Background
The utilization of immune checkpoint inhibitors (ICI) in prostate cancer (PC) can be very effective for patients with mismatch repair-deficiency (as identified by MSI-H by PCR/NGS or dMMR IHC). The use of ICI in this patient population has been associated with high rates of durable response. There is limited published data on factors that may influence patient response and outcomes. The aim of this study is to describe the utilization of and tumor response to ICI in this patient population.
Methods
This is a retrospective study of men with MSI-H PC reported by somatic genomic testing from April 1, 2015 to March 31, 2022 through the VA National Precision Oncology Program (NPOP), who received at least one dose of ICI. The primary objectives are to describe the incidence of MSI-H PC and the utilization of ICI. Descriptive statistics and Kaplan- Meier estimator were used for secondary objectives to determine the prostate-specific antigen decline of at least 50% (PSA50), clinical progression free survival (cPFS), time on ICI as a function of number of prior therapies, the extent of metastasis prior to initiation of ICI, and the correlation of MMR genetic alterations with treatment response.
Results
66 patients with MSI-H PC were identified (1.5% of a total of 4267 patients with PC tested through NPOP). 23 patients (35%) received at least one dose of ICI. 12 of 23 patients (52%) had PSA response. PSA50 responses occurred in 6 patients (50%) and 5 continued to have durable PSA50 at six months. Median cPFS was 280 days (95% CI: 105 days-not reached) and the estimated PFS at six months was 72.2% (95% CI: 35.7%-90.2%). 8 of 12 (67%) responders have received multiple lines of therapy for M1 PC. 8 of 12 patients (67%) had high-volume disease at ICI initiation. Of those patients with a MMR genetic alteration, patients with MLH1 (3/3) and MSH2 (6/8) alterations responded more frequently than those with MSH6 alterations (1/4).
Conclusions
MSI-H PC is rare but response rates to ICI are high and durable. Patients with MLH1 and MSH2 alterations appeared to respond more frequently than those with MSH6. Additional follow-up is ongoing.
