Pembrolizumab for MSI-H or dMMR (Category 2B).

Merck...announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with...unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy.

...One year PSA (Prostate Specific Antigen) failure rate`Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v4.0`Number of participants with decrease in SUV uptake after 3 cycles of pembrolizumab`Assess a possible correlation between deficient mismatched repair (dMMR) and microsatellite instability-high (MSI-H) and response to pembrolizumab.`...

Nineteen of 65 patients with dMMR metastatic castration-resistant prostate cancer were treated with anti-PD1 therapy. The PSA50 response rate was 65%, and the median progression-free survival (PFS) was 24 (95% confidence interval 16-54) weeks...

In C1-C3, TMB was associated with PSA response (one-sided nominal P = 0.0016) and time to PSA progression (one-sided nominal P = 0.00092). In C1-C3, PD-L1 CPS was associated with PSA response (one-sided nominal P = 0.046) and time to PSA progression (one-sided nominal P = 0.021)....In C1-C3, MSI was associated with PSA response (one-sided nominal P = 0.019).

Retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) and MSI-H tumor detected by a commercially available cfDNA NGS assay Guardant360 (G360, Guardant Health) at eight different Academic Institutions in the USA, from September 2018 to April 2020. From a total of 14 MSI-H metastatic prostate cancer patients at participating centers, nine patients with mCRPC with 56% bone, 33% nodal, 11% liver and 11% soft-tissue metastases and a median PSA of 29.3 ng/dL, were treated with pembrolizumab after 2 lines of therapy for CRPC. The estimated median time on pembrolizumab was 9.9 (95% CI 1.0 to 18.8) months.

At present 11 CRPC patients were included in the program and treated with nivolumab (n = 4) and pembrolizumab (n = 7)….Biochemical PSA ( > 50%) responses were seen in both MSI and PDL1 positive patients….Encouraging responses to anti-PD1 checkpoint immunotherapy were seen in CRPC patients selected for PDL1-positivity and MSI.

Eleven patients with MSI-H/dMMR castration-resistant prostate cancer received anti–PD-1/PD-L1 therapy. Six of these (54.5%) had a greater than 50% decline in prostate-specific antigen levels, 4 of whom had radiographic responses….Our results demonstrate that anti–PD-1/PD-L1 therapy is associated with meaningful clinical benefit in nearly half of MSI-H/dMMR mCRPC.

Here, in this report, we present a case of a patient with mCRPC harboring a somatic dMMR who had progressed on pembrolizumab after an initial response. He enrolled on a clinical trial with JNJ-081, a prostate-specific membrane antigen-CD3 bispecific T-cell engager antibody and experienced a partial response with course complicated by cytokine release syndrome. On progression, he was reinitiated on pembrolizumab and experienced an exceptional second response, with his prostate-specific antigen falling from a high of 20.01 to undetectable after 6 weeks and remaining undetectable for >11 months.

This is a case of a 66-year-old Asian male patient with prostate adenocarcinoma who had metastases at initial presentation….Subsequently, microsatellite instability-high was detected, and pembrolizumab was administered resulting in complete remission with the resolution of symptoms and continued therapeutic effect for more than 14 months.

We report 2 patients with metastatic castration-resistant prostate cancer (mCRPC) who had prior treatment with multiple lines of therapy and underwent ctDNA testing, which detected MSI-H status. Both patients were treated with pembrolizumab, resulting in an excellent clinical response measured with liquid biopsies before and after initiation of therapy...