Darolutamide Plus Androgen Deprivation Therapy Showed Significant Improvement in Overall Survival with Proven Efficacy and Tolerability in Men with Non-Metastatic Castration-Resistant Prostate Cancer

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 ADT, compared to 18.4 months (n=554) for placebo plus ADT (p<0.001); however OS data were not yet mature at the time of the MFS analysis.² 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. Adverse reactions occurring more frequently in the NUBEQA arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).² NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.²

“Men with nmCRPC typically do not have cancer symptoms. In selecting a treatment for these patients, my goal as a clinician is to improve their overall survival while limiting side effects and drug interactions,” said Karim Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, Villejuif, France. “These data add to the growing evidence for darolutamide as an effective treatment option with proven tolerability that extends patients’ lives and delays cancer symptoms.”

Final OS Analysis Presented at ASCO Virtual Scientific Program

Men receiving NUBEQA plus ADT showed a statistically significant improvement in the secondary endpoint of OS compared to ADT alone, with a 31 percent reduction in risk of death (HR=0.69, 95% CI 0.53-0.88; p=0.003).¹ 

With extended follow-up, any grade treatment-emergent adverse events (AEs) at final analysis were generally consistent with the primary analysis of the Phase III ARAMIS trial.^1,2 Previously, in the primary analysis, any grade AEs occurred in 83.2 percent who received NUBEQA plus ADT and 76.9 percent who received ADT alone.² Grade 3 or 4 AEs occurred in 24.7 percent who received NUBEQA plus ADT and 19.5 percent who received ADT alone.² Grade 5 AEs occurred in 3.9 percent who received NUBEQA plus ADT and 3.2 percent who received ADT alone.² Serious AEs occurred in 24.8 percent receiving NUBEQA plus ADT and in 20.0 percent receiving ADT alone.² The percentage who discontinued the trial regimen because of AEs was 8.9 percent in the NUBEQA plus ADT group and 8.7 percent in the ADT group.²

Previously, OS data were not mature at the time of MFS analysis (57 percent of the required number of events).² Secondary endpoints were evaluated in a hierarchical order, with a significance level of 0.05 split between the primary analysis and final analysis (planned to occur after 240 deaths from any cause) of secondary endpoints.^1,2 The endpoint OS was used to determine the alpha spend and significance threshold for each of the secondary endpoints.² Given the OS analysis did not meet the threshold for statistical significance, this prevented all of the secondary endpoints from meeting the criteria for statistical significance at the interim analysis.²

In the follow-up analysis of the same secondary endpoints, all were statistically significant.¹ NUBEQA plus ADT showed statistical significance in delaying time to pain progression (HR=0.65, 95% CI 0.53-0.79; p<0.001), time to first initiation of treatment with cytotoxic chemotherapy (HR=0.58, 95% CI 0.44-0.76; p<0.001) and time to first symptomatic skeletal event (SSE) (HR=0.48, 95% CI 0.29-0.82; p=0.005) versus ADT alone.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, in patients treated with NUBEQA as compared to ADT alone. Pain progression was reported in 28 percent of all patients at the interim analysis.

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

^© 2020 Bayer 
BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer.

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References:

1. Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Overall survival (OS) results of phase III ARAMIS study of darolutamide (DARO) added to androgen deprivation therapy (ADT) for nonmetastatic castration-resistant prostate cancer (nmCRPC). American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program; May 2020. Abstract 5514
2. Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2019.