Extended treatment with a lower dose of apixaban (Eliquis) is noninferior to the full dose at preventing recurrent venous thromboembolism (VTE) with less bleeding in patients with active cancer who have completed at least 6 months of anticoagulation therapy, results from the API-CAT trial show. Findings were presented at the American College of Cardiology Annual Scientific Session and simultaneously published in the New England Journal of Medicine.
“Our results indicate that these patients may be eligible to receive the reduced dose of apixaban for extended treatment,” said principal investigator Isabelle Mahé, MD, PhD, professor of internal medicine at Université Paris Cité in France and head of internal medicine at Assistance Publique Hôpitaux de Paris.
Discussant Bonnie Ky, MD, MSCE, director of the Thalheimer Center for Cardio-Oncology at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, congratulated Dr. Mahé and her team for “this truly seminal and, I believe, practice-changing study.”
Dr. Ky noted that although VTE rates have decreased in these patients during the past few decades, bleeding rates have increased. At the same time, substantial advances in cancer treatment have led to improved survival in patients with active metastatic cancer.
“This is increasingly becoming a chronic disease, and we need to mitigate these comorbid conditions that impact this growing population,” Dr. Ky said in the late-breaking trial session.
Addressing Key Gap in Care
International guidelines recommend anticoagulation, typically with a direct oral anticoagulant (DOAC), for 6 months in patients with cancer who develop a VTE, and to continue therapy for as long as the cancer remains active or is being treated, Dr. Mahé said. What happens after that initial 6 months is unclear. “The risk of VTE recurrence declines over time, especially beyond 6 months, whereas the risk of bleeding remains substantial,” she said.
To help address this gap, API-CAT enrolled 1,766 patients with active cancer and proximal deep vein thrombosis or pulmonary embolism who had received at least 6 months of anticoagulation. The patients were randomly assigned to receive either 2.5 mg or 5.0 mg apixaban twice daily for 12 months. The median age was 67.4 years, 56.6% were women, and the median time since the index VTE was 8.0 months.
After 12 months, recurrent VTE occurred in 18 patients (cumulative incidence, 2.1%) in the reduced-dose group and in 24 patients (cumulative incidence, 2.8%) in the full-dose group, which met the requirement for noninferiority (subhazard ratio, 0.76; 95% confidence interval [CI], 0.41–1.41; P=.001).
Clinically relevant bleeding, a composite of major bleeding or clinically relevant nonmajor bleeding, occurred in 102 patients (cumulative incidence, 12.1%) assigned reduced-dose apixaban and 136 patients (cumulative incidence, 15.6%) assigned full-dose apixaban (subhazard ratio, 0.75; 95% CI, 0.58–0.97; P=.03).
Major bleeding was observed in 2.9% vs 4.3% of patients, respectively. Mortality rates were similar in the reduced-dose and full-dose groups (17.7% vs 19.6%; P=.42).
Practice-Changing Results
Speaking with Oncology News Central (ONC), Dr. Mahé said that there is a great deal of variation and confusion in clinical practice because current guidelines recommend only extended anticoagulant therapy, not the optimal dose regimen.
“Some clinicians continue at the full dose and some others reduce the dose, depending on the profile of the patient,” she said. “If the patient is bleeding or at risk of bleeding, in practice, we lower the dose. If the patient has very active cancer with expanding tumoral disease, now we continue full dose because there is a relation between the activity of cancer and the risk of VTE recurrence.”
“This study demonstrated that we can lower the dose without exposing patients to an excess of VTE recurrence, and the lower dose results in lower bleeding complications,” Dr. Mahé said. “[The] API-CAT study will change practices, of course.”
“This is an important study because it does inform us how to take care of an important population of patients that unfortunately do have frequently high risk and frequently increased risk of thrombosis,” Manesh Raman Patel, MD, who was not involved in the study and is chief of cardiology and clinical pharmacology at Duke University School of Medicine in Durham, North Carolina, told ONC.
As to whether there is a drug class effect, he said, “what we know from DOAC studies, in general, and what we should know about antithrombotics studies is that you shouldn’t generalize an effect across multiple DOACs.”
“Excellent News”
During a press briefing, Diego Sadler, MD, section head of cardio oncology at Cleveland Clinic Florida in Weston, said that API-CAT is the first large trial to test a lower dose in this patient population. He agreed that the findings can change practice.
“This is excellent news for cardiologists and oncologists,” Dr, Salder said. “This impacts a large population: Just in the United States, there are 2 million active new cancers each year, and 20 million cancer survivors. A lot of these patients have a high incidence of embolic events, and they struggle with a high risk of bleeding.”
API-CAT “establishes apixaban, administered at a 2.5-mg twice-daily dose, as an appropriate regimen for anticoagulation beyond the first 6 months in patients with cancer,” Simon Noble, MD, codirector of the Marie Curie Palliative Care Research Group and director of population medicine at Cardiff University in the United Kingdom, writes in an accompanying editorial.
The trial set a very low bar for reporting clinically relevant nonmajor bleeding, Dr. Noble said, which is a strength because it recognizes that in this trial population, where more than 80% of patients had an incurable disease, the effect of bleeding on overall quality of life often takes primacy over whether the bleeding is classified as major or nonmajor.
API-CAT “provides clinicians with much-needed information for them to engage in meaningful dialogue with patients in order to make anticoagulation decision that are based on patients’ values and preferences,” Dr. Noble concluded.
API-CAT was funded by Bristol-Myers Squibb (BMS)-Pfizer Alliance.
Dr. Mahé reported consultancy fees from AstraZeneca and research grants and speaker fees from BMS-Pfizer and Leo Pharma.
Dr. Ky reported consultant fees/honoraria from AstraZeneca; other from Corvia, Impulse Dynamics, Medscape, and UpToDate; and research/research grants from Pfizer.
Dr. Patel reported no relevant conflicts of interest.
Dr. Sadler reported consultant fees/honoraria from Voronoi.
Dr. Noble reported no relevant conflicts of interest.
This article was originally published on April 4, 2025 on Oncology News Central, a HealthCentral Corporation site that digs deeper into the business of oncology and evolving cancer treatment.
