From the Journals

Specific prednisone regimen safer than others when used with abiraterone for mCR prostate cancer

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Glucocorticoid regimens: one size does not fit all

Data from this and similar trials of combination abiraterone and glucocorticoid therapy in prostate cancer should be incorporated into practice in a tailored manner, Umang Swami, MD, and coauthors maintain in an invited commentary (JAMA Oncol. Online June 27, 2019. doi:10.1001/jamaoncol.2019.1008).

“In our view, patients who are expected to be on long-term treatment with abiraterone acetate …. should receive prednisone, 5 mg, once daily to mitigate long-term metabolic toxic effects,” they recommend. However, when using this regimen in the population with metastases, oncologists will need to closely monitor serum potassium levels and blood pressure.

“In other circumstances, the corticosteroid dose will need to be individualized,” Dr. Swami and coauthors advise. “For example, a higher dose can be used for men who are nonadherent with close follow-up and when obtaining laboratory tests and close monitoring for mineralocorticoid excess may be difficult. On the other hand, a lower dose of prednisone is recommended for men who have considerable cardiovascular or metabolic comorbidities but who are otherwise compliant.”

Umang Swami, MD, University of Iowa Hospitals and Clinics, Iowa City,

Sumanta K. Pal, MD, City of Hope Comprehensive Cancer Center, Duarte, California, and Neeraj Agarwal, MD, University of Utah, Salt Lake City.


 

FROM JAMA ONCOLOGY

The safety profile of combination abiraterone acetate (Zytiga) and glucocorticoid therapy in men with metastatic castration-resistant prostate cancer (mCRPC) hinged on the specific steroid regimen, according to a phase 2 open-label randomized controlled trial.

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Glucocorticoids are added to abiraterone in part to prevent mineralocorticoid excess, but can also have adverse effects of their own, noted lead investigator Gerhardt Attard, MD, of the University College London Cancer Institute, London, and colleagues. Understanding of the comparative physiologic effects of various regimens is limited.

In the trial, the investigators randomized 164 men with mCRPC from 22 centers in 5 countries (median age 70 years) to 4 glucocorticoid regimens, each combined with abiraterone acetate, 1,000 mg, daily: prednisone, 5 mg, twice daily; prednisone, 5 mg, once daily; prednisone, 2.5 mg, twice daily; and dexamethasone, 0.5 mg, once daily.

Results reported in JAMA Oncology showed that the proportion of patients who had not developed toxicity (hypotension or hypokalemia) from mineralocorticoid excess during the first 24 weeks of treatment was highest, at about 70%, with prednisone, 5 mg, twice daily, and with dexamethasone, and only these regimens had confidence intervals excluding occurrence of this toxicity in at least half of patients. However, patients in the dexamethasone group had significantly heightened risks of insulin resistance and bone mineral density loss at the end of follow-up.

The median radiographic progression-free survival was 18.5 months in the group given prednisone, 5 mg, twice daily; 15.3 months in the group given prednisone, 5 mg, once daily; 12.8 months in the group given prednisone, 2.5 mg, twice daily; and 26.6 months in the group given dexamethasone, 0.5 mg, once daily.

“Different glucocorticoid regimens make distinct compromises on control of mineralocorticoid excess, changes in body composition, and development of insulin resistance,” Dr. Attard and coinvestigators summarized. “This trial provides results consistent with the approved use of abiraterone acetate with prednisone, 5 mg, twice daily for the treatment of mCRPC. Long-term adverse metabolic and musculoskeletal changes are small and do not appear to have a detrimental effect on patient-reported quality of life.”

At the same time, lower-dose prednisone regimens – with their more modest long-term risks of insulin resistance, increased body fat, and bone mineral density loss – can still be used, with caution. “With careful monitoring, the risk of hypokalemia with lower glucocorticoid doses can be mitigated, as demonstrated in the LATITUDE and STAMPEDE trials where no major safety concerns were raised,” they elaborated.

Dr. Attard disclosed personal fees, research support, and travel support from Janssen during the conduct of the study; as well as personal fees research, and/or travel support from numerous other pharmaceutical companies. The study was funded by Janssen EMEA.

SOURCE: Attard G et al. JAMA Oncol. Published online June 27, 2019. doi:10.1001/jamaoncol.2019.1011.

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