Men with prostate cancer harboring the MMRd mutation may benefit significantly from dual immunotherapy using immune checkpoint inhibitors, according to a recent study published in the Annals of Oncology. The research highlights a specific genetic profile that predicts a favorable response to immunotherapy, offering new hope for a subset of patients with this challenging disease.
The study, led by Niven Mehra, MD, PhD, from Radboud University Medical Center, assessed the response of men with four different prostate cancer tumor mutations—MMRd, hTMB, BRCAm, and CDK12i—to treatment with ipilimumab and nivolumab. These mutations account for approximately 15% of all prostate cancer cases.
The primary endpoint of the phase II trial was the disease control rate at six months. The most promising results were observed in patients with the MMRd tumor type, where the disease control rate reached 81%. In contrast, the disease control rates for hTMB, CDK12i, and BRCAm were 25%, 19%, and 15%, respectively.
Progression-Free and Overall Survival
Median progression-free survival (PFS) varied significantly across the groups. The hTMB, CDK12i, and BRCAm groups had PFS of 3.8, 1.6, and 3.5 months, respectively. The MMRd group, however, demonstrated a remarkable PFS of 32.7 months. Median overall survival (OS) was 10.3, 10.3, and 7.1 months in the hTMB, CDK12i, and BRCAm groups, respectively, while the MMRd group's OS ranged from 24.8 months to not reached.
Clinical Implications
"It’s not a large group, but for these patients, immunotherapy can significantly slow the progression of prostate cancer," said lead author Sandra van Wilpe. "We see that with immunotherapy, the cancer remains controlled for 33 months, which is a remarkable result."
The findings suggest that identifying patients with the MMRd mutation could help personalize treatment strategies and improve outcomes for a subset of men with prostate cancer. Further research is needed to validate these results in larger cohorts and to explore the underlying mechanisms driving the response to immunotherapy in MMRd-mutated tumors.
