Navigating ARANOTE Trial Findings and Insurance for Prostate Cancer

Darolutamide (Nubeqa) is an androgen receptor inhibitor that, when combined with androgen-deprivation therapy (ADT), has demonstrated significant efficacy in treating metastatic hormone-sensitive prostate cancer (mHSPC). Tian Zhang, MD, MHS, an associate professor and director of clinical research within the Division of Hematology and Oncology in the Department of Internal Medicine, and the associate director of clinical research in the Simmons Comprehensive Cancer Center at UT Southwestern Medical Center, reviewed the results of the phase 3 ARANOTE trial (NCT04736199), during a live Community Case Forum in Frisco, Texas. Zhang also detailed the practical challenges of insurance coverage and her approach for discussing the various treatment options with newly diagnosed patients.

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This article is part 2 of a 2-part series from a Case-Based Roundtable event.

Targeted Oncology: Please discuss the design of the phase 3 ARANOTE trial for darolutamide and ADT vs ADT with placebo.

Tian Zhang, MD, MHS: This [trial enrolled] patients with metastatic hormone sensitive prostate cancer. If they had received hormone deprivation less than 12 weeks before they were randomly assigned, they could not have had prior second-generation AR-targeted therapy. They had good performance status and good organ function. They were stratified if they have visceral metastases or prior local therapy, if they had metachronous disease vs synchronous. The primary end point was radiographic progression-free survival [rPFS], and overall survival [OS] was a secondary end point. They also looked at time to start of second subsequent treatments, time to metastatic castration resistance, time to prostate-specific antigen [PSA] progression, rates of undetectable PSA, time to pain progression, and also safety.¹

It was a 2:1 randomization, so more people received the doublet than received the placebo. Of note, there were a high number of Asian patients on this global trial, as well as about a 10% black population. About a quarter of these patients were recruited from Latin America, and about 30% were recruited in Asia. It was not a United States trial in that we had multiple standards of care in the United States, and so they went ex-United States for this particular trial. Most of the baseline characteristics mirror what we usually see. Of note, about 70% of patients had de novo metastatic disease and 12% had visceral metastases for those stratification markers.^1,2

What was the efficacy data reported at the 2024 European Society for Medical Oncology Congress (ESMO)?

The primary end point was presented at ESMO in 2024 [and it showed that] darolutamide with ADT improved that median PFS at 2 years. The 2-year PFS rate was 70% compared with ADT with placebo at 52%. This was statistically significant with an HR of 0.54.²

If we look at it by subgroup, most of these predefined subgroups favored patients treated with ADT and darolutamide. Some of the confidence intervals did cross 1.0 because of low numbers [in the] black patient population, for example, the visceral metastases category, or over 85-years-old category, but they did enroll people in all of those categories.

For secondary efficacy, the OS end point did cross 1.00. Time to metastatic castration resistant disease favored ADT with darolutamide, time to PSA progression, pain progression, and time to initiation of subsequent treatment all favored patients treated with ADT and darolutamide.

Most notably, time to metastatic castration resistance as well as time to PSA progression—which are similar concepts— had HRs in the 0.3 to 0.4 range. Time to pain progression is much more subjective; there was less of a split between the 2 Kaplan-Meier curves. Sixty-two percent of patients on the doublet had a PSA that was undetectable, less than 0.2 ng/mL during treatment, whereas only 18% of those treated with ADT and placebo achieved PSA undetectable.

How do you discuss insurance coverage and starting treatments such as this with patients?

There's better co-pay assistance if they're on commercial insurance. Medicare, at least this year, has a cap of about $2000 out of pocket, so it's a little bit better than previously for the whole year. Usually what we're seeing is somewhere around $500 to $800 for each co-pay, and then 3 months in, they're done. But I don't know what the current changes in policies are going to affect for future costs. That's an ongoing issue.

When I talk about these [regimens] in my practice, I say there are 4 approved options, and none of them have not been compared head-to-head for efficacy. So I at least have them hear the drug names, we give them printouts, and then we say we'll start with one option and then usually [because of] adverse events, they're opting for darolutamide. But then we say if we're unable to get this because of the co-pay costs or some other reason, don't be surprised if we then need to go to apalutamide [Erleada], enzalutamide [Xtandi], or even abiraterone [Zytiga] because that's the only generic option. So at least they're hearing it. Especially for synchronous metastatic disease, it's a long conversation; you're talking about genomic testing, could their kids have it, and then you're talking about all of the options, and getting them started on ADT, sometimes chemotherapy.

I layer that in, so in the first month, we talk about their new diagnosis, starting on ADT, and we get them started. A month later, we then talk about that oral combination, whether they meet all the criteria. Usually, we're getting a bone scan in that month to decide if it is high-volume disease, so then we're talking about whether they should do the triplet vs doublet. That's my layered approach, otherwise patients are overwhelmed. You tell them they need ADT, docetaxel, and an oral agent all at the same time, it's a lot to take in.

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DISCLOSURES: Zhang has previously reported having stock and leadership roles in Capio Biosciences, Archimmune Therapeutics, and Nanorobotics. They have served as a consultant or advisor for Exelixis, Pfizer, Bristol Myers Squibb, Seagen, Eisai, Aravive, Bayer, Lilly, Aveo, Merck, Sanofi/Aventis, Novartis, Gilead Sciences, EMD Serono, AstraZeneca, Loxo/Lilly, Xencor, and Johnson & Johnson/Janssen. They have also received honoraria from MJH Life Sciences, Aptitude Health, Curio Science, Peerview, Clinical Care Options, Mashup Media, and Dava Oncology. They have received travel, accommodation, or expenses from Bayer. They also have relationships with ASCO, Kidney Cancer Association KidneyCan, Myrovlytis Trust, and Winn Foundation.

REFERENCES:

1. Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. J Clin Oncol. 2024;42(36):4271-4281. doi:10.1200/JCO-24-01798

2. Saad F, Vjaters E, Shore ND, et al. LBA68 Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Ann Oncol. 2024;35(suppl 2):S1257-S1258