Michael J. Morris, MD
Matthew I. Milowsky, MD
As reported in the Journal of Clinical Oncology by Michael J. Morris, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medicine, and colleagues, ASCO has released a clinical practice guideline on optimizing anticancer therapy in men with metastatic non-castrate prostate cancer.1 To develop the guideline, an expert panel performed a systematic literature review for fully published English-language reports of phase III randomized controlled trials published from 2015 through October 2017, rigorously conducted systematic reviews, and meta-analyses. The panel was co-chaired by Dr. Morris and Matthew I. Milowsky, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill.
The guideline addresses the use of abiraterone (Yonsa, Zytiga) or docetaxel with androgen-deprivation therapy for metastatic prostate cancer that has not been treated, or has been minimally treated, with testosterone-lowering agents. The panel considered the evidence of three studies assessing overall survival with androgen-deprivation therapy alone vs androgen-deprivation therapy plus docetaxel (GETUG-AFU 15, STAMPEDE, and CHAARTED) and two assessing androgen-deprivation therapy alone vs androgen-deprivation therapy plus abiraterone (LATITUDE and STAMPEDE). The results of STAMPEDE (hazard ratio [HR] = 0.78, 95% confidence interval [CI] = 0.66–0.93) and CHAARTED (HR = 0.73, 95% CI = 0.59–0.89) favored the addition of docetaxel to androgen-deprivation therapy, whereas GETUG-AFU 15 was a negative trial. Both LATITUDE (HR = 0.62, 95% CI = 0.51–0.76) and STAMPEDE (HR = 0.63, 95% CI = 0.52–0.76) favored the addition of abiraterone (with prednisone or prednisolone) to androgen-deprivation therapy.
Key recommendations are reproduced/summarized here. The type of recommendation, evidence quality, and strength of recommendation are shown in parentheses.
Docetaxel and abiraterone are two separate standards of care for metastatic non-castrate prostate cancer. The use of both standards in combination or in series has not been assessed and therefore cannot be recommended (Type: evidence based, benefits/harms ratio unknown; Evidence quality: no evidence available; Strength of recommendation: strong).
Androgen-Deprivation Therapy Plus Docetaxel
For men with metastatic non-castrate prostate cancer with high-volume disease per CHAARTED who are candidates for treatment with chemotherapy, the addition of docetaxel to androgen-deprivation therapy should be offered (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong for patients with high-volume disease as per CHAARTED).
For patients with low-volume disease per CHAARTED who are candidates for chemotherapy, docetaxel plus androgen-deprivation therapy may be offered (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: moderate for patients with low-volume disease as per CHAARTED).
The appropriate regimen of docetaxel is 6 doses administered every 3 weeks at 75 mg/m2 either alone (per CHAARTED) or with prednisolone (per STAMPEDE; Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong).
Androgen-Deprivation Therapy Plus Abiraterone
For men with high-risk de novo metastatic non-castrate prostate cancer, the addition of abiraterone to androgen-deprivation therapy should be offered per LATITUDE (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong for patients with high-risk disease per LATITUDE).
For men with lower-risk de novo metastatic non-castrate prostate cancer, abiraterone may be offered per STAMPEDE (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: moderate for patients with lower-risk disease per STAMPEDE).
The appropriate regimen is abiraterone at 1,000 mg with either prednisolone or prednisone at 5 mg once daily until treatment(s) for metastatic castration-resistant prostate cancer are initiated (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong).
The strongest evidence of benefit for docetaxel is for those men who were diagnosed with de novo metastatic disease or high-volume disease per CHAARTED (defined as four or more bone metastases, one or more of which is outside the spine or pelvis, and/or the presence of any visceral disease). The criteria are agnostic to the presence or absence of nodal disease.
Men who do not fit into these categories may be offered docetaxel; however, the strength of the evidence to support an overall survival benefit is less compelling for men who do not have de novo metastatic disease and/or who do not meet the high-volume disease criteria. A subset analysis of CHAARTED did not demonstrate a survival benefit for low-volume disease, and the GETUG-AFU 15 trial was negative.
LATITUDE examined the benefits of abiraterone acetate in newly diagnosed men with metastatic non-castrate disease defined by high-risk factors associated with a poor prognosis including at least two of the following high-risk factors: a Gleason score ≥ 8, at least three bone lesions, and presence of measurable visceral disease. STAMPEDE did not include a high-risk definition.
The addition of either docetaxel or abiraterone to androgen-deprivation therapy in men with newly diagnosed metastatic prostate cancer offers a survival benefit compared with the use of androgen-deprivation therapy alone. The strongest evidence of benefit with docetaxel is in men with de novo metastatic high-volume disease, whereas the data in other patients with metastatic disease are less clear. LATITUDE and STAMPEDE are mutually supportive for treating high-risk disease with androgen-deprivation therapy and abiraterone, with STAMPEDE alone furnishing evidence that includes men with lower-risk disease.
In the absence of randomized data comparing the addition of docetaxel vs abiraterone to androgen-deprivation therapy in men with metastatic non-castrate disease, additional variables including patient comorbidities, toxicity, quality-of-life issues, drug availability, and cost will ultimately need to be taken into consideration.
Additional information is available at www.asco.org/genitourinary-cancer-guidelines. ■
DISCLOSURE: For full disclosures of the panel authors, visit www.jco.ascopubs.org.
1. Morris MJ, Rumble RB, Basch E, et al: Optimizing anticancer therapy in metastatic non-castrate prostate cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 36:1521-1539, 2018.
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