Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of the primary results of two phase 3 randomized controlled trials of the STAMPEDE platform protocol

Fund

Men with high-risk non-metastatic prostate cancer are treated with androgen deprivation therapy (ADT) for 3 years, often combined with radiation therapy. We analyzed new data from two Phase 3 randomized controlled trials conducted in a multi-arm, multi-step platform protocol to assess the effectiveness of adding abiraterone and prednisolone alone or with enzalutamide to ADT in this patient population.

Methods

These open-label phase 3 trials were carried out at 113 sites in the United Kingdom and Switzerland. Eligible patients (no age restriction) were at high risk (defined as node positive or, if node negative, having at least two of the following characteristics: tumor stage T3 or T4, Gleason sum score of 8 to 10, and antigen prostate specific [PSA] concentration ≥40 ng / mL) or relapse with high-risk characteristics (≤12 months of total ADT with interval ≥12 months without treatment and PSA concentration ≥4 ng / mL with doubling time from ClinicalTrials.gov, NCT00268476 , and from the ISRCTN registry, ISRCTN78818544.

Results

Between November 15, 2011 and March 31, 2016, 1974 patients were randomized to receive treatment. The first trial assigned 455 to the control group and 459 to the combination treatment, and the second trial, which included enzalutamide, assigned 533 to the control group and 527 to the combination treatment. The median age in all groups was 68 years (IQR 63–73) and the median PSA 34 ng / ml (14.7–47); 774 (39%) of 1974 patients were lymph node positive and 1684 (85%) were scheduled for radiotherapy. With a median follow-up of 72 months (60-84), there were 180 metastasis-free survival events in the combination therapy groups and 306 in the control groups. Metastasis-free survival was significantly longer in the combination therapy groups (median not reached, IQR not assessable [NE]–NE) only in control groups (not reached, 97 – NE; risk ratio [HR] 0.53, 95% CI 0.44-0.64, p I2 p = 090). Overall survival (median not reached [IQR NE–NE] in combination therapy groups vs not reached [103–NE] in control groups; HR 0.60, 95% CI 0.48-0.73, p vs not reached [NE–NE]; 0.49, 0.37-0.65, p vs 86 months [83–NE]; 0.39, 0.33-0.47, p vs not reached [103–NE]; 0.44, 0.36-0.54, p

Interpretation

In men with high-risk non-metastatic prostate cancer, combination therapy is associated with significantly higher rates of metastasis-free survival compared to ADT alone. Abiraterone acetate in combination with prednisolone should be considered a new standard treatment for this population.

Funding

Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen and Astellas.


Source link

Comments are closed.