Clinical trialProstate cancer

Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy

N Engl J Med · 20171917 patients

James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, et al. N Engl J Med. 2017. 377:338-351

A newer report of this study has been published: Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol (2022)

Study type: Clinical trial
Study name: STAMPEDE
Design: Randomised trial with a multi-arm, multistage design, with 1:1 randomisation
Sample size: 1917 patients
Source: N Engl J Med · 2017
Trial registration: NCT00268476

In plain words

In this large study, men who were just starting hormone therapy (androgen deprivation) for advanced or spread prostate cancer received either hormone therapy alone or hormone therapy plus the drug abiraterone with prednisolone. Adding abiraterone helped patients live longer and delayed the growth of the disease. On the other hand, serious side effects were more common in the abiraterone group, so the treatment decision should be made together with your doctor, taking each patient's situation into account.

Key results

184 in the combination group vs 262 in the ADT-alone group

Number of deaths

HR 0.63; 95% CI 0.52 to 0.76; P<0.001

0.75 in non-metastatic disease and 0.61 in metastatic disease

Hazard ratio for death by metastatic status

248 in the combination group vs 535 in the ADT-alone group

Treatment failure events

HR 0.29; 95% CI 0.25 to 0.34; P<0.001

0.21 in non-metastatic disease and 0.31 in metastatic disease

Hazard ratio for treatment failure by metastatic status

Drugs in this study:Abiraterone (Zytiga)

Dose and schedule cards

Radiotherapy + ADT + 2 years of abiraterone (STAMPEDE)

High-risk non-metastatic prostate cancer: nodal involvement, or at least two of T3/T4, Gleason 8 to 10, PSA ≥40 ng/mL (or relapse with high-risk features); WHO performance status 0 to 2Cycle length: ContinuousOn the page “Prostate cancer” · Backbone hormone therapy, high-risk localized disease and biochemical recurrence

High-risk non-metastatic prostate cancer: nodal involvement, or at least two of T3/T4, Gleason 8 to 10, PSA ≥40 ng/mL (or relapse with high-risk features); WHO performance status 0 to 2

Drug	Dose	Route	Schedule
ADT	Per formulation	—	Continuous for 3 years
Abiraterone acetate	1000 mg once daily	Oral, on an empty stomach	Daily for 2 years
Prednisolone	5 mg once daily	Oral	Daily with abiraterone
Radiotherapy to the prostate and seminal vesicles	74 Gy in 37 fractions or a hypofractionated equivalent	External-beam radiotherapy	Mandatory for N0 and recommended for N+

Cycle length: Continuous
Duration: Abiraterone for 2 years or until progression; ADT for 3 years (until progression if radiotherapy is not given)

STAMPEDE trial regimen; adding enzalutamide concurrently gave no benefit and only increased toxicity. In this regimen, prednisolone 5 mg is given once daily.

On the page “Prostate cancer” · Backbone hormone therapy, high-risk localized disease and biochemical recurrence

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1ADT alone

Androgen deprivation therapy (ADT) alone. Local radiotherapy was mandatory for node-negative non-metastatic patients and recommended for node-positive patients.

2ADT plus abiraterone and prednisolone (combination therapy)

ADT plus abiraterone acetate 1000 mg and prednisolone 5 mg orally once daily. In non-metastatic patients without planned radiotherapy and in metastatic patients, treatment continued until radiological, clinical or PSA progression; otherwise for up to 2 years or until any progression, whichever came first. Patients in the combination group were assessed at least every 3 months.

Source of the regimen details: Full text of the paper (PMC5533216)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

1917 men starting long-term ADT for newly diagnosed metastatic, node-positive, or high-risk locally advanced prostate cancer (at least two of: stage T3 or T4, Gleason score 8 to 10, PSA ≥40 ng/mL), or high-risk relapse after radical surgery or radiotherapy. 52% metastatic, 20% non-metastatic with positive or indeterminate nodes and 28% non-metastatic node-negative; 95% newly diagnosed; median age 67 years and median PSA 53 ng/mL.

Endpoints

Primary endpoint: overall survival. Intermediate primary endpoint: failure-free survival (treatment failure defined as radiological, clinical or PSA progression or death from prostate cancer).

Safety and side effects

Grade 3 to 5 adverse events over the whole trial: 47% (443 of 948) in the combination group with 9 grade 5 events, versus 33% (315 of 960) in the ADT-alone group with 3 grade 5 events. The main additional adverse events: hypertension, mild elevation of aminotransferases and respiratory disorders. In patients without progression in the first year, the prevalence of grade 3 or higher adverse events was 15% versus 11%.

Clinical significance and place in guidelines

These results show that adding abiraterone and prednisolone to ADT at the start of treatment in men with locally advanced or metastatic prostate cancer improves overall survival and failure-free survival compared with ADT alone. The exact place of this approach in treatment guidelines and its regulatory approval status should be checked separately.

Limitations

According to the abstract, grade 3 to 5 adverse events were more frequent in the combination group. Other limitations are not reported in the abstract and should be checked in the full text.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.