Advancing Treatment for High-Risk Biochemical Recurrence Prostate Cancer: The ARASTEP Trial - Alexander Chehrazi-Raffle

June 12, 2024

Zach Klaassen discusses the ARASTEP trial with Alex Chehrazi-Raffle. The trial focuses on patients with high-risk biochemical recurrence of prostate cancer, specifically those who show positive results on PSMA PET scans but are negative on conventional imaging. Dr. Chehrazi-Raffle explains that ARASTEP, a randomized phase 3 study, aims to evaluate the efficacy of combining androgen deprivation therapy (ADT) with darolutamide for 24 months versus ADT alone. The primary endpoint is the detection of distant metastasis on PSMA PET CT, with secondary endpoints including overall survival and quality of life. This trial uniquely integrates PSMA PET imaging every three months to monitor disease progression. Currently, ARASTEP is enrolling patients, with plans to include 750 participants globally.


Alexander Chehrazi-Raffle, MD, Oncologist, Assistant Professor, Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA

Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Well Star MCG, Georgia Cancer Center, Augusta, GA

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Zach Klaassen: Hi, my name is Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are live in Chicago at ASCO 2024, and I'm delighted to be joined by Dr. Alex Chehrazi-Raffle, a medical oncologist at City of Hope. Alex, thanks so much for joining us today.

Alexander Chehrazi-Raffle: Thanks for the invitation. Pleasure to be here.

Zach Klaassen: We're going to talk about a really cool trial that you're presenting in the "trials in progress" section at ASCO, ARASTEP. Just by way of background, tell us a little bit about the high-risk biochemical recurrence disease state and the need for high-quality data, particularly in the PSMA PET era.

Alexander Chehrazi-Raffle: Yeah, absolutely. Biochemical recurrence occurs in approximately 50% of patients who undergo definitive radiation and 20 to 30% of patients who undergo prostatectomy. Within that subgroup, you have quite a variety of patients. When we see the doubling time go to less than 12 or less than nine months, it's really predictive for patients who are going to become metastatic. In recent years, there have been several studies looking at this space to see if escalating therapy might improve patient outcomes. Fortunately, thanks to EMBARK, which came out last year, we saw that it does with enzalutamide for nine months in combination with Lupron or as monotherapy. In this study, it's a little different because we're harnessing a new biomarker, PSMA PET CT, one that's readily used in the community and clinical practice, to see if that defines an even higher-risk subpopulation.

Zach Klaassen: Absolutely, and we're definitely going to get into the trial design. But as a second question regarding background, we've known about darolutamide for a long time. Give us a high-level view of where we're using darolutamide already in the clinic today.

Alexander Chehrazi-Raffle: Yeah, darolutamide, as you point out, is a medication we've known for several years now that improves outcomes in the metastatic hormone-sensitive prostate cancer population. We saw that with ARASENS, in which it was given with docetaxel and ADT, and also in the non-metastatic castration-resistant prostate cancer setting, where ARAMIS showed that there was a survival advantage there as well, compared to ADT monotherapy. We know it's a great drug and it's tolerated very well by patients. It's one of the reasons that practitioners tend to turn to it when faced with the decision of choosing between it and others in that same sort of class.

Zach Klaassen: Talk about the trial design for ARASTEP, and maybe just walk us through specifically that PSMA PET component, which is a little bit different from the EMBARK trial.

Alexander Chehrazi-Raffle: Yeah, exactly. ARASTEP is a randomized phase 3 placebo-controlled global trial, and it's evaluating ADT for 24 months with or without darolutamide. In this study, one of the key components is that it's in a PSMA PET CT-positive, conventional imaging-negative patient population. In other words, we're seeing something on the PSMA PET, but absolutely nothing on conventional imaging. Why that's important is because we're going to be, for the first time, really seeing how that fares as an endpoint, with the primary endpoint being distant PSMA PET CT metastasis.

Zach Klaassen: I see. That's great. Basically, we're taking high-risk patients, conventional imaging negative, who have to be PSMA PET positive, and then seeing the resolution of those PSMA lesions after therapy.

Alexander Chehrazi-Raffle: Exactly. The other key component there is a PSA doubling time of less than 12 months.

Zach Klaassen: Are there specific time points when PSMA PET is being done in that two years of treatment, or is it just after the two years or if PSA is going up? What's sort of your imaging follow-up once they start treatment?

Alexander Chehrazi-Raffle: Imaging is done every three months, and it's a combination of both PSMA PET CT and conventional imaging.

Zach Klaassen: Excellent.

Alexander Chehrazi-Raffle: Yeah.

Zach Klaassen: You mentioned some of the outcomes already. The primary outcome is PSMA PET metastasis. What sort of secondary endpoints are you guys looking at as well?

Alexander Chehrazi-Raffle: We're looking at metastasis based on conventional imaging. We're looking at overall survival. We're also looking at quality of life metrics, which can be very important for patients and seeing how they fare.

Zach Klaassen: That's great.

Alexander Chehrazi-Raffle: Yeah.

Zach Klaassen: What's the status of ARASTEP? Are we getting close to the data? How's enrollment going? How many sites? How many patients?

Alexander Chehrazi-Raffle: Yeah. We are moving along nicely. We have 46 patients on the study as of April, and it's picking up pretty robustly.

Zach Klaassen: Great.

Alexander Chehrazi-Raffle: We're planning for 750.

Zach Klaassen: That's great. This is global, you mentioned. How many countries are we looking at for this study?

Alexander Chehrazi-Raffle: We're looking at in the twenties, I believe 23. Currently, we're only open in the US. We're in the process of launching elsewhere as well.

Zach Klaassen: Perfect. It's always a great discussion with you. Any take-home points for our listeners today?

Alexander Chehrazi-Raffle: Yeah, I think the take-home here is that this is a very high-risk population. We're seeing disease on this sort of new imaging modality that's allowing us to detect disease before it evolves onto conventional imaging. Using that in clinical practice is going to require us, in the context of phase 3 studies like this, to really define its role, rather than committing these patients to lifelong therapy.

Zach Klaassen: Right, exactly. Thanks so much for your time and expertise today, Alex. Great discussion on ARASTEP.

Alexander Chehrazi-Raffle: Yeah, thanks for the invitation.

Zach Klaassen: Thanks.