Targeted therapies for breast cancer increase thrombosis risk
Key takeaways:
- New findings show a significant increase in thrombosis incidence than previously reported trial data.
- Individualized risk assessments should guide use of anticoagulant prophylaxis.
SAN DIEGO — The true incidence of thrombosis among people who received targeted therapy for breast cancer is significantly higher than reported in prior clinical trials, according to study results.
The extent of the difference in thrombosis risk between real-world and trial setting surprised researchers, who presented their findings at ASH Annual Meeting and Exposition.
For example, the overall thrombosis rate among patients treated with cyclin-dependent kinase (CDK) 4/6 inhibitors was about 13%, according to investigator James Martin, MD, hematologist at Cleveland Clinic and assistant professor in hematology and oncology at Case Western Reserve University. However, the venous thromboembolism rate reported with abemaciclib (Verzenio, Eli Lilly & Co.) in prospective trials was about 5%, whereas rates with ribocliclib (Kisqali, Novartis) and palbociclib (Ibrance, Pfizer) were closer to 1%, Martin said.
“We expected the numbers to be a little bit higher than what was seen in the prospective data, just because often times these real-world patients are sicker or may have additional risk factors for the development of thrombosis,” Martin told Healio. “We were a little shocked at the degree of difference, though.”
Background and methods
Targeted molecular therapies — including CDK 4/6, PI3 kinase, poly(ADP)-ribose polymerase (PARP) and mammalian target of rapamycin (mTOR) inhibitors — have transformed the breast cancer treatment landscape.
However, these agents have been associated with elevated thrombosis risk, according to study background. The increased risk ranges from 0.6% to 6.1% for CDK 4/6 inhibitors, to 4.1% for PARP inhibitors. Prior trials showed no increased risk with everolimus or the PI3 kinase inhibitor alpelisib (Piqray, Novartis).
Martin and colleagues conducted a retrospective cohort study to assess thrombosis incidence among women with breast cancer who received targeted therapies in real-world settings. Researchers also analyzed risk factors for thrombosis.
Researchers used a de-identified national database with 85 contributing health care organizations to identify 13,717 adults diagnosed with breast cancer who received a CDK 4/6, PARP, mTOR or PI3 kinase inhibitor between March 2012 and April 2024. CDK 4/6 inhibitors analyzed in the analysis included ribociclib, palbociclib and abemaciclib.
Researchers excluded patients using anticoagulants.
They defined thrombotic events as arterial thrombosis (myocardial infarction or cerebral infarction) and venous thrombosis (venous thromboembolism or pulmonary embolism) that occurred at least 1 day after treatment initiation with agents of interest.
The analysis also included a comparison cohort of 776,940 patients with breast cancer who were not on treatment with the listed medications.
Results, next steps
Researchers reported overall thrombosis incidence of 13.96% among patients treated with CDK 4/6 inhibitors (ribociclib, 7.3%; palbociclib, 16.4%; abemaciclib, 12.3%).
In contrast, they reported thrombosis rates of 20.7% for those who received alpelisib, 19.5% for those who received everolimus and 7.5% among those who received the PARP inhibitor olaparib (Lynparza, AstraZeneca).
CDK 4/6 inhibitors of any kind (OR = 1.86; 95% CI, 1.34-2.6) and everolimus (OR = 1.68; 95% CI, 1.36-2.07) appeared associated with increased risk for arterial clots.
Results showed elevated risk for VTE among patients treated with CDK 4/6 inhibitors (OR = 1.88; 95% CI, 1.51-2.34), everolimus (OR = 2.28; 95% CI, 1.97-2.63) or alpelisib (OR = 1.84; 95% CI, 1.47-2.28), but not those treated with olaparib.
Risk factors associated with thrombosis development included nicotine dependence (OR = 1.51; 95% CI, 1.29-1.76), prior venous thrombosis (OR = 6.21; 95% CI, 4.91-7.84), prior arterial thrombosis (OR = 4.41; 95% CI, 3.45-5.61) and brain metastases (OR = 1.41; 95% CI, 1.13-1.74).
“You have to take [these data] with a grain of salt because [they’re] retrospective data in a big cohort, and you don’t always have the granularity that you want in a perfect world,” Martin told Healio. “However, let’s say you have a patient with advanced breast cancer and you calculate their clinical risk for VTE using something like a Khorana score, and they’re high risk, so you’re debating whether to put them on an anticoagulant for VTE prophylaxis. I would say maybe look at the medication that you're going to start with them and, if it's one of these higher-risk medications, it may prompt you to consider putting them on anticoagulant prophylaxis because their risk is probably a little bit higher than one would think.”
For more information:
James Martin, MD, can be reached at martinj90@ccf.org.
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Guzick GL, et al. Abstract 1263. Presented at: ASH Annual Meeting and Exhibition; Dec. 7-10, 2024; San Diego.