Sumanta (“Monty”) Kumar Pal, MD, is a prostate and genitourinary cancers expert. He is an assistant clinical professor at the department of medical oncology & therapeutics research, and a co-director of the City of Hope’s Kidney Cancer Program in Duarte, California.
In this question-and-answer session, Cancer Therapy Advisor asked Dr Pal about the ongoing controversy, evidence base, and pivotal studies of intermittent versus continuous androgen deprivation therapy for prostate cancer, and the idea—a popular topic on online patient-support discussion groups—of drug “holidays.”
Cancer Therapy Advisor (CTA): Is there still a role for intermittent androgen deprivation therapy for prostate cancer? How has the discussion around intermittent androgen deprivation changed over the past decade?
Dr Pal: The discussion regarding intermittent androgen therapy reached its peak in 2013 with the discussion of results from a large Southwest Oncology Group study, SWOG-9346.1 In this study, patients with metastatic prostate cancer were randomized to receive intermittent or continuous androgen deprivation therapy. The goal of the study was to demonstrate non-inferiority, and continuous therapy was not found to be non-inferior to intermittent therapy. This study, among others, definitively supported the use of continuous therapy in patients with metastatic prostate cancer.
Dr Pal: Data pertaining to long-term side effects from SWOG 9346 were recently published in JAMA Oncology.2 In this study, Dawn Hershman, MD, and colleagues noted that there were no major differences in bone, endocrine or cognitive-related side effects, as one might anticipate. There was, curiously, an increase in the number of ischemic events and thrombotic events among patients receiving intermittent therapy.
CTA: What do the available clinical-trial data say about intermittent androgen deprivation’s effects on survival?
Dr Pal: Maha Hussain and colleagues recently summarized data from 7 phase 3 studies examining continuous versus intermittent androgen deprivation therapy.3 After a thorough analysis of these data, they concluded that no study to date demonstrates a superior survival with intermittent versus continuous therapy. As we pointed out earlier, SWOG 9346 suggests the opposite results: intermittent therapy is not non-inferior to continuous therapy.
CTA: Might any emerging or investigational prostate cancer biomarkers inform decision-making about intermittent androgen blockade?
Dr Pal: There are, unfortunately, no clinical or laboratory biomarkers that can inform the decision between intermittent and continuous therapy.
CTA: At online patient support and discussion groups, the idea of “drug holidays” is sometimes discussed as a way to reduce toxicities associated with cancer treatments in general. What do physicians and patients need to understand about the risks of “treatment holidays?”
Dr Pal: The risks and benefits of drug holidays differ in varying contexts. One can envision that in certain settings, brief drug holidays to alleviate toxicity could improve overall compliance and enhance therapeutic benefit. In the scenario of intermittent androgen deprivation therapy, however, one can experience a heightened risk of adverse events.
- Hussain M, Tangen CM, Berry DL, et al. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013;368(14):1314-25. doi: 10.1056/NEJMoa1212299
- Hershman DL, Unger JM, Wright JD, et al. Adverse health events following intermittent and continuous androgen deprivation in patients with metastatic prostate cancer. JAMA Oncol. 2016;2(4):453-461. doi: 10.1001/jamaoncol.2015.4655
- Hussain M, Tangen C, Higano C, Vogelzang N, Thompson I. Evaluating intermittent androgen-deprivation therapy phase III clinical trials: the devil is in the details. J Clin Oncol. 2016;34(3):280-285. doi: 10.1200/JCO.2015.62.8065