Immunotherapy shows promise for men with specific types of prostate cancer Genetic screening enhances effectiveness of immunotherapy

New research has shown that immunotherapy can be effective in treating prostate cancer in men who are selected based on the genetic characteristics of their tumors. In a recent study conducted at Radboud university medical center, it was found that for some men with a particular genetic type of prostate cancer, the progression of the disease was slowed down by 33 months. The study's findings were published in the Annals of Oncology.

While immunotherapy has not been widely successful for all men with prostate cancer, a closer examination of existing studies suggests that it can be highly effective for certain patients. According to oncologist Niven Mehra from Radboudumc: 'We discovered that men who responded well to immunotherapy had specific DNA errors in their tumors. These genetic abnormalities cause protein changes that activate the immune system, making immunotherapy more effective.'

Based on these findings, Mehra and his team conducted a study to test the effectiveness of immunotherapy in a group of men whose prostate cancer was characterized by specific genetic subtypes. The study targeted four different DNA subtypes—MMRd, hTMB, BRCAm, and CDK12i—found in about fifteen percent of all prostate cancer cases. A total of 69 men received a combination of two types of immunotherapy, ipilimumab and nivolumab, as part of the study.

Slow down disease

The study found that dual immunotherapy slowed the progression of prostate cancer in selected patients by four months. The most notable response was observed in patients with the MMRd mutation, where the cancer was slowed by 33 months. In some cases, this ranged from stabilizing the disease to reducing it to such an extent that it was no longer detectable in the blood or visible on scans. At the time of publication, the cancer remained under control in twenty patients.

This study did not directly compare dual immunotherapy with standard treatments, such as hormone therapy or chemotherapy. However, it is known that single immunotherapy for patients with MMRd typically keeps the disease under control for about eight months, compared to 33 months with the dual therapy tested in this study. 

Like all treatments, immunotherapy can cause side effects. Nearly half of the men in the study experienced side effects, such as diarrhea, and around twenty percent of patients discontinued treatment due to these effects. 

Early Screening

Immunotherapy is most effective in prostate cancer with MMRd, found in four to five percent of patients. 'It’s not a large group, but for these patients, immunotherapy can significantly slow the progression of prostate cancer', says clinician-scientist Sandra van Wilpe. 'We see that with immunotherapy, the cancer remains controlled for 33 months, which is a remarkable result.'

To identify men with genetic mutations, Mehra advocates for genomic diagnostic screening early in the disease, a practice already in place at the Radboudumc. Mehra explains: 'Based on our results, for men with MMRd,  it might be beneficial to consider starting immunotherapy even before hormone therapy or chemotherapy. Then you need to examine the tumor’s DNA early in the disease process. Potentially, we could cure these men with MMRd metastatic prostate cancer, though further research is needed.'

In the Netherlands, immunotherapy is currently only reimbursed for prostate cancer if a genetic test confirms the presence of MMRd. This is for single-agent immunotherapy, not the combination used in the study described here. Combination therapy is not yet available as a treatment, and there are currently no clinical trials for combination therapy in the Netherlands. For more information about genetic screening and immunotherapy, please consult your treating physician.

About the publication

This research has been published in Annals of Oncology: Ipilimumab with Nivolumab in Molecular-Selected Patients with 2 Castration-Resistant Prostate Cancer: Primary Analysis of the Phase 2 INSPIRE Trial. S. van Wilpe, I.S.H. Kloots, P.H.J. Slootbeek, M. den Brok, H. Westdorp, M.D. Franken, M. Coskunturk, T. Osinga, H. Bloemendal, G. Adema, R.J. Smeenk, J. Nagarajah, J. van Ipenburg, L.I. Kroeze, M.J.L. Ligtenberg, J. Schalken, W.R. Gerritsen, N. Mehra. DOI: 10.1016/j.annonc.2024.09.004.

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