Erleada Cuts Risk of Death by 25% in Localized Castration-resistant Prostate Cancer, Phase 3 Trial Finds

Add-on treatment with Erleada (apalutamide) lowers the risk of death by 25% in men on androgen deprivation therapy (ADT) for non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastases, according to updated results of a Phase 3 trial.

The research, “Apalutamide (APA) and Overall Survival (OS) in Patients (pts) With Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC): Updated Results From the Phase 3 SPARTAN Study,” was presented at the 2019 European Society for Medical Oncology (ESMO) Congress and published in the journal Annals of Oncology.

The double-blind, placebo-controlled, and multicenter SPARTAN trial (NCT0194620) included 1,207 nmCRPC patients with rapidly rising prostate-specific antigen (PSA) levels, as assessed with a PSA Doubling Time of up to 10 months. (PSA Doubling Time refers to the period needed to double the blood level of PSA, and is a common predictor of cancer progression and survival.)

Of these people, 806 were given a combination of once-daily Erleada (240 mg) and ADT, and 401 were treated with ADT and a placebo.

In a prior analysis, which led to Erleada’s approval in both the U.S. and the E.U. for this patient population, researchers showed that Erleada extended the time patients lived without their disease spreading by more than two years — 40.5 months (combo group) versus 16.2 months (placebo group) — representing a 72% reduction in the risk of disease spread or death.

At that time, survival results were not mature enough to assess Erleada’s superiority. Investigators now report that, after a median follow-up of 41 months, Erleada reduced the risk of death by 25% compared to ADT only.

In fact, 72% of patients on Janssen Oncology’s Erleada reached the four-year mark alive, compared to 65% of those on ADT only. A similar difference favoring Erleada was also found when accounting for the 76 patients initially on placebo and who switched to Erleada treatment after no evidence of disease progression.

Erleada also provided a significantly longer time without disease worsening after a subsequent therapy – 55.6 vs. 43.8 months. At four years, 64% of the patients given Erleada were free from cancer progression on a subsequent therapy, compared to 45% of those who had received ADT only.

The lower risk of death was consistent across subgroups defined by race, prior treatments, or baseline prostate-specific antigen (PSA) levels. The proportion of patients receiving subsequent life-prolonging treatment was 68% in the placebo group and 40% in the Erleada group.

“Longer-term analyses help to present a more complete picture of a medication’s benefits and potential risks over time. This updated SPARTAN analysis shows an important survival benefit,” Matthew Smith, MD, PhD, SPARTAN’s co-principal investigator and director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center, said in a press release.

“These results add to the evidence supporting apalutamide [Erleada] as a standard option for treating patients with non-metastatic castration-resistant prostate cancer who remain at high risk of their cancer spreading,” added Smith, also a professor of medicine at Harvard Medical School.

Rates of treatment-related adverse events in patients on Erleada were consistent with those previously reported. Side effects were reported in 14% of those given Erleada and in 8% of those not using it. Among the most common adverse events were fatigue, high blood pressure, rash, diarrhea, nausea, and weight loss.

Erleada is an oral treatment targeting the androgen receptor and blocking its activation by androgens such as testosterone. ADT, a standard prostate cancer treatment, lowers the amount of androgens in the body.

Margaret Yu, MD, Janssen Research & Development’s vice president and prostate cancer disease area leader, mentioned the five ongoing Phase 3 trials testing Erleada in prostate cancer. “Together, these trials highlight Janssen’s commitment to making prostate cancer a manageable disease,” she said.

The U.S. Food and Drug Administration recently approved Erleada to treat metastatic castration-sensitive prostate cancer patients, or those whose cancer still responds to ADT.

Of note, SPARTAN was funded by Johnson & Johnson-owned Aragon Pharmaceuticals and Janssen Research and Development (also owned by Johnson & Johnson). Nine of this study’s authors received funding or speaker/consulting fees from Janssen Oncology, or were members of advisory boards for this company. Five were employees of Janssen Oncology and/or stockholders of Johnson & Johnson.