Men diagnosed with non-metastatic castration-resistant prostate cancer live longer if they are treated with darolutamide (Nubeqa) than placebo, the final results of the phase III ARAMIS trial revealed, researchers said at the virtual annual meeting of the American Society of Clinical Oncology.
About 15.5% of the patients who were treated with darolutamide died compared with 19.1% of the placebo patients — a 31% relative risk reduction that achieved statistical significance (P=0.003), Neal Shore, MD, medical director of the Atlantic Urology Clinics, Myrtle Beach, South Carolina, told BreakingMED.
Shore and colleagues enrolled 1,509 patients who were diagnosed with non-metastatic castration-resistant prostate cancer. “Non-metastatic castrate resistant prostate cancer occurs frequently among men who have a rising prostate specific antigen (PSA) test yet there is no imaging evidence of metastasis,” Shore explained.
“These are typically patients who had high-risk, localized, newly-diagnosed prostate cancer who underwent prostatectomy or radiation or a combination of both, yet still had a rising PSA,” he said. “These patients are typically started on a testosterone-suppressive medication and that lowers the PSA. Over a period of years or months, the PSA starts going up, and if there is still no imaging confirmation of a lesion, that is called non-metastatic castrate-resistant prostate cancer,” Shore said. “These men have micro-metastatic disease.”
He said treatment with darolutamide is aimed at preventing these micro-metastases from becoming tumors. The men were treated with darolutamide 600 mg twice a day versus placebo control. All the patients continued with their androgen-deprivation therapy.
“Previously we reported that the study met its primary endpoint of metastasis-free survival, and we also reported a trend towards overall survival,” Shore said. In addition to demonstrating the survival benefit, he said, “Taking this drug, not only delays radiographic progression but it also improves survival. We had previously reported that treatment with darolutamide slowed the time for the need of cytotoxic chemotherapy, slowed progression to pain and to skeletal events.
“When people say, ’Why take a drug when you don’t have any tumor burden?’ this is the reason why,” Shore added.
The drug is well tolerated, he said. “There was some increase in fatigue but there was no increased risk of cognitive impairment, of seizures, of falls or of fractures or of hypertension or of rash. I am using this drug now among my patients.”
In commenting on the study, Manish Vira, MD, system chief of urology for Northwell Cancer Institute, Lake Success, New York, and vice chair of the Arthur Smith Institute for Urology, New Hyde Park, New York, told BreakingMED, “Treatment options for non-metastatic castrate resistant prostate cancer patients remains controversial. Currently, most guidelines recommend treatment for patients with short PSA doubling times, that is less than 10 months, but these patients often progress to overt metastatic disease in a short period of time.
“Furthermore, with the development of prostate cancer specific imaging modalities, our ability to detect micrometastatic prostate cancer locations is improving,” Vira said. “That being said, given these trial results along with prior studies using second generation anti-androgen medications, the evidence is becoming stronger that initiation of these medications early in castrate resistant prostate cancer results in delay to symptomatic metastasis and perhaps, based on the current study, improvement in overall survival.
“However, the high monthly cost of these medications remains a limitation for more universal use in these patients,” he added.
Darolutamide was approved by the FDA in 2019.
Edward Susman, Contributing Writer, BreakingMED™
The ARAMIS trial was funded by Bayer AG and Orion Pharma.
Shore disclosed relevant relationships with Amgen; AstraZeneca; Bayer; Dendreon; Ferring; Genentech/Roche; Janssen Scientific Affairs; Medivation/Astellas; Myovant Sciences; Pfizer; and Tolmar.
Vira disclosed no relevant relationships with industry.
Cat ID: 172
Topic ID: 98,172,728,791,730,116,122,25,192,73,481,163,172