Promising phase 3 results for the Xtandi combo in prostate cancer
Astellas Pharma Inc. and Pfizer Inc. have announced the trial results of a phase 3 study in prostate cancer.
The results showed XTANDI (enzalutamide) plus leuprolide significantly reduced the risk of metastases or death by 58% compared to placebo plus leuprolide, as assessed by the primary endpoint of metastasis-free survival (MFS) in men with non-metastatic hormone sensitive prostate cancer (nmHSPC; also known as non-metastatic castration-sensitive prostate cancer (nmCSPC) with high risk of biochemical recurrence (BCR).
These data are from the phase 3 EMBARK trial, which evaluated patients across three study arms (XTANDI plus leuprolide, placebo plus leuprolide, or XTANDI monotherapy), presented as a plenary session during American Urological Association annual meeting 2023.
The overall safety profile is consistent with the known safety profiles of the individual drugs. The most common side effects in those treated with XTANDI plus leuprolide were fatigue, hot flushes, and arthralgias and in those treated with XTANDI monotherapy were fatigue, gynecomastia, and arthralgias.
“There are patients with localized prostate cancer who undergo prostatectomy or radiation therapy in an attempt to cure their disease, but, unfortunately, some patients will develop BCR,” said Neal Shore, chief medical officer of US urology and surgical oncology, GenesisCare, director, Carolina Urologic. Research Center, and principal investigator for the Embark study.
“Importantly, some patients with BCR are at very high risk of developing metastatic disease, which may warrant a course of therapeutic intervention. The clinical goal of BCR therapy is to delay cancer progression and avoid metastatic disease. The MFS results from the Embark study demonstrated that this intervention with XTANDI plus leuprolide was statistically significant for patients with high-risk BCR.”
“The EMBARK study is a phase 3 trial exploring the potential of enzalutamide in patients with non-metastatic hormone sensitive prostate cancer with high risk of BCR,” said Stephen J. Freedland, director of the Center for Integrated Research in Cancer and Lifestyle and Chair of the Warschaw Robertson Family Law in a statement. Prostate Cancer at Cedars-Sinai Cancer and clinical trial principal investigators.
“If approved, we hope to provide men with new options earlier in the course of their disease.”
Consistent with the study’s primary endpoint, statistically significant and clinically significant improvement was also observed in the main secondary endpoint of the trial in the XTANDI combination and monotherapy groups.
Specifically, the XTANDI monotherapy group demonstrated that treatment with XTANDI reduced the risk of metastasis or death by 37% compared to leuprolide plus placebo, meeting the MFS endpoint. Treatment with XTANDI plus leuprolide and XTANDI monotherapy reduced the risk of developing PSA by 93% and 67%, respectively, compared with placebo plus leuprolide. The risk of progression in starting a new antineoplastic therapy was reduced by 64% in those treated with XTANDI plus leuprolide and 46% in those treated with XTANDI monotherapy versus placebo plus leuprolide.
Positive trends in the primary secondary endpoint of overall survival (OS) were also observed in the XTANDI combination arm at the time of analysis, but these data are immature. Patients in the trial will be followed for the next final OS analysis.
Detailed results from the trials will be submitted for peer-reviewed publication. In addition, Embark data will be discussed with regulatory authorities, including the US Food and Drug Administration (FDA), to support potential regulatory filings for XTANDI in this indication in 2023.
XTANDI (enzalutamide) is an androgen receptor signaling inhibitor. XTANDI has received regulatory approval in one or more countries worldwide for use in men with metastatic hormone sensitive prostate cancer (mHSPC), metastatic castration resistant prostate cancer (mCRPC), and non-metastatic castration resistant prostate cancer (nmCRPC). XTANDI is currently approved for one or more of these indications in more than 100 countries, including in the US, European Union and Japan. One million patients have been treated with XTANDI globally.