Adding Erleada (apalutamide), Janssen‘s next-generation androgen receptor inhibitor, to androgen deprivation therapy (ADT) can prolong life and extend the time without disease worsening in men with metastatic castration-sensitive prostate cancer, a Phase 3 trial shows.

The findings — which supported Janssen’s application to the U.S. Food and Drug Administration requesting Erleada’s approval for this patient population — were recently revealed during the American Society of Clinical Oncology (ASCO) annual meeting in Chicago.

The presentation was titled “First results from TITAN: A phase III double-blind, randomized study of apalutamide (APA) versus placebo (PBO) in patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) receiving androgen deprivation therapy (ADT),” and findings were simultaneously published in The New England Journal of Medicine.

ADT is one of the mainstays of prostate cancer treatment. It works by reducing the amount of androgens — the so-called “male hormones,” including testosterone — in the body. Because androgens drive the growth of some prostate cancers (the “castration-sensitive” ones, defined by their responsiveness to ADT), this lowering of hormone levels can slow cancer growth.

Erleada works by binding to the androgen receptor, blocking it from being activated by androgens in the body. In theory, this would achieve a similar end, albeit through a slightly different mechanism — yet might combining ADT and Erleada have benefits beyond either alone?

To find out, researchers conducted the TITAN Phase 3 clinical trial (NCT02489318), which was funded by Aragon Pharmaceuticals (now owned by Johnson & Johnson), and Janssen Research and Development (also owned by Johnson & Johnson).

In the trial, people with castration-sensitive prostate cancer that had metastasized (spread) were recruited and were randomly given either Erleada and ADT or a placebo and ADT. Patients were followed for the primary endpoints of progression-free survival — the time a patient lives without disease worsening — and overall survival.

At two years after treatment initiation, both survival outcomes were better among patients receiving Erleada. The percentage of patients living two years or more without disease progression was 68.2% for Erleada and 47.5% for placebo. Similarly, 82.4% of patients on Erleada lived two years or more, compared to 73.5% of those on placebo.

Overall, this translated to a 52% lower risk of disease progression or death, and a 33% lower risk of death among those receiving Erleada.

Patients receiving Erleada also took more time before needing chemotherapy, researchers found.

“This is a major study that showed, for the first time, significantly improved overall survival and delay of disease progression with this novel class of drugs known as ‘potent and direct androgen receptor inhibitor’ in men with advanced prostate cancer,” said Kim Chi, MD, in a press release. Kim is an oncologist at the British Columbia Cancer Agency and associate director of clinical research at the Vancouver Prostate Centre; he also co-authored the study.

The frequency of serious adverse events was similar between the two groups — 19.8% for Erleada and 20.3% for placebo. A total of 42 and 28 patients (8.0% and 5.3%) in each group dropped out of the trial because of adverse events, and adverse events led to deaths in 10 (1.9%) patients in the Erleada group and in 16 (3.0%) patients in the placebo group.

Patients receiving Erleada were more likely than those on placebo to develop a rash of any kind (27.1% versus 8.5%) and were more likely to develop hypothyroidism (6.5% versus 1.1%), though this was typically mild.

With these results, investigators are hopeful that Erleada will be approved for prostate cancer treatment by regulatory bodies.

“Based on the results of this study, we are hopeful that apalutamide will garner approval for newly diagnosed advanced prostate cancer by the United States Food and Drug Administration in the coming months,” said Neeraj Agarwal, MD, another study author who is a physician-scientist at Huntsman Cancer Institute and professor at the University of Utah.