Assessing the ARANOTE Trial: Role of Darolutamide in Enhancing ADT for HSPC

A roundtable discussion, moderated by Andrew Laccetti, MD, MS, of Memorial Sloan Kettering Cancer Center, focused on the treatment landscape of metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC), including insights on the integration of recent research and clinical trials, how molecular subtyping affects treatment decisions, the future of care, and more. Dr. Laccetti was joined by Eleni Efstathiou, MD, PhD, of Houston Methodist Cancer Center; Ulka Vaishampayan, MD, of University of Michigan; and Michael Schweizer, MD, of Fred Hutchinson Cancer Center.

In the third part of this roundtable series, the panelists share their thoughts on the results of the ARANOTE trial and androgen deprivation therapy approaches to HSPC.

View the next segment of this roundtable series: SPLASH Trial Findings: Balancing Enthusiasm and Realities of PSMA Radiotheranostics

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Dr. Laccetti:
I want to move on to one of the next notable studies from the ESMO meeting, which is the ARANOTE trial. This was a phase III international study for men with hormone-sensitive prostate cancer that were newly diagnosed and treatment naive with the exception of ADT monotherapy for up to 90 days.

Men were randomized to receive either ADT monotherapy or in combination with darolutamide and the primary endpoint of RPFS was observed in this trial in addition to an early trend towards an overall survival advantage.

Although the data was immature, side effect profiles were as expected relative to other darolutamide-containing trials.

I think we’re all pleased to see data in this capacity because we view darolutamide as a very reasonable option amongst our other ARPIs, and to see it without chemotherapy in the HSPC setting with positive results opens up some options.

So again, I’ll open the question up to the group. What is everyone’s thoughts on the ARANOTE data?

Dr. Schweizer:
I mean, it’s not surprising. I think I would have been shocked if it wasn’t a positive study. We know from multiple phase III trials that adding an ARPI upfront to ADT benefits progression free survival, and I’m guessing we’re going to see an overall survival benefit too once the data is a little more mature.

Once it shows a substantial benefit, hopefully this leads to an approval and we won’t have any challenges in terms of getting darolutamide monotherapy for patients presenting with hormone-sensitive prostate cancer.

As it stands, the approval is based on the ARASENS trial, which looked at docetaxel with darolutamide and showed a benefit there compared to docetaxel with control.

I think depending on how insurers look at the situation, patients may be able to receive monotherapy, but many times they can’t. So this is going to make it a lot easier, and it’s good to have options.

Dr. Vaishampayan:
As we know from the other studies – LATITUDE, ARCHES, etcetera – you know we already knew that the addition of ARPI for metastatic hormone-sensitive disease is almost essential for a majority of the eligible patients, based on the improvement in PFS as well as overall survival.

So this adds another option to our different armamentarium of agents that we have now to consider adding to the initial ADT.

Dr. Efstathiou:
I’d like to add to your great comments and do a little bit of a flashback on when we were first listening to the data on darolutamide. I remember we were listening to presentations with regards to ARAMIS suggesting that there was a very favorable safety profile, and many of us thought that it couldn’t be true. Even though I had been involved in abiraterone, enzalutamide, and so forth, I had not been involved in trials with darolutamide.

Over time, however, we all started to use it and became more comfortable. I believe that ARANOTE was a coerced and required trial because we wanted to see it being able to be within the doublets and in the guideline.

ARASEN’s design was essentially mandated because through CHAARTED and STAMPEDE, we had the docetaxel in there, so it was designed after. There’s some criticism as to why the trial was allowed to do it versus an ADT alone, but it was done in countries where there was really no access to a doublet. Patients would probably be able to crossover once they reach that RPFS.

So all in all, we’re going to hear about one more trial coming from the US. It’s the single-arm ARASEC trial, and they think it’s going to give us more of an understanding within the guidelines to use it as a doublet.

One comment about the overall survival data – it’s too early. We all know that within the first 2 years, we unfortunately lose those patients, no matter what we treat them with. And that was only 25 months of median follow-up.

Dr. Laccetti:
Excellent points, and again, this study will hopefully afford another option for the management of hormone-sensitive disease. And again, it’s an embarrassment of riches; the adding of these extra agents creates more challenges in the clinic, but it does open opportunity for personalization, where we’re working with limited information.

A common theme of the meeting is the need for more biomarkers and predictors for which therapies are best, but having more options can help at the patient level.