In a not entirely surprising set of findings, data from a relatively large registry study — to be presented at an upcoming meeting of the American Association of Cancer Research (AACR) — suggest that treatment with abiraterone acetate raises risk for cardiovascular-related mortality among prostate cancer patients with known cardiovascular risk factors.
In assessing the data from this new report, it is important to understand that men with significant cardiovascular risk factors are commonly excluded from clinical trials of drugs like newer types of androgen suppressive therapies. For example, in the STAMPEDE trial, exclusion criteria included those with a history of severe angina or heart failure, and those with a recent myocardial infarct (a heart attack). However, the prescribing information for abirtareone acetate (Zytiga) does not include any specific warning about cardiovascular risk factors associated with use of this drug.
In the paper to be presented at the AACR meeting in Atlanta, GA, at the end of March, Lu-Yao and colleagues will report the following:
- 2,845 patients could be identified in a long-term registry database related to the treatment of advanced prostate cancer between 2011 and 2014.
- 1,924/2,845 patients (67.6 percent) had a pre-existing cardiovascular condition, and
- 40 percent of the patients had uncontrolled hypertension.
- Among patients treated with abiraterone acetate
- Patients with a pre-existing cardiovascular condition had higher 6-month mortality rates than those without a pre-existing heart problem.
- Within these first 6 months, the increased mortality risk levels were
- 25.6 percent for men with a history of acute myocardial infarction (AMI)
- 22.4 percent for men with atrial fibrillation (AF)
- 23.4 percent for men with congestive heart failure (CHF)
- 22.1 percent for men with a history of stroke
- 21.4 percent for men with ischemic heart disease
- 15.8 percent for men with no history of heart disease
Lu-Yao and her colleagues also showed that there was an increased risk for hospitalizations in the 6 months before and after starting abiraterone treatment.
Risk for hospitalization (the incidence rate ratio or IRR) was increased for
- Men with a prior history of cardiovascular disease, including
- Acute myocardial infarction (IRR = 1.44)
- Congestive heart failure (IRR = 1.35)
- Stroke (IRR = 1.30)
- Atrial fibrillation (IRR = 1.27)
- Ischemic heart disease (IRR = 1.22)
- Men with no prior history of cardiovacular disease (IRR = 1.43)
In this study, about 20 percent of the patients (n = 586) had had chemotherapy prior to any treatment with abiraterone acetate and the remaining 80 percent were chemotherapy-naive. However, the patterns for both early mortality and hospitalization are said to have been “quite similar.”
Now we should be clear that these data all come from a retrospective study, and the study’s limitations include things like the following:
- VariatIon in patients’ disease states
- Possible misclassification of patients’ cardiovascular disease
- No assessment of treatment efficacy
- No control group available to against which to assess expected survival for this patient population
- No clinical data to allow comparison of the study population to study populations in the pivotal trials of abiraterone acetate
However, for those patients with progressive prostate cancer and a prior history of cardiovascular disease, there now have to be some significant questions about the value of abiraterone acetate as a treatment for advanced prostate cancer. The critical point to be understood here is that there can be a big difference between the types of patients treated in pivotal clinical trials and the types of patients who get treated with a specific drug in the “real world” of clinical practice. This difference can have serious ramifications.
Source materials for this commentary include this media release issued by the AACR and this report on the MedPage Today web site (which also appears to be based on the AACR media release).
Filed under: Uncategorized | Tagged: abiraterone, cardiovascular, hospitalizaton, mortality, real world, risk, trials |
THE "NEW" PROSTATE CANCER INFOLINK 
In the foregoing is the remark: “However, the prescribing information for abirtareone (of course meaning abiraterone) acetate (Zytiga) does not include any specific warning about cardiovascular risk factors associated with use of this drug.” Say what?
FDA HIGHLIGHTS OF PRESCRIBING INFORMATION
————–WARNINGS AND PRECAUTIONS——————¬
• Mineralocorticoid excess: Use ZYTIGA with caution in patients with a history of cardiovascular disease. The safety of ZYTIGA in patients with LVEF < 50% or NYHA Class III or IV heart failure in Study 1 or LVEF < 50% or NYHA Class II to IV heart failure in Study 2 was not established. Control hypertension and correct hypokalemia before treatment. Monitor blood pressure, serum …
Dear Chuck:
With respect, this is a warning very specifically about mineralocorticoid deficiency, which is associated with cardiovascular co-morbidities. It is not a warding about risk for cardiovascular mortality.
Dear sitemaster:
I would prefer to take note of the specific sentence “Use ZYTIGA with caution in patients with a history of cardiovascular disease.” That statement is enough, within itself, to be concerned with the prescribing of abiraterone/Zytiga to any patient with “cardiovascular disease”! Mineralocorticoid deficiency is just one of many reasons why concern should be paid attention to anyone with known “cardiovascular disease!”
Dear Chuck:
You are of course fully entitled to your opinion, but what I am worried about is that physicians are not being given a clear warning that there appears to be a clinically significant (between 6% and 10%) absolute increase in risk for mortality associated with the use of abiraterone and a roughly 20% to 40% absolute increase in risk for hospitalization, when something like 65% of the patients being treated in the real world (as opposed to the world of clinical trials) have a prior cardiovascular co-morbidity. The current warning does not even suggest that level of risk, and the fact that clinicians don’t understand that level of risk is clear from the very high percentage of patients with cardiovascuklar disease who are being treated with this agent.