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mCRPC in focus
Transcript: CHAARTED-2 and A-DREAM
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, there were two cooperative group studies that stood out to me at ASCO this year. CHAARTED2 and A-DREAM. So CHAARTED2 is an ECOG-ACRIN randomised phase 2 study of patients with high volume mCRPC, who previously progressed on docetaxel in the metastatic hormone sensitive setting. In this study, 210 patients were randomised one-to-one to receive cabazitaxel plus abiraterone versus abiraterone alone. The primary endpoint was rPFS and at a median followup of 47 months, median rPFS of cabazitaxel plus abiraterone was 15 months compared to 10 months with abiraterone alone equating to a hazard ratio of 0.73, which was significant. Subgroups that derive the most benefit were patients with a visceral metastases, time to castration-resistance of less than 12 months, age less than 65, and ECOG, zero. However, no survival difference was observed with a hazard issue of 0.9, but it was underpowered to look at overall survival.
So to me, the big takeaway from CHAARTED2 is that ARPI plus cabazitaxel is something worth exploring as an alternative to ARPI plus docetaxel for high-volume metastatic hormone sensitive prostate cancer which is the current FDA-approved combination per ARASENS and PEACE-1. Why I say that is because cabazitaxel, unlike docetaxel, doesn't come with this sort of dose limiting toxicity that prevents us from using it beyond about six cycles. So it could offer a bit more durability of response when used in triplet therapy in the hormone sensitive setting.
The other cooperative group that caught my attention was a trials in progress poster for A-DREAM which is being run through the Alliance Consortium. This study's evaluating systemic therapy interruption of ADT plus ARPI after about 18 to 24 months in patients who achieve a PSA of less than 0.2. The study enrolled 79 patients and the primary endpoint is a proportion of treatment-free patients with eugonadal testosterone 18 months after interruption. Triggers for reinitiation of therapy are PSA greater than five, radiographic change, or prostate cancer related syndromes. If positive, this study would have powerful implications if patients with favourable responses could potentially be taken off of systemic therapy, which would not only improve their quality of life, their toxicities, but also systematic financial burdens that come along with lifelong therapy of these treatments.
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