Erleada-Zytiga Combo Delays Progression in mCRPC Patients, Phase 3 Trial Reports

Erleada-Zytiga Combo Delays Progression in mCRPC Patients, Phase 3 Trial Reports

Combining Erleada (apalutamide) and Zytiga (abiraterone acetate) to treat metastatic castration-resistant prostate cancer (mCRPC) significantly extends the time patients live without signs of disease worsening, compared with Zytiga alone, Janssen announced in a press release.

Findings from the ACIS Phase 3 trial (NCT02257736), which enrolled patients on androgen deprivation therapy (ADT) who had not been treated with chemotherapy, also showed that the combination led to stronger responses and a trend toward better overall survival.

Trial’s findings were presented in the oral presentation, “Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC),” at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, held online Feb. 11–13.

Erleada and Zytiga, both developed by Janssen, belong to a form of hormone therapy that blocks the androgen receptor, preventing male hormones, or androgens, from sending chemical signals that stimulate cancer growth.

The two are approved for mCRPC patients — those who no longer respond to androgen-lowering treatments, such as ADT, and whose cancer has spread to other parts of the body. But because they inhibit the interaction between androgens and the androgen receptor in distinct ways, researchers investigated whether their use in combination could lead to better outcomes.

ACIS enrolled 982 men with mCRPC who had not received chemotherapy, and randomly assigned them to either a triple combination of Erleada, Zytiga, and the corticosteroid prednisone, or to Zytiga and prednisone only (the control group). All were taken as daily tablets for up to five years.

The trial met its primary goal of radiographic progression-free survival, meaning that patients on the Erleada combination lived significantly longer without signs of radiographic disease progression (22.6 months) than those on the control group (16.6 months). This six-month extension represented a 31% reduction in the risk of radiographic disease progression or death.

Such reduction was maintained in the long term, as patients on the triple combination were 30% less likely to have progressed or died after a median follow-up of 54.8 months (about 4.5 years).

At the time of this final analysis, more patients on the combination also attained responses to treatment (79.5% vs. 72.9%), defined as a reduction in prostate-specific antigen (PSA) levels, a marker of prostate cancer, by 50% or more.

Other secondary endpoints, including overall survival, time to initiation of chemotherapy, use of chronic opioids, and pain progression, did not differ significantly between the two treatment groups.

Individuals in both groups also reported similar quality of life results, as measured by the Functional Assessment of Cancer Therapy–Prostate. This standard survey assesses patients’ physical, social and family, emotional, and functional well-being, as well as measures specific to prostate cancer.

The combination’s safety profile was consistent with that seen in prior Erleada studies. No new safety concerns arose during the study.

Severe to life-threatening treatment-related side effects occurred in 63.3% of participants in the combination arm, and 56.2% in the control arm. Those reported more frequently in the combination arm included fatigue, high blood pressure, falls, skin rash, heart disorders, fractures and osteoporosis, and seizures.