Treating Aggressive Prostate Cancer with Maha Hussain, MD

Episode Summary

More than one million men are diagnosed with prostate cancer worldwide every year. More than 350,000 will die from the disease. For those with advanced metastatic prostate cancer, treatments are limited. But a new phase 3 international clinical trial shows that a genetic-based therapy could offer new hope for patients with specific gene mutations in their tumors. Maha Hussain, MD, led the trial and presented results at the Presidential Symposium at the 2019 European Society of Medical Oncology in Barcelona.

The trial preselected patients who have genetic alterations that enable cells to repair themselves from damage. Those most commonly known are the BRACA 1, BRACA 2 and ATM genes, but there are several others. Patients were randomly assigned to receive olaparib, which has been used in other cancers (ovarian, breast and pancreatic) with similar alterations – or standard hormone therapy with either abiraterone and prednisone or enzalutamide.

Maha Hussain: "In this case, the primary cohort met its planned target and there was a doubling of the time to disease progression with a median of over seven and a half months, roughly. And that actually translated into a 66 percent reduction in the risk of death or progression in favor of the olaparib treatment by comparison to the patients who received standard of care therapy."

The results are the first to show the potential of a genetically targeted treatment for patients with advanced prostate disease. The benefit was observed across the board, irrespective of the patient’s cancer location, prior treatment, where the cancer had spread (bone, liver or lymph nodes), the patient’s PSA (prostate-specific antigen) or age.

Maha Hussain: "These are clinical features that would predict for prognosis for that patient. So for example, a patient who has one spot or two spots on their bone is not the same as somebody who has a liver loaded with cancer. Someone who has a PSA of five is different than someone, potentially, with a PSA of 200. And the reason is it reflects the bulk of the cancer, the aggressiveness, the biology. Now, these are not very specific metrics, but they have been very prognostic and associated with outcomes."

The major reported side effect was anemia. There was also an incidental finding of pulmonary embolism that was seen in about 4 percent of the patients -- more so in the olaparib-treated patients compared to the control arm.

Maha Hussain: "However, this is not a side effect that has been previously reported with olaparib, which is widely used in breast and ovarian cancer at this moment. Whether this is something that is accidental versus related to treatment is really not clear. This is something that (will be) looked into in more detail. The good news is none of these were fatal and all of the patients that had the blood clots in their lungs continued on treatment."

The results from the trial will soon be published and then the next step is FDA approval for use of olaparib as a genetically targeted treatment for patients with advanced disease

Maha Hussain: "If it gets FDA-approved (olaparib) will be the first targeted agent that has been pre-approved in a molecular preselected patient population. And I think that opens up the door, not only specifically this class of drugs, but I think opens up the door for more targeted therapy in prostate cancer."

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Recorded on October 4, 2019.

This podcast episode is not eligible for AMA PRA Category 1 Credit(s)™.