Body composition unchanged after advanced prostate cancer treatment

Villejuif, France-No differences in body composition were found among metastatic castration-resistant prostate cancer (mCRPC) patients taking abiraterone acetate (ZYTIGA), enzalutamide (Xtandi), or placebo who were treated as part of two clinical trials.

The finding is important because these agents are being considered for use earlier in the course of prostate cancer, which would mean a longer duration of treatment, thus possibly affecting cardiovascular risk, said first author Ecaterina Ileana, MD, who presented the study at the American Society of Clinical Oncology annual meeting in Chicago.

Abiraterone and enzalutamide have each been shown to improve survival in patients with mCRPC that progresses after therapy with docetaxel (Taxotere). Both drugs are androgen receptor-directed compounds, but they work via different mechanisms. Enzalutamide works within the tumor cell to target multiple steps in the androgen receptor pathway, thereby preventing the growth-promoting effects of androgens on the tumor cell. Abiraterone reduces androgen production by blocking the CYP17 enzyme, by which it inhibits androgen production at three sources: the testes, adrenal glands, and prostate tumor tissue.

Patients treated at Institut Gustave Roussy, Villejuif, France, as part of the AFFIRM and COU-AA-301 clinical trials were included in this analysis, said Dr. Ileana, a fellow in the department of medical oncology at Institut Gustave Roussy. There were 90 patients included as part of AFFIRM (62 treated with enzalutamide and 28 with placebo) and 37 as part of COU-AA-301 (24 treated with abiraterone plus prednisone and 13 with placebo plus prednisone).

Cross-sectional areas of visceral adipose tissue, subcutaneous adipose tissue, and skeletal muscle were assessed by computed tomography imaging at the third lumbar vertebra and were indexed for height at baseline and 3, 6, and 12 months of treatment. The data from patients treated with abiraterone or enzalutamide were compared with that of placebo recipients. Tissue changes were compared to baseline.

At inclusion, 74 patients (58%) were overweight or obese (body mass index >24.9 kg/m²) and only two patients were underweight (BMI <18.5 kg/m²). Ninety-seven patients (81%) were sarcopenic; 75% of the overweight or obese patients were sarcopenic.

Muscle loss ‘not significant’

“At 3 months, we found that all of the patients were losing muscle and gaining visceral adipose tissue, but the changes were not significant,” said Dr. Ileana.

Overall, patients lost a mean of 4.5% of muscle mass (0.7 kg of muscle) at 3 months, which was significant (p=.01). A mean loss in subcutaneous adipose tissue of 4.6% and a mean increase of visceral adipose tissue of 10.7% were nonsignificant. A similar pattern was observed at 6 months.

At 3 months, patients treated with enzalutamide had a significant loss of muscle mass from baseline (mean: 3.7%) but not significantly different from placebo. Enzalutamide-treated patients had a nonsignificant decrease from baseline in subcutaneous adipose tissue (mean: 4.4%) and a nonsignificant increase in visceral adipose tissue (mean: 4.8%), neither of which was significantly different from changes in the placebo group.

In the COU-AA-301 study, patients treated with abiraterone lost a mean of 6.7% of muscle mass, lost a mean of 6.2% of subcutaneous adipose tissue (nonsignificant), and gained a mean of 9.2% of visceral adipose tissue (nonsignificant) compared with baseline, with no significant difference in changes compared with placebo.

“Sarcopenia is highly prevalent in patients with advanced castration-resistant prostate cancer,” Dr. Ileana said. “Now that both enzalutamide and abiraterone are available, we should be able to perform studies looking at changes over the longer term.”UT

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