ASCO publishes guideline update for initial management of noncastrate advanced prostate cancer

The American Society of Clinical Oncology (ASCO) has published an update to its guideline for initial hormonal management of noncastrate advanced, recurrent, or metastatic prostate cancer.¹

The latest guideline, which was published online in the Journal of Clinical Oncology, was developed by a multidisciplinary expert panel. The recommendations were made based on a systemic review of 4 clinical practice guidelines, 1 endorsement of a clinical practice guideline, 19 systematic reviews, 47 phase 3 randomized controlled trials, 9 cohort studies, and 2 review papers.

These are the recommendations established by the expert panel:

• There are 4 standards of care for the initial treatment of noncastrate metastatic prostate cancer, consisting of androgen deprivation therapy (ADT) combined with either docetaxel, abiraterone acetate (Zytiga), enzalutamide (Xtandi), or apalutamide (Erleada). The treatments are indicated both as initial frontline treatment and in previously treated patients without disease progression. ASCO has no specific recommendation regarding sequencing or combining these 4 agents.

• Rather than single-agent castration therapy, physicians “should consider” the combination regimen of ADT plus abiraterone and prednisolone in patients with noncastrate locally advanced nonmetastatic disease previously treated with radiotherapy.

• In men presenting with noncastrate locally advanced nonmetastatic prostate cancer, immediate ADT is an option in men with no prior local therapy who are ineligible for or unwilling to receive radiotherapy.

• Patients with high-risk biochemically recurrent nonmetastatic disease “may be offered” intermittent ADT.

• Active surveillance is an option for patients with biochemically recurrent nonmetastatic prostate cancer that is low risk.

• Across all noncastrate settings, ASCO does not currently recommend using either micronized abiraterone acetate or the approach of taking a reduced abiraterone dose with a low-fat breakfast.

Of the newer agents recommended for initial management, abiraterone was the first to be approved by the FDA. In February 2018, the FDA approved abiraterone for use in combination with prednisone for patients with metastatic high-risk castration-sensitive prostate cancer. The approval was supported by the phase 3 LATITUDE trial, in which there was a 38% reduction in the risk of death with the addition of abiraterone acetate and prednisone to ADT compared with ADT alone.²

Next, in September 2019, the FDA approved apalutamide for the treatment of patients with metastatic castration-sensitive prostate cancer. The approval was based on the phase 3 TITAN trial which showed that apalutamide plus ADT led to a 33% reduction in the risk of death compared with placebo plus ADT.³

The third of the newer agents approved in this setting was enzalutamide, which the FDA approved in December 2019 for the treatment of patients with metastatic castration-sensitive prostate cancer. The approval was based in part on the phase 3 ARCHES trial in which there was a 61% reduction in the risk of radiographic progression or death with enzalutamide plus ADT compared with placebo plus ADT.⁴

The complete details and supporting data for this ASCO guideline are available in the full publication at https://bit.ly/3t5Ve6P.

References

1. Virgo KS, Rumble RB, de Wit R, et al. Initial management of noncastrate advanced, recurrent, or metastatic prostate cancer: ASCO guideline update [published online January 26, 2021]. J Clin Oncol. doi: 10.1200/JCO.20.03256

2. Fizazi K, Tran N, Fein LE, et al. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017;377:352-360. doi: 10.1056/NEJMoa1704174

3. Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for metastatic, castration-sensitive prostate cancer [published online May 31, 2019]. N Engl J Med. 2019;381(1):13-24. doi: 10.1056/NEJMoa1903307

4. Xtandi (Enzalutamide) approved by U.S. FDA for the treatment of metastatic castration-sensitive prostate cancer [news release]. Pfizer. Published December 16, 2019. https://bit.ly/2tpujIV. Accessed January 28, 2021.