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Influence of Abiraterone and Enzalutamide on Body Composition in Patients with Metastatic Castration Resistant Prostate Cancer - Beyond the Abstract

The treatment landscape of advanced prostate cancer has changed considerably over the last years. The newer hormonal agents, abiraterone and enzalutamide, have been shown to improve the survival of men with metastatic castration-resistant prostate cancer (mCRPC)1-4 as well as in hormone-sensitive disease.5-8 Because the median time on treatment with these drugs in the hormone-sensitive setting is in the range of two to three years, their side effects are emerging as an important new focus of interest.


It has already been shown that androgen deprivation therapy in prostate cancer leads to a loss of muscle substance and gain of fat. So far, little is known concerning the effects of abiraterone and enzalutamide on body composition.

In our study, we compared the effects of the two drugs on skeletal muscle substance and subcutaneous fat tissue in a cohort of 54 mCRPC patients. Using a deep learning image-segmentation software, areas of skeletal muscle and subcutaneous fat tissue were assessed on CT scans before and after a median of 10.8 months on treatment.

We found that both drugs led to a significant loss of skeletal muscle substance which was similar for enzalutamide (mean loss 5.2%) and abiraterone (mean loss 3.0%). Subcutaneous fat tissue was not significantly altered during treatment. In a subgroup of patients treated with enzalutamide and having regular 3-monthly imaging, we could show that muscle loss occurred early on within the first three to six months of treatment.  

These findings are of importance for patients with prostate cancer as loss of skeletal muscle may have a negative impact on quality of life as it can lead to fatigue, reduced mobility, frailty, and an increase in the risk of falls which is of high clinical relevance in a population of patients frequently having multiple bone metastases.

Further validation of our findings in larger patient cohorts is warranted. Considering that the newer hormonal agents have recently been introduced also for hormone-sensitive disease, assessing the effect of the early combination of androgen deprivation plus abiraterone/enzalutamide on body composition also warrants further study, as does investigating the effect of controlled interventions such as resistance training to prevent loss of skeletal muscle mass during treatment.

We believe that in routine care, counseling of patients about side effects of abiraterone/enzalutamide should include discussions about skeletal muscle loss and encouraging them to increase their physical activity to help counteract the side effect of muscle loss.

Written by: Stefanie Fischer, MD,1 Sebastian Clements,2 Silke Gillessen, MD3

  1. Cantonal Hospital St. Gallen, Department of Medical Oncology and Haematology, Gallen, Switzerland
  2. University of Manchester, Manchester, United Kingdom
  3. Department of Medical Oncology, Istituto Oncologico della Svizzera Italiana, Bellinzona, Switzerland
References:

  1. De Bono, Johann S., Christopher J. Logothetis, Arturo Molina, Karim Fizazi, Scott North, Luis Chu, Kim N. Chi et al. "Abiraterone and increased survival in metastatic prostate cancer." New England Journal of Medicine 364, no. 21 (2011): 1995-2005.
  2. Ryan, Charles J., Matthew R. Smith, Johann S. De Bono, Arturo Molina, Christopher J. Logothetis, Paul De Souza, Karim Fizazi et al. "Abiraterone in metastatic prostate cancer without previous chemotherapy." New England Journal of Medicine 368, no. 2 (2013): 138-148.
  3. Scher, Howard I., Karim Fizazi, Fred Saad, Mary-Ellen Taplin, Cora N. Sternberg, Kurt Miller, Ronald de Wit et al. "Increased survival with enzalutamide in prostate cancer after chemotherapy." New England Journal of Medicine 367, no. 13 (2012): 1187-1197.
  4. Beer, Tomasz M., Andrew J. Armstrong, Dana E. Rathkopf, Yohann Loriot, Cora N. Sternberg, Celestia S. Higano, Peter Iversen et al. "Enzalutamide in metastatic prostate cancer before chemotherapy." New England Journal of Medicine 371, no. 5 (2014): 424-433.
  5. Fizazi, Karim, NamPhuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y. Alekseev, Mustafa Özgüroğlu et al. "Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer." New England Journal of Medicine 377, no. 4 (2017): 352-360.
  6. James, Nicholas D., Johann S. de Bono, Melissa R. Spears, Noel W. Clarke, Malcolm D. Mason, David P. Dearnaley, Alastair WS Ritchie et al. "Abiraterone for prostate cancer not previously treated with hormone therapy." New England Journal of Medicine 377, no. 4 (2017): 338-351.
  7. Davis, Ian D., Andrew J. Martin, Martin R. Stockler, Stephen Begbie, Kim N. Chi, Simon Chowdhury, Xanthi Coskinas et al. "Enzalutamide with standard first-line therapy in metastatic prostate cancer." New England Journal of Medicine 381, no. 2 (2019): 121-131.
  8. Armstrong, Andrew J., Russell Z. Szmulewitz, Daniel P. Petrylak, Jeffrey Holzbeierlein, Arnauld Villers, Arun Azad, Antonio Alcaraz et al. "ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer." Journal of Clinical Oncology 37, no. 32 (2019): 2974-2986.
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