mCRPC in focus
Transcript: Precision medicine for mCRPC
Dr Alexander Chehrazi-Raffle
Interview recorded June 2024. All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
Yeah, so precision medicine has been a mainstay of mCRPC since the PROfound study established olaparib as an efficacious option for patients who harbour HRR mutations in 2020. So over the past four years, we've seen guidelines adapt to this changing landscape and it currently, NCCN recommends germline testing for all patients with high-risk localised disease and somatic testing for all patients with metastatic disease. In addition to ARV-766 with their ligand binding domain mutations, there's several new biomarker-driven treatment approaches that are on the horizon.
One that was presented at ASCO is NEPTUNES and it was reporting nivolumab, ipilimumab in a biomarker-selected population that includes defective DNA repair, mismatch repair, and inflammatory infiltrate by IHC. So the primary endpoint of this study was a composite of radiologic response, PSA 50 response, and conversion to circulating tumour cells at nine weeks. Across 36 patients, response rate was an encouraging 40% with several durable responses, suggesting that immune checkpoint inhibit may in fact be an effective option for properly-selected patients. Another study presented this year was by Dr. Yue Chen and it leveraged a commercial database of Caris of prostate cancer tumours from primary and distant metastases to develop transcriptomic signatures, so downstream of the DNA.
They found that prostate cancer tumours can further be characterised by androgen receptor signalling, neuroendocrine receptor signalling, and co-occurring molecular alterations. These signatures are planned to be incorporated into the PREDICT trial, which will sign patients with actionable alterations to targeted therapies and compare that to non-targeted standard of care options. Suffice it to say that precision medicine has arrived for metastatic prostate cancer and there's much more to come on the horizon, which is a big win for patients as there are more personalised therapies and they can offer superior efficacy in many cases compared to mutational-agnostic options.
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