Prostate cancer (PC) is the second most common cancer and the fifth leading cause of cancer mortality in men, worldwide. Genomic analysis identified alterations in DNA damage repair (DDR) pathways, in up to 30% of metastatic castration-resistant prostate cancer (mCRPC). Homologous recombination repair (HRR) mutations in BRCA1/2 emerged as a relevant biomarker in PC, linked to aggressive behavior, unfavorable outcomes and notable responses to poly-ADP ribose polymerase inhibitors (PARPi). While PARPi efficacy in BRCA-mutated mCRPC is well established, their role in earlier disease stages is currently under investigation. This non-systematic narrative review aims to summarize current evidence on PARPi in PC, outlining approved indications, ongoing clinical trials, and emerging therapeutic strategies across different disease settings.

Background: Immune checkpoint inhibitor–tyrosine kinase inhibitor combinations represent a standard first-line option for metastatic renal cell carcinoma (mRCC). However, patients enrolled in pivotal trials often differ from those treated in routine practice. We report real-world outcomes of pembrolizumab plus axitinib within the Campania Oncology Network. Methods: We conducted a multicenter retrospective study including consecutive treatment-naïve mRCC patients who received first-line pembrolizumab plus axitinib between January 2021 and November 2023 across eight regional centers. The primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR) and safety. Results: A total of 117 patients were included. IMDC risk was favorable in 19.6%, intermediate/poor in 65%, and unknown in 15.4%. Median age was 59 years, and 53.8% had ECOG performance status ≥ 1. Clear-cell histology accounted for 87.2% of cases; brain metastases were present in 36%. After a median follow-up of 12.8 months, median PFS was 15.1 months (95% CI 9.6–NR), and median OS was not reached. ORR was 27.3%, with a disease control rate of 79.5%; patients with non-clear-cell histology showed an ORR of 41.7%. Disease progression was the main cause of treatment discontinuation (49%), while adverse events (AEs) led to discontinuation in 6% of cases. Grade ≥3 AEs occurred in 14% of patients. Most toxicities were grade 1–2, including diarrhea (23.9%), asthenia (18%), hypothyroidism (12.8%), and hypertension (9.4%). Grade 1–2 AEs were significantly more frequent in females compared with males (57.6% vs. 35.7%, p = 0.05). Conclusions: In this consecutive regional cohort, pembrolizumab plus axitinib showed clinically relevant disease control, although ORR was lower than in pivotal trials. Performance status emerged as a key prognostic factor. Real-world data from oncology networks may support personalized first-line treatment decisions in mRCC.