Grace Lu-Yao, PhD, MPH
Pre-existing cardiovascular disease (CVD) was associated with an increased mortality risk during the first 6 months of abiraterone acetate (Zytiga) treatment in patients with advanced prostate cancer, according to a retrospective analysis presented during a media preview ahead of the 2019 AACR Annual Meeting.
The analysis found that the crude 6-month mortality risk ranged from 21.4% to 25.6% in patients with various types of CVD, as compared with 15.8% for those with no pre-existing CVD.
The researchers noted that clinical trials of abiraterone often exclude patients with CVD from enrolling, meaning clinical trial results may not be generalizable to these patients.
“Our data show that patients who have pre-existing cardiovascular disease experienced higher mortality after receiving abiraterone acetate compared with those who do not and the bulk of the survival differences occurred in the first 6 months,” lead study author Grace Lu-Yao, PhD, MPH, said in a press release. “These data also provide rationale for relaxing clinical trial exclusion criteria to ensure greater generalizability of trial results to the real world.
“It is very important that patients with advanced prostate cancer understand that the outcomes of abiraterone acetate treatment observed in clinical trials may not apply to patients in the real world, especially those not meeting the eligibility criteria of the clinical trials,” added Lu-Yao, who is associate director for Population Science at the Sidney Kimmel Cancer Center at Jefferson, and vice chair and professor in the Department of Medical Oncology at the Sidney Kimmel Medical College.
Lu-Yao et al identified 2845 patients in the SEER-Medicare database who were diagnosed with prostate cancer between January 1991 and December 2013, and treated with abiraterone between 2011 and 2014. The median patient age was 75 years. Of the overall population, 67.6% (n = 1924) had at least 1 pre-existing CVD.
Compared with the 15.8% crude 6-month post-abiraterone mortality rate for those with no CVD, the rate was higher for each of the pre-existing CVD categories the researchers assessed: ischemic heart disease (21.4%), stroke (22.1%), congestive heart failure (23.4%), atrial fibrillation (24.4%), and acute myocardial infarction (25.6%).
The researchers also examined hospitalization rates in the 6 months before and after initiation of abiraterone and found a significant increase in hospitalization, regardless of whether patients had CVD. The rate increased by 53% in patients without CVD, and by anywhere between 34% (atrial fibrillation group) to 55% (acute myocardial infarction group) in those with CVD.
Lu-Yao acknowledged the primary study limitation was that researchers could not assess the efficacy of abiraterone in the CVD population, “given the study’s retrospective nature, the presence of confounders such as variable disease states, and the inability to quantify expected survival without control groups.”
She also noted that the researchers “could not directly compare our study population against the inclusion/exclusion criteria of the pivotal abiraterone acetate trials due to insufficient clinical information from the SEER database.”
AACR President Elizabeth M. Jaffee, MD, deputy director, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, who moderated the media preview, commented on the significance of the study findings.
“This study highlights the importance of understanding pre-existing noncancer conditions and how patients will respond to cancer therapy…Clinical trials usually test new therapies in the healthiest patients—I think this has been rationalized as a safety measure by both investigators and sponsors in the past since we don’t know what these drugs will do to patients. However, this does not provide the real-world data we need once a drug is approved. [When] the drug is approved, all physicians can administer these drugs and we don’t really have a handle on who may have worse side effects from these [treatments].”
“Real-world data has become an important topic over the past couple years and we’ll be discussing this in many different forums at the annual AACR meeting. [There will be discussions] about real-world data and how do we incorporate it into our current approaches for testing new therapies, and in particular, how patients use their own real-world data to make decisions on new therapies,” added Jaffee.
She concluded that Luo et al’s study provided enough intriguing data to support a prospective collection of information in a phase IV post-approval analysis.
Grace Lu-Yao G, Keith SW, Gandhi K, et al. Clinical outcomes among patients treated with abiraterone acetate for advanced prostate cancer with pre-existing cardiovascular conditions. Presented ahead of the 2019 AACR Annual Meeting; March 29-April 3, 2019; Atlanta, GA.
<<< 2019 AACR Annual Meeting