Mutations associated with DNA repair are found in about one‐quarter of prostate cancers, with BRCA2 being the most frequently affected genes and with BRCA1/2 mutations occurring both at the somatic and germline levels. Metastatic castration‐resistant prostate cancer (mCRPC) with BRCA1/2 mutations is preferentially sensitive to poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitors via a synthetic lethal mechanism. In addition, emerging evidence suggests that patients with BRCA2‐related CRPC responded to platinum‐based chemotherapy at a high rate. In this case report, Miyazawa et al. reported two cases of mCRPC with BRCA mutations that responded well to cisplatin followed by olaparib. 1 Recently, Slootbeek et al. reported four cases of mCRPC with BRCA2 mutations that responded to both platinum‐based chemotherapy and subsequent PARP inhibitors. 2 Mota et al. evaluated the efficacy of platinum‐based chemotherapy after PARP inhibitor treatment in mCRPC patients with mutations in DNA damage repair genes. Of the 6 patients with BRCA1/2 mutations, 3/5 evaluable patients had a radiological partial response or stable disease and 2/5 had a PSA50 response. 3 These results provide insights into cross‐resistance between PARP inhibitors and platinum chemotherapy in patients with BRCA‐mutated mCRPC.
The two cases presented in this case report were treatment‐induced neuroendocrine prostate cancer (NEPC), which is generally considered to have a poor prognosis. 1 NEPC is an aggressive variant of prostate cancer, which may occur de novo or in patients who have previously received hormone therapy. Genomic features of NEPC are associated with reduced AR signaling and concurrent loss of RB1 and TP53. 4 Platinum‐based chemotherapy regimens, such as the combination of cisplatin and etoposide, are widely used in NEPC patients. In men with NEPC who have responded to platinum‐based chemotherapy, genetic testing to detect PARP inhibitor candidates may be worth considering.
Funding information
This research was supported by the Japan Society for the Promotion of Science KAKENHI (grant number 22K09447).
Conflict of interest
KH has received grants/research supports from Astellas Pharma Inc.
References
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