Matthew Smith, MD, Professor of Medicine of Harvard Medical School and Director of the Genitourinary Malignancies Program at Massachusetts General Hospital Cancer Center discusses the U.S. FDA Approves Addition of Overall Survival and Other Secondary Endpoint Data to NUBEQA® (darolutamide) Prescribing Information.
Phase III results showed that NUBEQA care resulted in a 31 percent reduction in death risk, with a statistically significant increase in overall survival (OS) relative to placebo (HR=0.69, 95 percent CI 0.53-0.88; p=0.003), giving men with non-metastatic castration-resistant prostate cancer (nmCRPC) the chance to prolong their lives.
For men living with nmCRPC, time to pain progression, a primary-secondary endpoint, is significant and an important factor in treatment decisions1
With longer-term follow-up, the final study improved the safety profile of NUBEQA1,22
WHIPPANY, N.J."(BUSINESS WIRE)"It was announced today by Bayer that the U.S. A supplementary New Drug Application (sNDA) was approved by the Food and Drug Administration (FDA) to add overall survival (OS) and other secondary endpoint details from the Phase III ARAMIS trial to the Prescription Information for NUBEQA® (darolutamide). NUBEQA dramatically decreased the probability of death by 31%, giving prolonged life to men with non-metastatic castration-resistant prostate cancer (nmCRPC) with a higher chance of living longer. Additional information involves time for the development of pain and time for cytotoxic chemotherapy to begin. Also revised to provide additional guidelines on drug reactions was the Prescription Details. With an extended follow-up of a median of 29 months for the overall study population, the final review improved the safety profile of NUBEQA.1,22
The presentation of these data at the American Society of Clinical Oncology (ASCO) 2020 Virtual Science Program and subsequent publication in The New England Journal of Medicine on September 10 is followed by the revised Prescribing Information.
Data from the Phase III ARAMIS Trial Primary and Final Analyses
The previously reported findings showed a highly significant increase in the primary efficacy endpoint of metastasis-free survival (MFS) in 1,509 patients from the Phase III ARAMIS study, with a median of 40.4 months (n=955) of NUBEQA plus androgen deprivation therapy (ADT) compared to 18.4 months (n=554) of placebo plus ADT (p<0.001). MFS is described as the period from randomization to the first evidence of Blinded Independent Central Review (BICR)-confirmed distant metastasis or any cause of death within 33 weeks of the last assessable scan, whichever occurred first.
The proven tolerability of NUBEQA was confirmed by the three more commonly occurring adverse reactions in the NUBEQA arm (approximately 2% over placebo): fatigue (16% versus 11%), extremity pain (6% versus 3%), and rash (3 percent versus 1 percent ). In women, NUBEQA has not been studied and there are a warning and precaution about embryo-fetal toxicity.
Phase III ARAMIS Trial Secondary Outcome Details Now Used in Prescribing Knowledge
Men with nmCRPC receiving NUBEQA plus ADT demonstrated a statistically significant increase in OS relative to placebo plus ADT in the Phase III ARAMIS study, with a 31 percent decrease in death risk (HR=0.69, 95 percent CI 0.53-0.88; p=0.003). OS was statistically important despite the crossing over to NUBEQA of 31 percent (n=170) of patients in the ADT arm. In total, prior to this study, 55 percent (n=307) of patients in the ADT arm crossed over to NUBEQA or underwent another life-prolonging treatment.
Statistical importance was also demonstrated by other secondary endpoints incorporated in the Prescription Information for NUBEQA, including delaying time to development of pain (HR=0.65, 95% CI 0.53-0.79; p<0.0001) and time to initiation of cytotoxic chemotherapy (HR=0.58, 95% CI 0.44-0.76; p<0.0001).
Time to progression of pain was described as at least a 2-point worsening of the pain score from baseline on Brief Pain Inventory-Short Form or Opioid Initiation and was recorded in 28% of all study patients.
The Prescribing Information was not revised to reflect any new safety signals found in the final study. To include additional medication reactions, the Prescription Information was revised. NUBEQA inhibits transporters OATP1B1 and OATP1B3. Plasma concentrations of OATP1B1 or OATP1B3 substrates can be increased by concomitant use. Check for adverse effects more regularly and consider the dosage reduction of these substrates.