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Among patients with high-risk nonmetastatic prostate cancer, 2-year outcomes showed a sustained survival benefit with treatment involving abiraterone acetate (Zytiga) and prednisolone (AAP) with or without enzalutamide (Xtandi) added to androgen deprivation therapy (ADT).1
Results from a combined analysis of the multistage STAMPEDE trial (NCT00268476) presented during the 2021 ESMO Congress demonstrated that for patients in the AAP-based therapy groups, metastasis-free survival (MFS) was improved versus those in the ADT alone group (HR, 0.53; 95% CI, 0.44-0.64; P = 2.9 × 10-11), for a 6-year rate improvement from 69% to 82%.
“We show that 2 years of abiraterone [acetate]–based therapy significantly improves metastasis-free survival and overall survival of high-risk nonmetastatic prostate cancer starting androgen deprivation therapy and should be now considered a new standard of care,” Gerhardt Attard, MD, FRCP, PhD, a clinician scientist and team leader at University College London Cancer Institute, and honorary medical oncology consultant at University College London Hospital, explained in his presentation of the data.
Eligible patients needed to have histologically confirmed prostate adenocarcinoma, intention to treat with long-term ADT, a WHO performance score of 0 to 2, and provided written consent. All patients received standard-of-care ADT for 3 years plus local radiotherapy with no overlapping controls.
Results of the STAMPEDE trial previously showed that patients with metastatic prostate cancer benefit from the addition of AAP to ADT; however, results in the nonmetastatic setting are still under investigation.2 This multistage, multiarm, phase 2/3 platform trial continued long-term follow-up in nonmetastatic patients from 2017 but did not record any further efficacy data on this cohort.
A total of 1974 patients were randomized 1:1 to each treatment arm, with patient baseline characteristics that were well-balanced. The median age was 68 years, the median PSA level was 34 ng/mL, 39% of the population was node-positive, and 3% had relapsed after prior treatment. Total median follow-up was 72 months, but follow-up was longer for the AAP versus APP plus enzalutamide comparison (85 vs 60 months).
The prespecified subgroup analysis by randomization period did not find any significant evidence for differing effect between the AAP plus ADT (HR, 0.54; 95% CI, 0.43-0.68; P = 3.2 × 10-7) and AAP and enzalutamide plus ADT groups (HR, 0.53; 95% CI, 0.39-0.71; P = 2.1 × 10-5).
“This is in keeping with reports [of patients with] metastatic castration-resistant prostate cancer reported after we completed accrual that have shown no benefit in overall survival for this combination,” explained Attard in his presentation. “This really gives us 2 groups that independently confirm the benefit of abiraterone-based treatment in this population.”
There was no statistically significant evidence of treatment effect heterogeneity observed among baseline randomization factors including nodal status, age at randomization, WHO performance status at randomization, regular NSAID/aspirin use at baseline, or use of radiation therapy as part of treatment.
In the overall survival examination, significant benefit of either AAP-based regimen versus ADT alone was noted (HR, 0.60; 95% CI, 0.48-0.73; P = 9.3x10-7), resulting in absolute benefit 6-year rate improvement from 77% to 86%.
No statically significant overall survival difference was seen in the subgroup analysis by randomization period for the AAP vs AAP plus enzalutamide groups, with hazard ratios of 0.63 (95% CI, 0.48-0.82; P = .0005) and 0.54 (95% CI, 0.39-0.76; P = .00043), respectively.
Regarding prostate cancer–specific survival, there was a benefit noted in the AAP-based treatment arms vs ADT alone (HR, 0.49; 0.37-0.65; P = 1.3 × 10-6). For progression-free survival, data favored the AAP-based therapy regimens (HR, 0.44; 95% CI, 0.36-0.54; P = 5.2 × 10-15).
In the first 2 years of treatment, 118 grade 3 adverse effects (AEs) were reported in the ADT alone group compared with 151 events in the AAP-based treatment group. Grade 4 or higher AEs were seen in 12 and 17 patients from the ADT alone and ADT plus AAP groups, respectively. Adding enzalutamide to AAP treatment increased toxicities in patients with no significant improvement in efficacy.
1. Attard G, Brown L, Clarke N, et al. Abiraterone acetate plus prednisolone (AAP) with or without enzalutamide (ENZ) added to androgen deprivation therapy (ADT) compared to ADT alone for men with high-risk non-metastatic (M0) prostate cancer (PCa): Combined analysis from two comparisons in the STAMPEDE platform protocol. Presented at: 2021 European Society for Medical Oncology Congress. September 16-21, 2021. Abstract LBA4.
2. James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N Engl J Med. 2017;377(4):338-351. doi:10.1056/NEJMoa1702900