Apalutamide or enzalutamide added to standard treatment improves survival of patients with metastatic castration-sensitive prostate cancer (mCSPC), according to study findings presented at the 2019 American Society of Clinical Oncology annual meeting in Chicago.

The findings are from the phase 3 TITAN trial, which compared apalutamide plus androgen deprivation therapy (ADT) with ADT alone, and the phase 3 ENZAMET trial, which compared enzalutamide plus standard of care (ADT with or without docetaxel) with standard of care alone. The fi ndings from both trials were published in the New England Journal of Medicine (NEJM).

In the TITAN trial, men who received apalutamide plus ADT experienced a significant 52% decreased risk of death or radiographic progression compared with those who received placebo plus ADT, Kim N. Chi, MD, of BC Cancer and Vancouver Prostate Centre in Vancouver, British Columbia, and colleagues reported. The apalutamide-treated patients also had a significant 33% decreased risk of death. Median radiographic progression-free survival (rPFS) was 22.1 months in the placebo arm and not reached in the apalutamide group. Median overall survival was not reached in either study arm.

In addition, apalutamide recipients had a significant 61% decreased risk of initiating cytotoxic chemotherapy, according to investigators.


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Based on study findings, the trial’s independent monitoring committee recommended unblinding to allow patients in the placebo group to cross over to the apalutamide arm.

In the TITAN (Targeted Investigational Treatment Analysis of Novel Anti-androgen) trial, Dr Chi and colleagues randomly assigned 525 patients to receive apalutamide 240 mg per day plus ADT and 527 to receive placebo plus ADT. Patients had a median age of 68 years. Of the entire study population, 16.4% had undergone prostatectomy or received radiotherapy, 10.7% had received prior docetaxel therapy, and 62.7% had high-volume disease.

At the first interim analysis, with a median 22.7 months of follow-up, the proportion of men with rPFS at 24 months was 68.2% in the apalutamide arm and 47.5% among placebo recipients. At 24 months, the overall survival rate was significantly higher in the apalutamide than placebo group: 82.4% vs 73.5%.

The rates of grade 3 or 4 adverse events were similar in the apalutamide and placebo groups: 42% and 41%, respectively. The rates of study discontinuation due to AEs were 8% and 5%, respectively.

Based on the TITAN findings, Janssen Pharmaceutical Companies, which developed apalutamide (Erleada), submitted a supplemental New Drug Application to the FDA seeking approval of apalutamide for the treatment of men with mCSPC. Apalutamide already is approved the treatment of nonmetastatic castration-resistant prostate cancer.

In the ENZAMET trial, enzalutamide plus standard care with traditional nonsteroidal anti-androgens (NSAA), namely flutamide, bicalutamide, or nilutamide, with or without docetaxel was associated with a significant 33% decreased risk of death compared with standard care alone, Christopher J. Sweeney, MBBS, of the Dana-Farber Cancer Institute in Boston, and colleagues reported. The 3-year overall survival (OS) rate was 80% in the enzalutamide group compared with 72% in the group receiving standard care only. In addition, at 3 years, 64% of the enzalutamide arm remained on study treatment compared with 36% of patients receiving standard of care alone.

“Physicians and patients with prostate cancer now have a new treatment option with enzalutamide, and this is especially relevant for men who cannot tolerate chemotherapy and have a lower burden of disease seen on scans,” Dr Sweeney said in an ASCO press release.

The decreased risk of death associated with enzalutamide treatment was more pronounced in men with low-volume disease and in those without planned docetaxel treatment, investigators reported. Among patients with low-volume disease, the enzalutamide group had a significant 52% decreased risk of death compared with patients taking other NSAAs, with 3-year OS rates of 90% vs 82%. Among patients with high-volume disease, the enzalutamide group also had a significant 26% decreased risk of death, with 3-year OS rates of 71% vs 63%.

In the patients with no planned early docetaxel therapy, enzalutamide-treated men had a significant 49% decreased risk of death compared with those taking another NSAA, with 3-year OS rates of 83% vs 70%. Among those with planned early docetaxel therapy, the enzalutamide recipients had a non-significant 9% decreased risk of death, with 3-year OS rates of 73% vs 74%.

“Our current data support the claim that early enzalutamide prolongs survival within 3 years in the entire trial population but provide limited support that it prolongs overall survival within 3 years in patients who received early docetaxel treatment,” the investigators wrote in the NEJM paper.