新しいクラスの薬剤は進行前立腺がん患者において有効である(Abstract 5006)

First results of a phase III international clinical study called TITAN, which evaluated the effectiveness and safety of a new drug, apalutamide, to treat metastatic castration-sensitive prostate cancer were presented at the 2019 American Society of Clinical Oncology Annual Meeting. Researchers found that treatment with apalutamide significantly improved overall survival, with a 33% reduction in risk of death compared to standard-of-care therapy (P=0.0053). Additionally, this study showed apalutamide significantly delayed radiographic disease progression (P<0.0001) and time to initiation of chemotherapy was improved (P<0.0001). 

The study was published in the New England Journal of Medicine at the time of presentation.

The study was led by Kim Chi, MD, medical oncologist with the British Columbia Cancer Agency and associate director of clinical research at the Vancouver Prostate Centre in Canada. Neeraj Agarwal, MD, a prostate cancer physician-scientist at Huntsman Cancer Institute (HCI) and professor of medicine at the University of Utah (U of U), was member of the international steering committee for the trial and the second author on the publication. The trial included participation of 230 institutions worldwide and enrollment of more than 1,000 patients on the trial.

According to Chi, "This is a major study that showed, for the first time, significantly improved overall survival and delay of disease progression with this novel class of drugs known as 'potent and direct androgen receptor inhibitor' in men with advanced prostate cancer." Chi and Agarwal believe the results of this study may change the way a vast majority of men with advanced prostate cancers are treated.

This study was built upon prior evaluations of apalutamide.  The aim was to conduct a large-scale assessment of apalutamide when used in combination with the standard-of-care treatment for men with prostate tumors that have metastasized. Apalutamide belongs to a class of drugs that inhibit the normal function of androgens like testosterone. These drugs act by blocking androgen receptors.

Prostate cancer is the second leading cause of cancer death in men. While survival is nearly 100% for men with early stage prostate cancers, the five-year survival rate for men with prostate tumors that have metastasized is only 30%, according to the American Cancer Society. Men with advanced forms of prostate cancer are typically treated with drugs that work to significantly lower testosterone levels, which slows disease progression. This study evaluated the combination of apalutamide plus the testosterone-reducing drugs.

Agarwal worked with colleagues from five continents to coordinate the sophisticated scientific review necessary to evaluate study results. Patients who received apalutamide plus standard-of-care therapy had significantly improved outcomes versus patients who only received the testosterone-reducing drug. After reviewing the early results, an independent data monitoring committee recommended that all participants in the study receive apalutamide plus the standard treatment.

Before apalutamide, other strategies to improve the survival rates for prostate cancer patients included chemotherapy and abiraterone, a drug that blocks testosterone production by prostate cancer cells, alongside long-term treatment including steroids. "With the potential approval and availability of apalutamide, we may have an option that will allow us to avoid the side effects of chemotherapy and long-term steroid use in our patients with advanced prostate cancer," said Agarwal.

This research was supported by the National Cancer Institute and by Huntsman Cancer Foundation. The study was sponsored by Aragon Pharmaceuticals and Janssen Research & Development, LLC.