- Phase III data showed treatment with NUBEQA resulted in a 31% reduction in risk of death, with a statistically significant improvement in overall survival (OS) compared to placebo (HR=0.69, 95% CI 0.53-0.88; p=0.003), giving men with non-metastatic castration-resistant prostate cancer (nmCRPC) the opportunity to extend their lives1
- Time to pain progression, a key secondary endpoint, is meaningful for men living with nmCRPC and an important consideration in treatment decisions1
- The final analysis reinforced NUBEQA's safety profile with longer term follow-up1,2
San Francisco, CA (UroToday.com) -- Bayer announced that the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) to add overall survival (OS) and other secondary endpoint data from the Phase III ARAMIS trial to the NUBEQA® (darolutamide) Prescribing Information. NUBEQA significantly reduced the risk of death by 31%, offering men with non-metastatic castration-resistant prostate cancer (nmCRPC) extended survival for a greater chance of living longer. Additional data include time to pain progression and time to initiation of cytotoxic chemotherapy. The Prescribing Information was also updated to include additional guidance on drug interactions. The final analysis reinforced NUBEQA's safety profile with an extended follow-up of median 29 months for the overall study population.1,2
The updated Prescribing Information follows the presentation of these data at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program and subsequent September 10 publication in The New England Journal of Medicine.
"A key goal of cancer treatment is to ensure that patients can live longer while minimizing side effects," said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer's Pharmaceutical Division. “NUBEQA has a proven efficacy and safety profile in men with nmCRPC and delayed the effects of disease progression in men who are otherwise generally asymptomatic. This update also gives physicians added certainty that NUBEQA should be prescribed to appropriate patients at nmCRPC diagnosis to help ensure optimal outcomes for these men.”
Data from Primary and Final Analyses of Phase III ARAMIS Trial
Previously published results in 1,509 patients from the Phase III ARAMIS trial demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months (n=955) with NUBEQA plus androgen deprivation therapy (ADT), compared to 18.4 months (n=554) for placebo plus ADT (p<0.001). MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.1
The proven tolerability of NUBEQA was supported by the three adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo): fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.1
Secondary Endpoint Data from Phase III ARAMIS Trial Now Included in Prescribing Information
In the Phase III ARAMIS trial, men with nmCRPC receiving NUBEQA plus ADT showed a statistically significant improvement in OS compared to placebo plus ADT, with a 31% reduction in risk of death (HR=0.69, 95% CI 0.53-0.88; p=0.003). OS was statistically significant despite 31% (n=170) of patients in the ADT arm crossing over to NUBEQA. In total, 55% (n=307) of patients in the ADT arm crossed over to NUBEQA or received another life-prolonging therapy prior to this analysis.1
Other secondary endpoints incorporated in the Prescribing Information for NUBEQA also showed statistical significance, including delaying time to pain progression (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).1
Time to pain progression was defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids and reported in 28% of all patients on study.1
There was no safety update of the Prescribing Information, reflecting no new safety signals discovered at the final analysis. The Prescribing Information was updated to include additional drug interactions. NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.1
References:
- NUBEQA® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021
- Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020.
Source: WIRE, B., 2021. U.S. FDA Approves Addition Of Overall Survival And Other Secondary Endpoint Data To NUBEQA® (Darolutamide) Prescribing Information. [online] Businesswire.com.
Related Content:
Overall Survival Data from the Global, Phase 3 ARAMIS Trial in Men with Non Metastatic Castration-Resistant Prostate Cancer (nmCRPC) - Karim Fizazi
Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide