Clinical trialPhase 3Prostate cancer

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer

N Engl J Med · 20171199 patients

Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, et al. N Engl J Med. 2017. 377:352-360

A newer report of this study has been published: Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial (2019)

Study type: Clinical trial
Study name: LATITUDE
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial
Sample size: 1199 patients
Source: N Engl J Med · 2017
Trial registration: NCT01715285

In plain words

In this study, men who had just been diagnosed with prostate cancer that had spread, and whose disease still responded to hormone therapy, were given abiraterone with prednisone in addition to the usual hormone therapy. This combination helped patients live longer and stay longer without the disease growing on scans. Side effects such as high blood pressure and low blood potassium were seen more often in the abiraterone group.

Key results

Median not reached vs 34.7 months

Median overall survival

Hazard ratio for death 0.62; 95% CI 0.51–0.76; P<0.001

33.0 months vs 14.8 months

Median radiographic progression-free survival

Hazard ratio for disease progression or death 0.47; 95% CI 0.39–0.55; P<0.001

Better results in the abiraterone group

Secondary endpoints (time to pain progression, subsequent therapy, start of chemotherapy, PSA progression)

P<0.001 for all comparisons

Better result in the abiraterone group

Subsequent symptomatic skeletal events

P=0.009

Drugs in this study:Abiraterone (Zytiga)

Dose and schedule cards

ADT + abiraterone + prednisone (LATITUDE)

mHSPC; in LATITUDE, newly diagnosed disease with at least 2 high-risk factors (Gleason ≥8, ≥3 bone lesions, measurable visceral metastases); ECOG 0 to 2Cycle length: ContinuousOn the page “Prostate cancer” · Metastatic hormone-sensitive disease (mHSPC)

mHSPC; in LATITUDE, newly diagnosed disease with at least 2 high-risk factors (Gleason ≥8, ≥3 bone lesions, measurable visceral metastases); ECOG 0 to 2

Drug	Dose	Route	Schedule
Abiraterone acetate	1000 mg once daily	Oral, fasting (no food for 2 h before and 1 h after the dose); swallow tablets whole	Daily
Prednisone	5 mg once daily	Oral	Daily
ADT (GnRH agonist or antagonist, or prior orchiectomy)	Per formulation	—	Continuous

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Dose per the FDA label and the trial.

On the page “Prostate cancer” · Metastatic hormone-sensitive disease (mHSPC)

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

1Abiraterone group

ADT (LHRH agonist or surgical castration) plus abiraterone acetate 1000 mg orally once daily (4 tablets of 250 mg) and prednisone 5 mg orally once daily, until disease progression or unacceptable toxicity (597 patients).

2Placebo group

ADT plus two placebos matching abiraterone and prednisone (602 patients).

Source of the regimen details: ClinicalTrials.gov NCT01715285 and the FDA label for ZYTIGA (DailyMed)

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

1199 men with newly diagnosed metastatic prostate cancer (within 3 months before randomisation) and at least 2 of three high-risk factors: Gleason score 8 or higher, 3 or more lesions on bone scan, measurable visceral metastasis (excluding lymph nodes); ECOG performance status 0 to 2. Up to 3 months of previous ADT was allowed; brain metastases and AST/ALT ≥2.5 times the upper limit of normal or liver metastases were exclusion criteria.

Endpoints

Primary endpoints: overall survival and radiographic progression-free survival. Secondary endpoints included time to pain progression, subsequent prostate cancer therapy, start of chemotherapy, PSA progression and subsequent symptomatic skeletal events.

Safety and side effects

According to the paper, grade 3 hypertension and hypokalaemia were more frequent in the abiraterone group. According to the FDA label (median duration of treatment 24 months): hypertension 37% (grade 3–4: 20%) versus 13% (10%); hypokalaemia 20% (grade 3–4: 10%) versus 3.7% (1.3%); grade 3–4 ALT increase: 5.5% versus 1.3%.

Clinical significance and place in guidelines

This trial showed that adding abiraterone and prednisone to androgen deprivation therapy in newly diagnosed metastatic castration-sensitive prostate cancer improves overall survival and radiographic progression-free survival. Regulatory approval status and current guideline recommendations should be checked separately, as the abstract does not address them.

Limitations

The overall survival results come from a planned interim analysis with a median follow-up of 30.4 months. On the recommendation of the data and safety monitoring committee, the trial was unblinded and patients in the placebo group were allowed to cross over to abiraterone. Other limitations are not mentioned in the abstract.

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.