Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer Guideline Update

Dr. Katherine Virgo discusses the latest evidence-based guideline recommendation updates regarding initial management of metastatic prostate cancer based on the new clinical trial results comparing triplet therapies (the addition of darolutamide, abiraterone, or enzalutamide to docetaxel plus androgen deprivation therapy) to standard of care. Dr. Virgo also discusses cost of treatment options and ongoing research questions in this field. Read the full guideline, “‘Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update” at www.asco.org/genitourinary-cancer-guidelines. TRANSCRIPT This guideline, clinical tools, and resources are available at www.asco.org/genitourinary-cancer-guidelines. Read the full text of the guideline and review authors’ disclosures of potential conflicts of interest disclosures in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.23.00155.  Brittany Harvey: Hello and welcome to the ASCO Guidelines podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges, and advances in oncology. You can find all the shows, including this one, at asco.org/podcasts.   My name is Brittany Harvey, and today I am interviewing Dr. Katherine Virgo from Emory University, lead author on the ‘Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update’.   Thank you for being here, Dr. Virgo.  Dr. Katherine Virgo: Thank you.  Brittany Harvey: Before we discuss this guideline, I'd just like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO Conflict of Interest Policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Virgo, are available online with the publication of the guideline update in the Journal of Clinical Oncology, which is linked in the show notes.    So then, getting into the content of this update first, Dr. Virgo, what prompted this update to the initial management of noncastrate advanced, recurrent or metastatic prostate cancer guideline?  Dr. Katherine Virgo: The update is primarily driven by new clinical trial results comparing triplet therapies to standard of care. Triplet therapy here refers to the addition of darolutamide, abiraterone, or enzalutamide to docetaxel plus androgen deprivation therapy for patients with de novo metastatic noncastrate prostate cancer.  Brittany Harvey: Great. And then, based on this, what are the new and updated recommendations from the guideline panel?   Dr. Katherine Virgo: The first updated recommendation adds darolutamide to the list of treatment options as follows: docetaxel, abiraterone, enzalutamide, apalutamide or darolutamide, each when administered with androgen deprivation therapy, represent five separate standards of care for noncastrate metastatic prostate cancer, with the exception of the triplet therapies of docetaxel plus abiraterone plus ADT and docetaxel plus darolutamide plus ADT. The use of any of these agents in any other particular combination or in any particular series cannot yet be recommended.   The second updated recommendation states: for patients with metastatic noncastrate prostate cancer with high volume disease as defined per CHAARTED, who are candidates for treatment with chemotherapy but are unwilling or unable to receive triplet therapy, for example, due to insurance constraints, docetaxel plus ADT should be offered. We add some practical information here. Patients should be made aware that doublet therapy, docetaxel plus ADT, has inferior overall survival compared to triplet therapy, such as abiraterone and prednisone plus docetaxel plus ADT.   Then, I have a few recommendations here with respect to triplet therapy, and these are new. For patients with de novo metastatic noncastrate prostate cancer with high volume disease as defined per CHAARTED who are being offered ADT plus docetaxel chemotherapy, triplet therapy, abiraterone and prednisone plus ADT and docetaxel should be offered per the PEACE-1 trial. Abiraterone and prednisone plus ADT and docetaxel demonstrated significant overall survival and radiographic progression-free survival benefits compared to ADT and docetaxel alone for patients with high volume disease.   Again, we add some practical information. Overall survival data for patients with low volume de novo metastatic noncastrate prostate cancer from the PEACE-1 trial are still too immature to justify recommending abiraterone-based triplet therapy, in other words, abiraterone and prednisone plus ADT and docetaxel, for patients with low volume de novo metastatic noncastrate disease.   A second new recommendation, as opposed to a revised recommendation with respect to triplet therapy, is: for patients with de novo metastatic noncastrate prostate cancer who are being offered ADT plus docetaxel chemotherapy, triplet therapy, darolutamide plus ADT and docetaxel should be offered per the ARASENS trial. Compared to placebo plus ADT and docetaxel, darolutamide plus ADT and docetaxel demonstrated significant overall survival benefits, in addition to significantly longer times to castration-resistant prostate cancer, pain progression, first skeletal event, and initiation of subsequent systemic antineoplastic therapy.   The practical information offered here is that discussion with patients should include the cost of darolutamide treatment compared with other options, such as abiraterone. There was no change to the 2021 recommendation for enzalutamide other than to report long term results from the ENZAMET and ARCHES trials that was not available in 2021. We added similar practical information here with respect to discussing costs of enzalutamide treatment. Discussion with patients should include the cost of enzalutamide treatment compared with other options, such as abiraterone.  Brittany Harvey: Excellent. I appreciate you reviewing those new and updated recommendations from the expert panel along with that practical information.   So then, Dr. Virgo, what should clinicians know as they implement these updated recommendations? And also, in your view, how will these guideline recommendations affect patients with noncastrate metastatic prostate cancer?   Dr. Katherine Virgo: That's a good question. Clearly, cost is a factor for patients, and we felt it was important to emphasize this in the guideline update. In the data supplement to the guideline update, we included a table listing all the agents discussed in the update, as well as the associated pivotal trials, main outcomes, the control group, the cost per cycle of treatment, and the cost for the full treatment course. This should be particularly helpful to clinicians as they discuss treatment options with patients. We also thought it would be helpful to have a visual guide to treatment options that reflects the clinician's decision-making process more directly. So figure one is the result of a group effort to achieve that aim.  Brittany Harvey: Excellent. And there have been a lot of changes in this field that prompted this update, but what are the outstanding questions regarding triplet therapy in the treatment of patients with metastatic noncastrate prostate cancer?   Dr. Katherine Virgo: Well, the burning question is whether docetaxel is really still necessary in the treatment of patients with metastatic noncastrate prostate cancer. No phase III clinical trials have yet compared, for example, androgen deprivation therapy plus darolutamide or androgen deprivation therapy plus abiraterone versus androgen deprivation therapy plus docetaxel. Also improved overall survival for patients undergoing triplet therapy is largely confined at present to those with high volume disease. So for patients with low-volume disease, clinical trials as yet show no significant benefit of triplet therapy.  Brittany Harvey: Great. Well, then I guess we'll look forward to future trials to determine if that's still appropriate and look for future updates of this guideline.   So I want to thank you so much for your time developing and updating this guideline. And thank you for joining me today, Dr. Virgo.  Dr. Katherine Virgo: Thank you. I appreciate it.   Brittany Harvey:  And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/genitourinary-cancer-guidelines. You can also find many of our guidelines and interactive resources in the newly redesigned ASCO Guidelines app, available for free in the Apple App Store or the Google Play Store. 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