Results from a randomized phase II study presented Saturday at the American Society of Clinical Oncology (ASCO) annual meeting indicates there might be a new drug on the horizon for men with advanced prostate cancer. OncoGenex Pharmaceuticals drug known as OGX-011 extended the survival of patients with advanced prostate cancer by almost seven months in a small phase II study.
The phase II study enrolled 82 men with advanced prostate cancer who had not yet begun chemotherapy treatment. The patients were randomized to receive either a combination of OGX-011 plus Taxotere or Taxotere alone.
The median overall survival for the men treated with OGX-011 plus Taxotere was 23.8 months compared to 16.9 months for men treated with Taxotere alone — an improvement in survival of 6.9 months favoring the experimental arm of the study. In this study, treatment with OGX-011 reduced the risk of death by 39% compared to treatment with Taxotere alone.
Being a phase II study wasn’t designed to prove the drug’s ability to prolong survival, its goal was to evaluate toxicity and dosing. Even though the survival benefit seen in the OGX-011 study was not statistically significant we should remember that Taxotere was approved in 2004 based on a 2.4-month survival advantage in advanced prostate cancer. If a phase III trial is conducted a similar results are demonstrated, the FDA is bound to experience a political football not different from the issues surrounding the initial FDA evaluation of Provenge.
OGX-011 prolonged survival despite having little or no measurable effect on tumor progression compared to Taxotere alone. Fifty-eight percent of men treated in the OGX-011 arm reported a PSA response compared to 54% of men in the Taxotere-alone arm.
Progression-free survival was 7.3 months for the OGX-011-treated men compared to 6.1 months for the men treated with Taxotere alone, also nor a statistically significant difference.
The median number of treatment cycles administered was also greater in the OGX-011 arm (nine cycles) compared to seven cycles for men in the Taxotere arm of the study.
OncoGenex will now have to seek a partner and/or raise cash from a stock offering in order to pay for phase III studies. to confirm the drug’s efficacy and safety in larger phase III studies before seeking regulatory approval from the FDA.
OncoGenex is working with the U.S. Food and Drug Administration to finalize plans for two, phase III studies. The first would be a repeat of the current phase II study in first-line metastatic prostate cancer patients, upsized to enroll about 800 patients with overall survival as the primary endpoint.
The second phase III study would be in second-line prostate cancer patients with pain palliation as the primary endpoint.
OGX-011 is designed to inhibit a protein known as clusterin that plays a role in cell survival. By knocking out clusterin in tumors, OGX-011 makes cancer cells more vulnerable to chemotherapy and other tumor-killing drugs.
OncoGenex is also testing OGX-011 in other types of cancer, including lung and breast.
The major difference today between OGX-011 and Dendreon’s(DNDN Quote) prostate cancer vaccine Provenge is that OGX-011 is being used in combination with Taxotere while Provenge is administered to men with prostate cancer who have not yet been treated with Taxotere.
Joel T Nowak MA, MSW