A Case of Locally Advanced Castration-resistant Prostate Cancer With Remarkable Response to Nivolumab

Basnet, Alina; Khullar, Gaurav; Mehta, Rashi I.; Chittoria, Namita

doi:10.1016/j.clgc.2017.05.005

Cited by 7 publications

(11 citation statements)

References 22 publications

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“…The current PC-related medical literature describes a few PD-1 axis checkpoint inhibitor therapy successes with some highly promising results with pembrolizumab monotherapy. [1][2][3][4][5]7,11,12 The recent approval of pembrolizumab for MSI-H solid neoplasms is the only current indication for ICI therapy in PC. Despite these encouraging results, additional immune-related targets are needed.…”

Section: Discussionmentioning

confidence: 99%

“…6 However, a CRPC patient with MSH2 and MSH6 loss in his neoplasm was reported to have had a robust response to nivolumab. 7 Microsatellite instability is a promising predictor of immunotherapy response in PC with 1-2% of PC having microsatellite instability, 8,9 which makes them eligible for pembrolizumab therapy. 10 The most substantial checkpoint inhibition results have been observed with pembrolizumab.…”

Section: Introductionmentioning

confidence: 99%

“…In a phase 1 trial with nivolumab, 17 patients with CRPCs had no objective response . However, a CRPC patient with MSH2 and MSH6 loss in his neoplasm was reported to have had a robust response to nivolumab . Microsatellite instability is a promising predictor of immunotherapy response in PC with 1‐2% of PC having microsatellite instability, which makes them eligible for pembrolizumab therapy .…”

Section: Introductionmentioning

confidence: 99%

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Identification of targets for prostate cancer immunotherapy

et al. 2019

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Background We performed profiling of the immune microenvironment of castration‐resistant (CRPC) and castration‐sensitive (CSPC) prostate cancer (PC) in order to identify novel targets for immunotherapy. Methods PD‐L1 and CD3/CD8 immunohistochemistry, PD‐L1/2 fluorescent in situ hybridization, tumor mutation burden, microsatellite instability, and RNA‐seq of 395 immune‐related genes were performed in 19 CRPC and CSPC. Targeted genomic sequencing and fusion analysis were performed in 17 of these specimens. Results CD276, PVR, and NECTIN2 were highly expressed in PC. Comparison of CRPC versus CSPC and primary versus metastatic tissue revealed the differential expression of immunostimulatory, immunosuppressive, and epithelial‐to‐mesenchymal transition (EMT)‐related genes. Unsupervised clustering of differentially expressed genes yielded two final clusters best segregated by CRPC and CSPC status. Conclusion CD276 and the alternative checkpoint inhibition PVR/NECTIN2/CD226/TIGIT pathway emerged as relevant to PC checkpoint inhibition target development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Identification of targets for prostate cancer immunotherapy

et al. 2019

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“…The initial trials of immune checkpoint inhibitors in unselected prostate cancer patients (66–68) demonstrated no global clinical benefit in prostate cancer. Nevertheless, interest in such therapies remained strong, given case reports of impressive and durable responses among individual prostate cancer patients (69, 70). Experiences from other tumor types illuminated patient subtypes that may derive clinical benefit from existing therapies.…”

Section: Prostate Tumor Mutation Burden Dna Repair Defects and Thermentioning

confidence: 99%

Genomic Alteration Burden in Advanced Prostate Cancer and Therapeutic Implications

Ryan

Bose

2019

Front. Oncol.

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The increasing number of patients with sequenced prostate cancer genomes enables us to study not only individual oncogenic mutations, but also capture the global burden of genomic alterations. Here we review the extent of tumor genome mutations and chromosomal structural variants in various clinical states of prostate cancer, and the related prognostic information. Next, we discuss the underlying mutational processes that give rise to these various alterations, and their relationship to the various molecular subtypes of prostate cancer. Finally, we examine the relationships between the tumor mutation burden of castration-resistant prostate cancer, DNA repair defects, and response to immune checkpoint inhibitor therapy.

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“…MMRd cancer is more prone to respond to monotherapy anti-PD-1/PD-L1 ICB [14,15]. A handful reports corroborated responsiveness of ICB in MMRd prostate cancer [5,8,14,16,17] with biochemical responses witnessed in over half of patients. DNA-damage repair defects (including homologous recombination defects in genes including BRCA1, BRCA2, ATM, CHEK2) and those with instable chromosomal prostate cancer (particular biallelic CDK12 aberrations) [12,14,18], define mutational subtypes of mCRPC that could be enriched for in future trials with IBC.…”

mentioning

confidence: 99%