Trial Shows XTANDI Significantly Improved Radiographic PFS in Metastatic Hormone-Sensitive Prostate Cancer

Pfizer and Astellas Pharma announced results from the Phase 3 ARCHES trial in men with metastatic hormone-sensitive prostate cancer (mHSPC). Prostate cancer is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body. Men are considered hormone (or castration) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels.

The results show that XTANDI (enzalutamide) plus androgen deprivation therapy (ADT) met the primary endpoint by significantly reducing the risk of radiographic progression or death by 61% versus ADT alone (n=1,150; HR=0.39 [95% CI: 0.30-0.50]; p<0.0001).

"The ARCHES trial demonstrated that XTANDI plus standard hormonal therapy delayed disease progression, and if approved, has the potential to be an important treatment option for men with prostate cancer that has spread but has not yet become hormone resistant," said Andrew Armstrong, M.D., Professor of Medicine, Surgery, Pharmacology and Cancer Biology, and Director of Research in the Duke Cancer Institute’s Center for Prostate and Urologic Cancers.

Median time to a radiographic progression-free survival (rPFS) event was not reached in the XTANDI plus ADT arm, while median time to an rPFS event in the ADT alone arm was 19.4 months. Significant improvements in rPFS were also observed in all prespecified subgroups including disease volume, pattern of disease localization at baseline, geographic region, and prior docetaxel use (HRs=0.24-0.53). Secondary endpoints reported in the abstract showed that XTANDI plus ADT reduced the risk of PSA progression (HR=0.19 [95% CI: 0.13-0.26]; p<0.0001) and reduced the risk of starting a new antineoplastic therapy (HR=0.28 [95% CI: 0.20-0.40]; p<0.0001) compared to ADT alone. Undetectable PSA and objective response rates were also higher in men treated with XTANDI plus ADT versus ADT alone (68.1% versus 17.6%; p<0.0001 and 83.1% versus 63.7%; p<0.0001, respectively). Treatment with XTANDI plus ADT did not significantly reduce the risk of deterioration in urinary symptoms compared to ADT alone. At the time of the analysis, overall survival (OS) data were not mature.

Adverse events (AEs) in the ARCHES clinical trial were generally consistent with those reported in enzalutamide clinical trials in patients with castration-resistant prostate cancer (CRPC). Grade 3 or 4 AEs were reported in 23.6 percent of men receiving XTANDI plus ADT versus 24.7 percent of men receiving ADT alone. Common AEs (occurring in at least 5 percent of patients) that were reported more often in patients treated with XTANDI plus ADT versus those treated with ADT alone included hot flush, fatigue, arthralgia, hypertension, nausea, musculoskeletal pain, diarrhea, asthenia and dizziness.

Based on the ARCHES results, the companies intend to discuss these data with global health authorities to potentially support a new indication for XTANDI in men with mHSPC. XTANDI is currently approved in the U.S. and Japan for the treatment of CRPC and in the EU for the treatment of metastatic and high-risk non-metastatic CRPC.

The Phase 3, randomized, double-blind, placebo-controlled, multi-national trial enrolled 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) at sites in the United States, Canada, Europe, South America and the Asia-Pacific region. Patients in the ARCHES trial were randomized to receive XTANDI 160 mg daily or placebo and continued on a luteinizing hormone-releasing hormone (LHRH) agonist or antagonist or had a history of bilateral orchiectomy. The ARCHES trial included patients with both low- and high-volume disease and both newly diagnosed patients with mHSPC and patients who had prior definitive therapy and subsequently developed metastatic disease. The trial also included some patients who had received recent treatment with docetaxel for mHSPC, but whose disease had not progressed. The primary endpoint of the trial was radiographic progression-free survival (rPFS), defined as the time from randomization to the first objective evidence of radiographic disease progression as assessed by central review, or death within 24 weeks of treatment discontinuation.

In men with prostate cancer, the disease is considered metastatic once the cancer has spread outside of the prostate gland to other parts of the body, such as the bones, lymph nodes, bladder and rectum. Men are considered hormone (or castration) sensitive if their disease still responds to medical or surgical treatment to lower testosterone levels. Approximately 38,000 men in the U.S. develop metastatic HSPC every year.

XTANDI (enzalutamide) is an androgen receptor inhibitor indicated for the treatment of patients with castration-resistant prostate cancer.

As part of Pfizer and Astellas’ ongoing commitment to the clinical development of enzalutamide, XTANDI is also being evaluated in the EMBARK trial, in men with high-risk non-metastatic HSPC.

Register as Visitor to CPhI China 2019!

-----------------------------------------------------------------------
Editor's Note:

To apply for becoming a contributor of En-CPhI.cn,

welcome to send your CV and sample works to us,

Email: Julia.Zhang@ubmsinoexpo.com.