Asco-GU – Unexpected backing for docetaxel

At a time of rising payer concern about the price of new drugs, even in oncology, data showing that a generic can significantly extend survival has commercial implications. This could be the upshot of Stampede, a large academic consortium-sponsored trial in hormone-responsive prostate cancer (HRPC), which showed that earlier use of docetaxel conferred a significant 10-month survival advantage.

While this was hailed as practice changing, the concern was that without a commercial champion the venerable chemotherapy might not move from its current use late in the disease. Seven months on, though, the University of Warwick's Professor Nicholas James, who presented these data at Asco and is Stampede's principal investigator, is pleasantly surprised that this idea is gaining momentum.

Speaking to EP Vantage at the Asco-Genitourinary symposium he said that, contrary to expectations, docetaxel had been recommended for use in hormone-responsive patients by various National Health Service bodies in the UK and had been adopted in some international practice guidelines.

Docetaxel has for many years been the standard for prostate cancer patients who have failed on anti-androgen therapy and are thus deemed castration-resistant. There it remained unchallenged, until the advent of the super-hormonal agents, including Johnson & Johnson's Zytiga and Astellas Pharma and Medivation's Xtandi.

These newer agents tended to relegate it to even later use in the course of the disease, and older patients often decided to forgo chemotherapy altogether on quality of life grounds. Against this background, Professor James thought it might prove difficult to shift clinical practice, even though a generic would be favoured on cost grounds. 

Remarkable success

Nevertheless, the docetaxel finding in Stampede seems to have been a remarkable success. The study is a “trial platform” that allows parallel evaluation of one or more agents on top of standard of care for HRPC of androgen deprivation therapy/radiotherapy. The trial remains ongoing, with data readouts from other cohorts, including Zytiga and Xtandi, both alone and in combination, due in 2017 and beyond.

New agents can be added to those being studied. Next up will be metformin, based on findings that glucose metabolism might be significant in this cancer indication. Importantly, each arm has a contemporaneous control, so outcomes cannot be biased by improvements in standard of care or new agents introduced over time.

One problem that Professor James can foresee is the Zytiga or Xtandi arms in Stampede rendering a positive result, or presumably company-sponsored studies in the same setting doing so. At this point, it will be clear that all of these agents should be used earlier, though questions will remain over their sequencing.

Jevtana beneficiary?

EP Vantage speculated last year that if a shift to docetaxel use in HRPC did occur it could have a knock-on benefit for Sanofi’s Jevtana, which is indicated for use after docetaxel failure (Asco – Earlier taxotere use could give Jevtana new lease of life, May 30, 2015).

At the very least it should increase the proportion of patients eligible for treatment with the drug. It will be more interesting if Sanofi sees a development opportunity for Jevtana in early-stage disease. 

One company that might have a docetaxel derivative suitable for development in early stage is Bind Therapeutics. Its BIND-014 is a prostate-specific membrane antigen-targeted docetaxel nanoparticle, which seems ideally suited to development in HRPC, given the Stampede result.

Bind presented some positive early data on BIND-014 at Asco-GU, but there was no comparison with the native molecule. Moreover, the focus of its development efforts is in squamous non-small cell lung cancer, where it will, if successful, have to compete with PD-1 inhibitors. Perhaps this will change if and when BIND-014 is licensed.     

To contact the writer of this story email Robin Davison at news@epvantage.com or follow @RobinDavison2 on Twitter

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