Immunotherapy is not currently a major part of the treatment armamentarium for advanced prostate cancer, as there are few patients who benefit from this type of treatment. Ongoing research is examining strategies that may change this in the future. Findings from studies evaluating novel immunotherapies and strategies in advanced prostate cancer were presented at the ESMO Congress 2024.

Following these presentations, featured expert Matthew R. Smith, MD, PhD, was interviewed by Conference Reporter Associate Editor-in-Chief Christopher Ontiveros, PhD. Dr Smith’s clinical perspectives on these data are presented here.

Historically, prostate cancer has been viewed as being relatively resistant to immunotherapy compared with some other cancers. There have been many attempts to evaluate immunotherapy in prostate cancer, including ICIs, that, for the most part, have been largely disappointing in unselected patients. This is mainly because mismatch repair deficiency (dMMR) occurs in only 1% to 3% of prostate cancers, which is dramatically lower than in many other cancers. If you treat an unselected group of patients with immunotherapy, you would expect to see very few responses because of the low proportion of patients with dMMR.

The ICI pembrolizumab has broad US Food and Drug Administration (FDA) approval for patients with solid tumors that are unresectable or metastatic if they have received prior treatment and have microsatellite instability (MSI)-high disease or dMMR. This indication was based on findings from basket studies that included very few patients with prostate cancer.

At the ESMO Congress 2024, an abstract by Sandra Van Wilpe and colleagues reported on a multicenter retrospective study of the efficacy of anti–PD-L1 or anti–PD-1 therapy in 71 patients with MSI-high metastatic castration-resistant prostate cancer (mCRPC; abstract 1630P). In 52 patients with prostate-specific antigen (PSA) data, PSA50 and PSA90 responses were seen in 60% and 46% of patients, respectively. In 62 RECIST 1.1–evaluable patients, the objective response rate was 48%. Further, the 1-, 2-, and 3-year progression-free survival rates were 40.4%, 25.4%, and 22.9%, respectively. I believe that this information about the response to PD-1–targeted therapies provides us with more confidence about their use in patients with dMMR.

An abstract presented at the ESMO Congress 2024 by Niven Mehra, MD, PhD, and colleagues reported on data from a single-arm, phase 2 trial evaluating the combination of nivolumab and ipilimumab in patients with mCRPC with a spectrum of molecular alterations that might predict response to immunotherapy (abstract LBA72). The majority of the subgroup of patients who had dMMR reached a disease control rate of greater than 6 months, highlighting the importance of the dMMR biomarker for immunotherapy in prostate cancer.

Other immunologic approaches could be successful. Part of the promise of bispecific T-cell engagers is to provide immunologic-based therapy without a requirement for dMMR, and a variety of these agents are in development. At the ESMO Congress 2024, initial results were presented from a phase 1 trial evaluating xaluritamig, a STEAP1 bispecific T-cell engager, in patients with mCRPC (abstract 1598P). There was promising evidence of activity in this trial. In addition, data from a phase 1 study of JANX007 have been very encouraging and warrant its further development. I believe that there will be continued development of immunotherapy in prostate cancer and am hopeful that some of these therapies will be successful so that we will have more options for patients.