The Committee for Medicinal Products for Human Use recommends extending the use of Janssen’s Erleada (apalutamide), in combination with androgen deprivation therapy (ADT), to treat men with metastatic hormone-sensitive prostate cancer (mHSPC).
CHMP’s positive opinion will now be reviewed by the European Commission, which will have the final word on expanding Erleada’s indication in the European Union.
mHSPC, also known as metastatic castration-sensitive prostate cancer (mCSPC), refers to prostate cancer that has spread to other parts of the body but still responds to ADT, or hormone therapy. Men with this type of prostate cancer tend to have poor outcomes, with a median overall survival of less than five years.
Erleada is an inhibitor of the androgen receptor, blocking its activation by androgens such as testosterone. While also a hormone therapy, it works through a different mechanism than ADT, which reduces the level of androgens in the body, suggesting their combination could be better at extending survival outcomes.
The recommendation by CHMP, an arm of the European Medicines Agency, was based on the TITAN Phase 3 trial (NCT02489318) which showed that Erleada added to ADT — the standard of care for men with mHSPC — prolonged overall survival and the time patients lived without disease worsening, compared to ADT only.
The benefits were seen regardless of tumor volume, prior treatment with docetaxel, or cancer stage at diagnosis.
TITAN, which was funded by Johnson & Johnson‘s Aragon Pharmaceuticals and Janssen, included 1,052 mCSPC patients with a broad range of clinical features: those with low- and high-volume disease, those who were newly diagnosed, and those who had received prior treatment for localized or metastatic disease. The study was run in 23 countries across North America, Latin America, South America, Europe, and Asia Pacific.
Patients were randomized to receive tablets of Erleada (total of 240 mg) or a placebo once daily, plus continuous ADT — in the form of a gonadotropin-releasing hormone analog or surgical castration — until disease progression or unacceptable toxicity related to treatment.
Compared to the placebo plus ADT, combining Erleada with ADT led to a 33% reduction in the risk of death and a 52% reduction in the risk of cancer worsening (as assessed by radiography) or death.
After two years on the trial, 84% of patients on Erleada were still alive, versus 78% of those on placebo.
The safety profile was similar between the two groups, with 42% of severe or life-threatening adverse events observed in the Erleada group versus 41% in the placebo group.
The most common serious adverse events were high blood pressure (8.4% of patients on Erleada vs. 9.1% on placebo) and skin rash (6.3% vs. 0.6%). Eight percent of patients given Erleada left the study due to side effects, compared with 5% receiving placebo.
“Today’s Positive Opinion for apalutamide [Erleada] brings us one step closer to providing a much-needed treatment option for a broad population of patients diagnosed with mHSPC,” Joaquín Casariego, MD, area lead for oncology in Europe, Middle East and Africa at Janssen, said in a press release.
“At this stage of disease, it is critical to intervene with another treatment that can prolong survival and delay progression to the fatal stage, without compromising the quality of life of patients.”
In the United States and the European Union, Erleada is approved for patients with non-metastatic (localized) castration-resistant prostate cancer who are at high risk of developing metastatic disease. The U.S. Food and Drug Administration approved Erleada’s label extension in September 2019 to include men with mHSPC.