason Zhu reports personal fees from Bayer, outside the submitted work. Tian Zhang reports grants from Acerta, Novartis, Merrimack, Abbvie/Stemcentrx, Merck, Regeneron, Exelixis, Janssen, Pfizer, OmniSeq, and Personal Genome Diagnostics; services on speaker's bureau and advisory boards for Genentech/Roche, Exelixis, Sanofi‐Aventis; services on advisory board for Janssen, Astra Zeneca, Pfizer, Amgen, Bristol Myers Squibb (BMS); consultant services for Bayer, AstraZeneca, and Foundation Medicine; spouse is an employee and stockholder for Capio Biosciences all outside the submitted work. Michael Harrison reports grants from Merck, Genentech, AstraZeneca, Pfizer, BMS, and Janssen; personal feeds from Bayer, Genentech, AstraZeneca, Pfizer, BMS, and Janssen, all outside the submitted work. Daniel J. George reports grants from Janssen, Astellas/Pfizer, Dendreon, Bayer, Novartis, BMS, and Genentech/Roche; personal fees from Janssen, Astellas/Pfizer, Bayer, Merck, BMS, and Genetech/Roche; consulting services for Janssen, Astellas/Pfizer, Bayer, Merck, BMS, and Genentech/Roche, all outside the submitted work. Andrew J. Armstrong reports grants from Janssen, Astellas/Pfizer, Dendreon/San Power, Bayer, Novartis, Merck, BMS, Genetch/Roche, Active Biotech, Constellation, and AstraZenica; personal fees from Janssen, Astellas/Pfizer, Dendreon/San Power, Bayer, and Merck; consulting services for Janssen, Astellas/Pfizer, Dendreon/San Power, Bayer, Merck, and AstraZenica, all outside the submitted work. Matthew D. Tucker, Daniele Marin, Rajan T. Gupta, Santosh Gupta, William R. Berry, Sundhar Ramalingam, Yuan Wu, Patrick Healy, and Stacey Lisi collectively have no disclosures to report. Publisher Copyright: {\textcopyright} 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.",
year = "2019",
month = aug,
doi = "10.1002/cam4.2375",
language = "English (US)",
volume = "8",
pages = "4644--4655",
journal = "Cancer Medicine",
issn = "2045-7634",
publisher = "John Wiley and Sons Ltd",
number = "10",
}