New Therapy for Aggressive Prostate Cancer Improves Survival

Experimental therapy has prolonged the lives of men with aggressive prostate cancer who have withstood other treatments, given new hope to patients with advanced disease, and opened the door to a promising new form of cancer therapy.

In men who received the new therapy, there was an almost 40 percent reduction in deaths over the course of the clinical trial compared to similar patients who received only standard treatment, researchers reported Wednesday.

Prostate cancer is the second leading cause of cancer death in American men after lung cancer; An estimated 34,130 men will die from prostate cancer this year. One in eight men will be diagnosed with the disease at some point in their life. The risk increases with age, and the cancer is more common in black men.

The new treatment relies on a radioactive molecule that targets a protein on the surface of prostate cancer cells. The study, which followed 831 patients with advanced disease in 10 countries over a median of 20 months, was published in the New England Journal of Medicine.

“This is something new – you’re driving the radiation straight to the cancer itself,” said Karen Knudsen, president and executive director of the American Cancer Society. “It’s a much more sophisticated strategy to fight the tumor.”

“You don’t just destroy the cancer cells – you intelligently bomb the place the tumor found for itself.”

There is no definitive cure for metastatic prostate cancer and there is an urgent need for new therapies, said Dr. Knudsen. Most life-prolonging treatments are based on suppressing or blocking androgens, the male hormones that fuel prostate cancer.

“This opens the door for precise radiation therapy that targets other molecules that are on the surface of other cancer cells,” said Dr. Philip Kantoff, chairman of medicine at Memorial Sloan Kettering Cancer Center in New York.

The test treatment called Lutetium-177-PSMA-617 combines a compound that targets a protein on the surface of prostate cancer cells called prostate-specific membrane antigen, or PSMA, with a radioactive particle that attacks the cells.

The PSMA protein, which can be detected by imaging scans, is almost entirely on prostate cancer cells, so the treatment does less damage to surrounding tissues, said Dr. Oliver Sartor, co-lead researcher on the study and medical director of the Tulane Cancer Center in New Orleans.

Although the protein is not ubiquitous in prostate tumors, it is found more than 80 percent of the time. Of the patients examined for the study, 87 percent were PSMA-positive. Only the men who were positive for the marker were included in the study.

The study enrolled men with a form of metastatic prostate cancer called castration-resistant prostate cancer. All patients had a disease that progressed despite treatments with chemotherapy and hormone therapy to suppress and block androgens.

Participants were randomly assigned to receive the experimental treatment, which was administered in up to six doses every six weeks with standard treatment, or to continue standard treatment alone, but without chemotherapy or other isotopes.

After a median follow-up of 20.9 months, patients who received the experimental treatment survived a median of 15.3 months, compared with 11.3 months for those who received standard care only, a reduction of 38 percent.

Her tumors were more likely to shrink, their prostate-specific antigen levels were more likely to drop, and the risk of their cancer progressing was reduced by 60 percent.

Side effects – most commonly fatigue, dry mouth, and nausea – were more common in those who received the compound than those who didn’t, but didn’t seem to affect quality of life significantly, the researchers said.

The study had some limitations. It was a randomized study, but because of the difficulty of doing a double-blind study of radioactive treatment, the study was open-ended: both patients and doctors knew whether they were receiving the treatment or not. This led to problems early on, as patients who were disappointed with their assignment withdrew from the study.

The investigational drug worked where other approaches would have failed, emphasized Dr. Sartor. “These patients had received essentially all of the therapies available,” he said. “This is the first drug that targets the tumor and actually results in an overall survival benefit in incredibly pre-treated patients.”

Dr. Sartor was together with Dr. Bernd Krause from the Rostock University Hospital in Germany co-director of the study. The study was sponsored by Endocyte Inc. and Advanced Accelerator Applications, which are Novartis companies; Dr. Sartor is a paid advisor to the company. The data was analyzed by the sponsor and made available to the authors in confidence.

Novartis officials said the company will apply to the Food and Drug Administration for approval of the new treatment later this year.

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