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Prostate cancer disrupted

Why the treatment paradigm for prostate cancer could soon see a shake-up

Two imminent disruptions threaten to upend the treatment landscape for prostate cancer, changing who gets anti-androgen therapies and ushering in the first new MOAs in decades.

The launch of generic abiraterone means next generation anti-androgens in development will likely be pushed into earlier settings than the late-stage disease Johnson & Johnson’s branded Zytiga abiraterone has traditionally treated.

On the other hand, new mechanisms are entering the scene. And given the resistance likely to develop to the anti-androgens, the new MOA compounds may be able to step straight into a treatment void in late disease settings.

Reduced androgen signaling has been the major goal of prostate cancer treatment for over sixty years, first via surgical or chemical castration, then through targeted therapies. The reason is that almost all prostate cancers are heavily dependent on androgen receptor activation and only become independent late in disease, after anti-androgen therapy.

But where modern anti-androgens slot into the treatment paradigm could rapidly change due to the launch of generic forms of Zytiga, which has been one of the most successful next-generation prostate cancer drugs. Its 2018 sales were $3.5 billion.

Zytiga and its closest competitor Xtandi enzalutamide from Pfizer Inc. and Astellas Pharma Inc. were initially approved in metastatic castration-resistant prostate cancer (mCRPC). However, data presented over the past several years -- most recently at the American Society of Clinical Oncology 2019 Genitourinary Cancers Symposium (ASCO GU) -- have demonstrated that the anti-androgen class is equally effective in two earlier disease settings, non-metastatic CRPC and metastatic hormone-sensitive prostate cancer (mHSPC) (see Figure: “Treatment Continuum”).

According to three physicians who spoke to BioCentury, the efficacy of anti-androgens and the lack of differentiation between them means generic abiraterone may eventually dominate in these earlier prostate cancer settings.

“I’m thinking that the generic abiraterone, if it gets cheap enough, is really a disrupter,” A. Oliver Sartor, professor of medicine at Tulane University and medical director of Tulane Cancer Center, told BioCentury.

“Generic abiraterone, if it gets cheap enough, is really a disrupter.”

A. Oliver Sartor, Tulane University


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