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Practice-changing data: Abiraterone plus ADT improves OS in prostate cancer

According to findings from the LATITUDE and STAMPEDE trials presented at this year´s ASCO, adding abiraterone to androgen-deprivation therapy (ADT) increased overall survival (OS) among men with locally advanced or hormone-sensitive metastatic prostate cancer and has the potential to become the new standard of care for men starting long-term ADT.

Results of both STAMPEDE and LATITUDE were published immediately following the Plenary Session in the New England Journal of Medicine.

Background: Approximately 3% to 5% of men diagnosed with prostate cancer have metastasis at diagnosis in Western countries; in some large countries in Asia, however, that incidence can be as high as 60%. Historically, ADT has been the standard of care for patients with hormone-sensitive, locally advanced or metastatic disease, and in the past several years docetaxel has been added to that therapy for patients with high metastatic burden. However, many pts are not candidates for docetaxel and may benefit from alternative therapy.

The STAMPEDE trial

This ongoing trial opened in 2005 and is the largest randomized clinical trial of treatments for prostate cancer. Its multistage, multi-arm platform design allows for adaption and addition of new therapies. The abiraterone comparison arm of STAMPEDE was opened in 2011 and closed January 2014. Enrolled patients included those with high-risk locally advanced or metastatic prostate cancer that were newly diagnosed or relapsed after radical prostatectomy or radiation therapy and who were starting ADT. 1,917 Patients were randomized 1:1 to receive standard of care (ADT with radiation therapy if eligible) or ADT plus abiraterone and prednisolone (AP-ADT). The primary outcome measure was death by any cause; median follow-up was 40 months.

In the abiraterone group, OS was improved by 37% compared with the standard-of-care group (HR 0.63; p = 0.00000115). The improvement in failure-free survival (FFS) was even more pronounced with a HR of 0.29.

Regarding safety, the number of grade 3 to 5 adverse events was similar in most categories, although the abiraterone group reported more cardiovascular disorders than the standard-of-care group (10% vs. 4%, respectively) and more hepatic disorders (7% vs. 1%, respectively).

Presenting author Dr. Nicholas D. James and discussant Dr. Tanya B. Dorff state, that the results of the STAMPEDE trial were practice-changing findings and that ADT (± radiotherapy) plus abiraterone is a new standard of care in this patient cohort.

The LATITUDE trial

The LATITUDE trial evaluates the clinical benefit of early intervention with abiraterone acetate and prednisolone (AA+P) added to ADT in newly diagnosed (≤ 3 months prior to randomization), high risk (≥ 2 of 3 risk factors: Gleason ≥ 8, ≥ 3 bone lesions, measurable visceral metastases), hormone-sensitive metastatic prostate cancer. Dr. Karim Fizazi presented results of the first planned interim analysis, which is now to be the final analysis due to the positive results, at Sunday´s plenary session.

The trial randomly assigned 1,199 patients to receive ADT plus placebo (n = 602) or ADT plus abiraterone and prednisone (n = 597). After a median follow-up of 30.4 months, the median OS with ADT and placebo was 34.7 months, but was not yet reached in the abiraterone group (HR 0.62, p < 0.0001). The OS rate at 3 years was 66% with abiraterone and prednisone, and 49% without.

The co-primary endpoint radiographic progression-free survival (rPFS) was met as well, with median rPFS of 14.8 months (placebo) compared with 33.0 months with abiraterone (HR 0.47, p < 0.0001). The study regimen had a favorable risk/benefit ratio and the results support early intervention with AA+P in newly diagnosed, high-risk hormone-sensitive metastatic prostate cancer.

References:

James ND et al., abstract LBA5003: Adding abiraterone for men with high-risk prostate cancer (PCa) starting long-term androgen deprivation therapy (ADT): Survival results from STAMPEDE (NCT00268476).

James ND et al., NEJM 2017; DOI: 10.1056/NEJMoa1702900

Fizazi K et al., abstract LBA3: LATITUDE: A phase III, double-blind, randomized trial of androgen deprivation therapy with abiraterone acetate plus prednisone or placebos in newly diagnosed high-risk metastatic hormone-naive prostate cancer.

Fizazi K et al., NEJM 2017; DOI: 10.1056/NEJMoa1704174

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