Post-abiraterone enzalutamide use viable in some men

San Francisco-Although the activity of enzalutamide (XTANDI) is blunted in patients with metastatic castration-resistant prostate cancer (mCRPC) who have been treated previously with abiraterone acetate (ZYTIGA), a meaningful number of these patients still experience a decline in PSA level with enzalutamide, according to a recent study.

The retrospective analysis of 195 patients with mCRPC treated with enzalutamide at seven academic medical centers showed more than one-third who received prior abiraterone achieved a ≥30% decline in PSA level.

The efficacy of sequencing hormonal agents in the treatment of mCRPC is not well understood. Modest responses of brief duration have been observed in small retrospective analyses of sequencing enzalutamide after abiraterone or abiraterone after enzalutamide in the post-docetaxel (Taxotere) setting, said first author Heather Cheng, MD, PhD, a hematology and oncology fellow at Fred Hutchinson Cancer Research Center in Seattle. She presented the findings at the Genitourinary Cancers Symposium in San Francisco.

Dr. Cheng and colleagues used logistic regression to evaluate the association between declines in PSA level on enzalutamide following abiraterone in abiraterone responders and non-responders.

Seventy-nine percent of the patients received prior chemotherapy and 81% received prior abiraterone. Median patient age was 70 years; 88% had bone metastases.

Of the 195 patients, 183 were evaluable for PSA response (33 who were abiraterone-naïve, 71 who received abiraterone previously and were abiraterone sensitive, and 79 who received prior abiraterone but were abiraterone resistant). Of the 183 evaluable, 42% of all patients treated with enzalutamide achieved a ≥30% PSA decline on enzalutamide. Of the 150 patients who received prior abiraterone and were evaluable for PSA response, 39% (58 of 150) achieved a ≥30% PSA decline on enzalutamide.

Similar response rates to enzalutamide were observed regardless of prior docetaxel history or steroid use at initiation of enzalutamide.

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“About 30% of patients who did not respond to abiraterone did respond to enzalutamide, so there are overlapping but also some distinct mechanisms of resistance,” said Dr. Cheng, who worked on the study with Evan Y. Yu, MD, and co-authors.

“Until we understand the mechanisms of resistance, we won’t be able to say on a patient-by-patient basis which agent should be given first or predict how an individual patient will respond.”

Studies may help guide sequence strategies

Studies to understand molecular resistance mechanisms are in progress to help guide sequence strategies. Until the results of these studies are available, Dr. Cheng and her co-authors’ data suggest that trying enzalutamide after abiraterone is reasonable in men with mCRPC.

“We will learn more about the mechanisms of resistance in the near future through ongoing studies in the field, but until then, if you’ve had abiraterone and did not have a PSA decline, there’s still a possibility that enzalutamide can help control your prostate cancer,” she said.

Dr. Yu and several study co-authors reported financial and/or other relationships with Astellas Pharma, Dendreon, Janssen Pharmaceuticals, and/or Medivation.UT

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