The title of the talk by Celestia S. Higano, MD, New Developments in the Treatment of Hormone Refractory Prostate Cancer, was notable in the use of a term that has been replaced over the past decade with castration resistant. It was a change that Dr Higano, of the Fred Hutchison Cancer Research Center in Seattle, Washington, admits she did not support at the time.
The title of the talk by Celestia S. Higano, MD, “New Developments in the Treatment of Hormone Refractory Prostate Cancer,” was notable in the use of a term that has been replaced over the past decade with “castration resistant.” It was a change that Dr Higano, of the Fred Hutchison Cancer Research Center in Seattle, Washington, admits she did not support at the time.
But she acknowledged Saturday in presenting therapy options for these harder-to-treat patients that “refractory” really no longer applies, and that made for a challenging and interesting session at the National Comprehensive Cancer Network’s (NCCN) 19th Annual Conference: Advancing the Standard of Cancer Care, held in Hollywood, Florida.
Dr Higano presented a chart showing standard-of-care options for metastatic castration-resistant prostate cancer (mCRPC), which featured 9 different therapies across columns for patients at various points, from those with symptoms to those without, and for those who have already received docetaxel. Of the 6 therapies with level 1 evidence for survival benefits, only docetaxel itself had been approved “in the last 4 years,” she noted. (The others are sipuleucel-T, abiraterone, enzalutamide, radium 223, and cabazitaxel.)
With so many new therapies available, Dr Higano said the question becomes, “How do I decide what treatment is best in a given situation?” It comes down to what the patient presents: Are there
symptoms? If so, what are they? How fast is the disease progressing? Is there any presence of lung, liver, nodal, or soft tissue disease?
Dr Higano sought to break up the usual “pathway” chart oncologists often see and get down to basics: there are therapies for mCRPC patients without symptoms (immunotherapy and hormonal therapy, perhaps docetaxel), for those with symptoms (radium 223 is an option), and for those who have had docetaxel (cabazitaxel was listed as the first option).
More so than some of the NCCN presenters, she put forth highly challenging cases and treatment choices, and then reviewed the scattered responses with some strong feedback. A key moment came up regarding the immunotherapy sipuleucel-T, where Dr Higano sought to take on concerns about cost. “I would argue there are plenty of other therapies that are just as expensive,” she said.
Dr Higano suggested that immunotherapy involves a different process and thus requires a different way of thinking about costs and benefits, especially since the effects do not take hold immediately. To her, the evidence is clear: In the 2010 study published in the New England Journal of Medicine, at 3 years, the median survival benefit was 4.1 months and, more importantly, a 24.5% reduction on the risk of death.1 (Dr Higano was a coauthor on the study.) “Subsequent trials have confirmed the data, and with milder toxicities and a shorter period to the first use of pain medication, there are clear benefits,” she said.
When should immunotherapy be used? Dr Higano recommended early in course of mCRPC, before second-line hormonal treatments, corticosteroid use with chemotherapy and abiraterone. At this stage, patients are less likely to have symptoms or rapid progression or experience liver metastases.
If immunotherapy is used, Dr Higano recommends baseline imaging to assess pain and monthly follow-up to monitor the patient. Patient education about the differences in how the treatment works is important, she said.
Two hormonal therapies, abiraterone and enzalutamide, are also indicated for mCRPC in patients without symptoms. While abiraterone appears to show less time to chemotherapy than enzalutamide from the placebo arm of the phase 3 study, (8.4 vs 17 months), Dr Higano said it is very important to note that the abiraterone trial included prednisone in the placebo arm, while enzalutamide did not. “Prednisone, even by itself, is an active agent. That could have increase the difference between the two arms,” she said.
In discussing radium 223, Dr Higano emphasized it is indicated only when patients have shown symptoms. It is a calcium mimic and targets bone metastases; thus, she predicts that skeletal-related events will become an endpoint in upcoming studies. While it can only be handled and administered by a specialist in nuclear medicine, there are no restrictions on the patient coming into contact with others. It should not be combined with docetaxel. “That is too toxic,” she said.
In discussing cabazitaxel, Dr Higano offered what she labeled “practical” advice: reduce the initial dose to 20 mg/M2, use growth factor in all high-risk patients, and understand that a lack of pain progression does not mean a lack of clinical benefit.
The choices are challenging to be sure, but Dr Higano said that new sequencing and combination data will give oncologists better information to use when making decisions about treatment in the future.
Reference
1.Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;29363(5):411-422.
The Pivotal Role of Payers in Improving Health Equity, Maternal Health Care in the US
March 26th 2024A presentation at the Greater Philadelphia Business Coalition on Health's 2024 Women’s Health Summit discussed how payers, including employers and public entities, can strategically influence health care purchasing to prioritize maternal health and equity.
Read More
Oncology Onward: A Conversation With Penn Medicine's Dr Justin Bekelman
December 19th 2023Justin Bekelman, MD, director of the Penn Center for Cancer Care Innovation, sat with our hosts Emeline Aviki, MD, MBA, and Stephen Schleicher, MD, MBA, for our final episode of 2023 to discuss the importance of collaboration between academic medicine and community oncology and testing innovative cancer care delivery in these settings.
Listen
Dupilumab Considered Safe, Effective Treatment for Adolescent, Adult Patients With AD
March 20th 2024These posters both used the GLOBOSTAD study, which demonstrated through patient and physician assessments that dupilumab is a safe and effective treatment for adolescent and adult patients with atopic dermatitis (AD).
Read More
The Importance of Examining and Preventing Atrial Fibrillation
August 29th 2023At this year’s American Society for Preventive Cardiology Congress on CVD Prevention, Emelia J. Benjamin, MD, ScM, delivered the Honorary Fellow Award Lecture, “The Imperative to Focus on the Prevention of Atrial Fibrillation,” as the recipient of this year’s Honorary Fellow of the American Society for Preventive Cardiology award.
Listen
Racial Variations in Cardiovascular Outcomes Found in Hidradenitis Suppurativa Study
March 19th 2024Based on the findings, investigators acknowledged the critical need to consider racial differences when assessing patients with hidradenitis suppurativa. Health care providers should be vigilant in addressing cardiovascular risk factors in this population, recognizing and addressing racial disparities that may impact disease management.
Read More