Updated ASCO guidelines for non-castrate, recurrent, advanced, or metastatic prostate cancer focus on data from the PEACE-1, ARASENS, ENZAMET and ARCHES trials.

“The major reason for the update to the 2021 ASCO guidelines on the initial management of non-castrate, recurrent, advanced, or metastatic prostate cancer was newly released evidence from clinical trials of triplet therapy,” Katherine S. Virgo, PhD, MBA, notes. “The new recommendations were developed based on a literature review spanning June 2020 to August 2022 to identify any additional phase 3 randomized controlled trials of treatment options in metastatic, non-castrate, prostate cancer.”

The search criteria focused on research “central to the discussion of triplet therapy and trials,” according to the study results.

Clinical Trials: PEACE-1, ARASENS, ENZAMET & ARCHES

The guideline was published in the Journal of Clinical Oncology. “The major clinical findings pertained to the benefits of triplet therapy compared with doublet therapy for de novo metastatic non-castrate prostate cancer,” Dr. Virgo says.

The updates include both a description of the evidence type used for the recommendation as well as information about the strength of the recommendation. The main therapies discussed in the updates were docetaxel, abiraterone, enzalutamide, and darolutamide.

“The PEACE-1 trial found that abiraterone and prednisone plus ADT and docetaxel (triplet therapy) demonstrated significant overall survival and radiographic progression-free survival benefits compared with ADT and docetaxel alone for patients with high-volume de novo metastatic non-castrate prostate cancer,” Dr. Virgo explains. “The ARASENS trial found that, compared with placebo plus ADT and docetaxel, darolutamide plus ADT and docetaxel (triplet therapy) 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. Regarding the ENZAMET and ARCHES trials, there was no change to the 2021 recommendation for enzalutamide other than to report long-term results from these trials.”

The researchers also provide a flow chart for the initial management of non-castrate metastatic prostate cancer (Figure).

Practical Recommendations & Directions for Future Research

Some of the updates include practical recommendations, which are designed to “remind practicing clinicians about elements of treatment that are important to discuss with patients so that they fully understand the choices they are making,” Dr. Virgo says.

“For example, it is important that patients understand the higher cost of androgen receptor inhibitors compared with other less expensive options,” she continues. “Patients should be made aware that doublet therapy with docetaxel plus ADT has inferior overall survival compared with triplet therapy, such as abiraterone and prednisone plus docetaxel plus ADT. Docetaxel is also associated with somewhat greater toxicity than androgen-targeted therapies, though the treatment course is relatively short (limited to six cycles), much less costly, and generally covered by insurance, thereby reducing financial toxicity.”

The updated guidelines also provide directions for future research.

“Is docetaxel still necessary in metastatic non-castrate prostate cancer? No phase 3 clinical trials have yet compared, for example, ADT plus darolutamide or ADT plus abiraterone versus ADT plus docetaxel,” Dr. Virgo says. “This is an as-yet unanswered question and will likely be the focus of the next guideline update, once randomized clinical trial data become available. Another unanswered question is how to treat patients with low-volume de novo metastatic non-castrate prostate cancer.”