Early chemo-ADT combination may be new PCa standard

A new study showing a survival benefit of more than 1 year with a chemotherapy-hormonal therapy combination given prior to castration resistance is being hailed by the study’s first author as a “new standard” of treatment for certain men with metastatic, hormone-sensitive prostate cancer.

Other experts in prostate cancer are calling the study findings a “home run” and potentially practice changing.

The study, from Dana-Farber Cancer Institute in Boston and the Eastern Cooperative Oncology Group, was presented on Sunday at the American Society of Clinical Oncology annual meeting in Chicago.

“This is the first study to identify a strategy that prolongs survival in newly diagnosed, metastatic prostate cancer,” said Christopher J. Sweeney, MBBS, of Dana-Farber’s Lank Center for Genitourinary Oncology.

“The benefit is substantial and warrants this being a new standard treatment for men who have high-extent disease and are fit for chemotherapy,” added Dr. Sweeney, principal investigator of the E3805 National Cancer Institute-funded study.

The trial tested the hypothesis that immediately treating metastatic, castration-resistant prostate cancer (mCRPC) with chemotherapy in addition to androgen deprivation therapy (ADT) would impair the tumor cells’ ability to repair damage, delaying the development of resistance.

A total of 790 men newly diagnosed with metastatic disease were enrolled and were randomized to receive ADT alone or ADT with docetaxel (Taxotere) over 18 weeks. In the ADT-only group, 124 patients were given docetaxel when their cancer worsened. In the ADT-plus-docetaxel group, 45 patients whose disease progressed received additional docetaxel.

At a median follow-up of 29 months, 136 patients in the ADT-only group had died versus 101 in the group that received both drugs. This translated into a median overall survival of 57.6 months for men who received early chemotherapy compared with 44 months in the group given ADT as the only initial treatment- more than a year of additional life, according to a Dana-Farber statement.

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In the 520 patients who had high-extent disease, treatment with ADT plus docetaxel had a greater benefit: median overall survival of 49.2 months versus 32.2 in the ADT-only group, for a difference of 17 months.

The striking survival benefit associated with early use of docetaxel was most striking in men with a high burden of metastatic disease, Dr. Sweeney reported. He said more time is needed to assess the benefit of the drug combination in the men with lesser burdens of disease, as their median survival has not yet been reached.

The most serious side effects were neutropenic fever and neuropathy; one patient died as a result of treatment.

J. Brantley Thrasher, MD, of the University of Kansas Medical Center in Kansas City, called the paper "very significant."

"To me this makes a lot of sense," said Dr. Thrasher, a Urology Times editorial consultant. "Many of the solid organ tumors that we treat respond well to hitting them early with chemotherapy instead of late when the tumors have changed dramatically after hormonal therapy. More follow-up is required to find out where those patients with smaller tumor burdens end up, but it certainly appears that all of these patients benefited from ADT plus docetaxel versus ADT alone.

"This could very well be a new standard but will likely require validation from further studies."

The outcome could prove to be a "real game changer, because the differences are real," Derek Raghavan, MD, PhD, of Carolinas Healthcare System's Levine Cancer Center in Charlotte, NC, told MedPage Today.

"My own view is that if you can show this to a man on the street and ask 'Is this worthwhile?' and the man on the street says 'Yeah, that's a big difference,' then you've got a home run" he said.

In an ASCO video, ASCO President Clifford A. Hudis, MD, said, “What was unexpected and I think quite surprising was that there was a very large improvement in the length of time that men lived after they got treated this way. So let’s be very clear: Frontloading their treatment with chemotherapy and hormone therapy instead of waiting resulted in improved overall survival. This was especially true in the subset of men defined as having high-volume disease.

“This has a real potential to change practice.”

Dr. Sweeney discloses consultant or advisory roles with Astellas Pharma, BIND Biosciences, Bionomics, Exelixis, Genentech, Janssen Pharmaceuticals, Roche, and Sanofi.