Jason M. Broderick
Progression-free survival (PFS) was not improved when Xtandi (enzalutamide) was added to Zytiga (abiraterone acetate) and prednisone compared to Zytiga and prednisone alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who are chemotherapy-naïve and progressed on Xtandi, according to findings from the phase 4 PLATO trial.
The results of the study have not yet been released by the codevelopers of the androgen receptor inhibitor Xtandi, Astellas and Pfizer.
“While the PLATO trial did not meet its primary endpoint, it is critical that we continue to focus on addressing the unmet needs of men with metastatic CRPC, who have a poor prognosis despite treatment advances,” Mohammad Hirmand, M.D., interim chief medical officer at Medivation, Inc, which is part of Pfizer said in a statement. “We will continue to analyze these data to better understand the results with the goal of further helping these patients.”
The global, placebo-controlled, randomized, phase 4 PLATO study (NCT01995513
) compared combination therapy with Xtandi, Zytiga and prednisone with Zytiga and prednisone alone after confirmed PSA progression on single-agent Xtandi.
During the open-label period 1 of the study, 509 chemotherapy-naïve patients with mCRPC received 160 mg/day of oral Xtandi until their PSA level increased. In the blinded period 2 part of the study, eligible patients were randomized to Xtandi (160 mg/day orally) plus Zytiga (1000 mg/day) and prednisone (5 mg orally twice daily), or placebo combined with the Zytiga and prednisone at the same doses.
The primary outcome measure was PFS. Secondary endpoints included time to PSA progression, objective response rate, quality of life and safety.
“Xtandi continues to remain an important treatment option for men with metastatic CRPC and their physicians. We are committed to continuing to explore the clinical potential of Xtandi across the disease continuum,” Steven Benner, M.D., senior vice president, therapeutic area head for oncology development, Astellas, said in a statement.
The FDA initially approved Xtandi in August 2012 for use in patients with mCRPC previously treated with docetaxel and hormonal therapy. The approval was based largely on data from the phase 3 AFFIRM study in which 1,199 men with mCRPC were randomized in a 2 to 1 ratio to receive Xtandi or placebo. The median overall survival (OS) was 18.4 months with Xtandi versus 13.6 months in the control arm.
In September 2014, the FDA expanded the approval of Xtandi to include the treatment of men with chemotherapy-naïve mCRPC, based on survival data from the phase 3 PREVAIL trial.
In the phase 3 study, 1717 men with a median age of 71 years received treatment with Xtandi (872 patients) or placebo (845 patients). The median OS was 32.4 months with Xtandi versus 30.2 months with placebo. The median radiographic PFS was not yet reached in the Xtandi arm compared with 3.9 months with placebo. The overall response rate was 58.8 percent versus 5 percent, for Xtandi versus placebo, respectively.
The FDA initially approved Zytiga in 2011 as a treatment for men with mCRPC following prior docetaxel. The approval was expanded in December 2012 to include the treatment of chemotherapy-naïve men with mCRPC.