Dr Michiel Strijbos, a GU oncologist at GZA Wilrijk, and prof. Christian Gratzke, a urologist from Freiburg, Germany, engaged in a discussion on the potential of immunotherapy in the context of prostate cancer.
Prof. Gratzke presented findings from the KEYNOTE-991 trial, which investigated enzalutamide and pembrolizumab in hormone-sensitive prostate cancer. Unfortunately, this trial yielded negative results. Furthermore, the session also featured the presentation of the KEYNOTE-641 trial involving patients with metastatic castration-resistant prostate cancer (CRPC), which also turned out to be a negative trial. These outcomes align with the results of the KEYNOTE-921 trial, which explored the combination of pembrolizumab with docetaxel, and trials involving olaparib in the CRPC setting. These four negative trials collectively indicate that immunotherapy has not demonstrated clinical benefit in the context of prostate cancer.
The KEYNOTE-991 trial specifically focused on patients with metastatic hormone-sensitive prostate cancer. They received enzalutamide and ADT, which is considered the gold standard for this patient group. Pembrolizumab was added to this regimen. However, the trial failed to show significant clinical benefits in terms of its primary endpoints, OS and radiographic PFS, when pembrolizumab was combined with enzalutamide and ADT. Notably, pembrolizumab did lead to a higher incidence of side effects. Consequently, the use of pembrolizumab in prostate cancer in this setting currently lacks support.
The discussion then shifted towards alternative immunotherapy strategies that could potentially overcome immune resistance in prostate cancer. Prostate tumours are often characterized as ‘cold’ tumours due to their challenging tumour microenvironment, which hinders the delivery of drugs to cancer cells. Emerging developments in the form of bispecific antibodies, CAR T-cells, and antibody-drug conjugates offer promising prospects for infiltrating tumour cells. Ongoing trials in this domain hold significant promise, and the results are highly anticipated.
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