Apparent Bone Lesions Not Tied to Enzalutamide Failure in Prostate Cancer

By David Douglas

December 26, 2019

NEW YORK (Reuters Health) - In certain men with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with enzalutamide, unconfirmed lesions detected on follow-up bone scans may not be bode ill, according to a secondary analysis of phase 3 clinical trials.

As Dr. Andrew J. Armstrong told Reuters Health by email, "A major clinical challenge in prostate cancer treatment has been to determine how bone metastases are responding, as this is a common pattern of spread. Here we show that new bone lesions in some men with hormone resistant prostate cancer can be seen during clinical responses to enzalutamide, a newer and more potent form of hormonal therapy."

He continued, "These new lesions in many patients are a form of false progression particularly in earlier disease settings, which have been called bone scan flare, and patients with these new bone lesions have a similar survival and quality of life as responding patients."

As reported in JAMA Oncology, Dr. Armstrong of Duke University, Durham, North Carolina and colleagues reviewed data from two studies on enzalutamide-treated participants with a decrease in prostate-specific antigen level at any time or with stable disease or soft-tissue disease responding to treatment based on radiologic findings.

In the first study (PREVAIL) involving 643 chemotherapy-naive men, early and late unconfirmed lesions were seen in 177 patients (27.5%) with stable disease or disease responding to enzalutamide. Median radiographic progression-free survival and median overall survival was similar to men without such new lesions.

"These reassuring findings," Dr. Armstrong pointed out, "suggest that treatment should not be stopped in this setting if a patient is otherwise doing well."

However, in the second study (AFFIRM) of 404 men who had previously received docetaxel, such lesions were seen in 73 men (18.1%) with comparable responses. Although median radiographic progression-free survival was not reduced in this group, median overall survival was (hazard ratio, 1.94).

In email to Reuters Health, Dr. Neeraj Agarwal of the University of Utah, Salt Lake City, co-author of an accompanying editorial, said the investigators "showed that continuing enzalutamide in post-docetaxel mCRPC patients with new unconfirmed bone lesions does not provide survival benefit. The current standard is to repeat the bone scan to confirm these lesions after 6-12 weeks which likely exposes our patients to financial and treatment-related toxicities, while delaying other beneficial therapies."

Dr. Agarwal added, "These findings suggest the need for a more precise assessment of bone metastasis. Some of these approaches include better quantitation of bone metastasis burden with automated bone scan index or emerging imaging approaches such as whole whole-body magnetic resonance imaging and positron emission tomography (PET) using radiopharmaceuticals such as choline, fluciclovine, and prostate-specific membrane antigen (PSMA) PET.

"It is time," he concluded, "that these new modalities are incorporated into prospective clinical trials to evaluate bone metastasis burden, which will eventually lead to a more accurate response assessment of novel therapeutic approaches."

SOURCE: and JAMA Oncology, online December 11, 2019.