Androgen-Targeting Combos Show Promise in Prostate Cancer

Abiraterone (Zytiga) added to standard of care treatments significantly improved survival outcomes in patients with high-risk prostate cancer or de novo metastatic castration-sensitive disease, results from two randomized trials showed.

In STAMPEDE, abiraterone acetate plus prednisolone (AAP) and androgen deprivation therapy (ADT) with or without enzalutamide (Xtandi) improved metastasis-free and overall survival in men with high-risk prostate cancer over ADT alone, reported Gerhardt Attard, MD, PhD, of University College London.

In PEACE-1, adding abiraterone plus prednisone to standard of care (ADT and docetaxel with or without radiotherapy) improved radiographic progression-free survival (rPFS) and overall survival in men with de novo metastatic castration-sensitive prostate cancer, according to Karim Fizazi, MD, PhD, of Institut Gustave Roussy in Villejuif, France.

Findings from the trials were presented at the virtual European Society for Medical Oncology meeting.

STAMPEDE

Over 6 years, 82% of men treated with 2 years of AAP plus ADT remained free of metastases compared with 69% of men who received ADT alone (HR 0.53, 95% CI 0.44-0.64), a difference that was highly statistically significant, said Attard.

Addition of AAP also improved overall survival, with 6-year rates of 86% versus 77%, respectively (HR 0.60, 95% CI 0.48-0.73).

Treatment effects for ADT plus AAP were consistent with (HR 0.53, 95% CI 0.39-0.71) or without (HR 0.54, 95% CI 0.43-0.68) enzalutamide.

“The STAMPEDE report is truly practice changing. This addresses an unmet need of treating high-risk prostate cancer patients after 10 years of stagnant standard of care. These are positive outcomes that are clinically meaningful,” commented Eleni Efstathiou, MD, PhD, of Houston Methodist Cancer Center in Texas.

Approximately 20% of localized prostate cancers are high risk at diagnosis and account for the majority of relapses and subsequent deaths in this population, Attard noted. ADT combined with local radiotherapy to the prostate and pelvis improves survival. Adding treatments such as docetaxel has been shown to prolong time to relapse.

STAMPEDE included 1,974 patients from 113 sites in the U.K. and Switzerland; 914 patients were randomized to receive ADT or ADT plus AAP and 1,060 patients were randomized to ADT or ADT plus AAP and enzalutamide. Baseline characteristics were well-balanced, with a median age of 68 and a median prostate-specific antigen level of 34 ng/mL. Total median follow-up was 72 months.

Enzalutamide did not improve efficacy and increased adverse events, Attard said.

“Based on these results, all men with high-risk non-metastatic prostate cancer should be considered for 2 years of abiraterone,” Attard said. “This will involve more hospital visits during this period to manage administration of the drug, but by reducing subsequent relapse, may reduce the overall burden for both patients and health services.”

PEACE-1

PEACE-1 was a phase III trial with a 2×2 factorial design that included 1,173 patients with de novo metastatic castration-sensitive prostate cancer.

Median rPFS was 4.5 years for patients who received abiraterone plus prednisone and standard of care compared with 2 years for patients who received standard of care alone (HR 0.50, 95% CI 0.40-0.62).

Median overall survival also improved with the addition of abiraterone (HR 0.75, 95% CI 0.59-0.95).

“PEACE-1 is the first trial to establish that triplet treatment should be offered to these men, especially those with the most aggressive cancers,” Fizazi said. “Moreover, additional side effects with the triplet combination were mostly mild, with very few severe side effects.”

For men with high-burden metastatic prostate cancer, the triplet treatment provided 2.5 additional years without cancer progression and approximately 18 additional months of life, Fizazi pointed out. “For the first time, these men can expect to live more than 5 years, whereas before 2015 their median survival was less than 3 years. By 2022 all three treatments will be generic drugs, which should improve access for patients worldwide,” he added.

More follow-up is required in men with low-burden metastatic prostate cancer to accurately assess survival, Fizazi noted. “Triplet systemic treatment clearly postponed cancer progression in these patients, but we need more time to determine whether it improves survival,” he said. “This also applies to the role of local radiotherapy directed to the primary prostate cancer where we need longer follow-up to establish whether and how to best combine it with systemic treatments.”