Examining Pembrolizumab Combo Safety in High-Risk Prostate Cancer

In a conversation with CancerNetwork^®, Zin Myint, MD, associate professor of Internal Medicine specializing in genitourinary malignancies at the Markey Cancer Center of the University of Kentucky, discussed the background behind a presentation she gave at the 2026 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium, which compared the safety outcomes of pembrolizumab (Keytruda) and radiation with or without olaparib (Lynparza) among patients with high-risk prostate cancer.

She initially expressed that patients diagnosed with high-risk localized disease are more likely to experience recurrence, metastatic disease, or prostate-specific mortality, highlighting that intensification of treatment with PARP inhibition, immunotherapy, and radiation may improve outcomes and mitigate risks for these patients.

Myint further outlined the design of the phase 2 study (NCT05568550), which assessed a pembrolizumab backbone with standard-of-care radiation and hormone therapy plus long-term dosing of olaparib. To address limited safety data for this combination, her team presented the analysis at conference.

Findings from the presentation showed that pembrolizumab plus radiation therapy and hormone therapy was feasible and tolerable among patients. Additionally, olaparib did not add any high-grade toxicity, although low-grade urinary events were more common among those who received this agent.

Transcript:

[Patients with] localized, high-risk, and very high-risk prostate cancer substantially [increase their] risk of recurrent disease and biochemical recurrence. Subsequently, [they] can develop metastasis and prostate-specific mortality. The treatment intensification strategies are a need for these populations. Preclinically, there's a strong synergy between PARP inhibition, immunotherapy, and radiation.

We designed a study looking at the phase 2 randomized trial [evaluating] pembrolizumab combined with olaparib combined with the standard-of-care treatment—which is radiation with long-term hormone therapy—vs pembrolizumab with the standard-of-care treatment, radiation and hormone treatment. There are limited data on the safety of the combination with pembrolizumab and radiation or pembrolizumab plus olaparib with the radiation in prostate cancer. This is a prespecified safety analysis for the population.

Reference

Myint Z, Yan D, Strup S, et al. Interim safety analysis of a randomized phase II trial comparing pembrolizumab with radiation versus pembrolizumab, olaparib, and radiation in localized high risk prostate cancer. J Clin Oncol. 2026;44(suppl 7):362. doi:10.1200/JCO.2026.44.7_suppl.362