Highlights on prostate & penile cancer

Prof Dr Piet Dirix, a radiation oncologist at the Iridium Network in Antwerp, highlights the most interesting presentations from the oral abstract session on prostate, testicular, and penile cancer.

The HERCULES trial, a phase 2 study conducted across 11 centres in Brazil, evaluated the efficacy of first-line cisplatin-based chemotherapy combined with pembrolizumab in patients with penile cancer. Eligible participants had metastatic or locally advanced disease, specifically at stage T4N or TN3. The primary endpoint, confirmed ORR, reached 40%, suggesting a potential benefit of immunotherapy in this heavily burdened patient population. High TMB and a high prevalence of HPV-16 positivity were identified as biomarkers.

A second trial on immunotherapy, the NEPTUNES trial, was presented for mPC. This is one of the first trials to demonstrate a positive response to immunotherapy, attributed to careful patient selection. The trial included patients with highly immunogenic subtypes, such as those with DNA repair deficiency, mismatch repair deficiency, or high TILs. A combination of ipilimumab and nivolumab was administered in two different doses. The primary endpoint, ORR, ranged from 30% to nearly 40% for one specific combination. This trial suggests that immunotherapy may be effective for prostate cancer if the right patients are selected.

Two abstracts were presented showcasing new drugs for mCRPC. The first compound, JNJ-6420, is an antibody targeting hK2, labelled with actinium, an alpha-emitting radioligand. This first-in-human trial investigated dosage and safety. Higher doses were associated with significant toxicity, including ILD and thrombocytopenia. However, at the correct dose, the drug was well-tolerated and demonstrated a promising PSA response rate. The second drug, ARV-766, a PROTAC androgen receptor degrader, is further along in development, having been tested in a phase 1/2 trial. The correct dose has been established, and PSA50 response rates of 43% were demonstrated. Compared to JNJ-6420, ARV-766 was very well-tolerated and showed minimal toxicity.

About 10-15% of patients with mCRPC will develop neuroendocrine differentiation. Tarlatamab induces T-cell-mediated tumour lysis in DLL3-expressing tumour cells. In this phase 1 trial, despite a limited number of participants, a relatively promising ORR of around 10-15% was observed. Given the difficulty in treating these tumour types, tarlatamab could become a viable treatment option.

The last study examined PSMA-PET as a predictor of overall survival using the PROMISE database, including nearly 1,600 prostate cancer patients at various stages, from localized to advanced disease. Researchers assessed tumour load, presence of lymph nodes, presence of metastasis, and the median SUV. Based on these four parameters, their mathematical prediction of OS outperformed every comparative database available, including STARCAP for localized disease, EAU risk categories for biochemical recurrence, and the NCCN risk groups for all disease stages. The findings need confirmation in a prospective trial but underscore the immense power of PSMA-PET in prostate cancer.