VTE Risk in Recurrent Ovarian Cancer Increases With More Lines of Chemotherapy

TAMPA, Fla. -- As lines of therapy increased for recurrent ovarian cancer, so did the risk of venous thromboembolism (VTE), a retrospective study showed.

Almost 80% of VTEs occurred in patients who had received three or more chemotherapy regimens. Almost three-fourths of the events occurred while patients were on chemotherapy.

Although VTE did not adversely affect overall survival (OS), the events were associated with significant morbidity, including hospital admission and bleeding complications related to anticoagulation, reported Erika J. Lampert, MD, of the Cleveland Clinic, at the Society of Gynecologic Oncology (SGO) annual meeting.

"We found among our patients with VTE that two-thirds had an intermediate- or high-risk Khorana score of 2 or greater," said Lampert. "However, a Khorana score of 2 or higher was not predictive of a VTE during third-line treatment. We calculated a Khorana score for all patients at the start of their third line of chemotherapy. There was no significant difference between the patients who did not develop a VTE and those who did."

"One in five patients with recurrent ovarian cancer developed a VTE," she added. "This is higher than previous estimates in the literature and likely reflects the heavily treated nature of our cohort. ... The risk of VTE was higher while receiving chemotherapy and with increasing lines of chemotherapy. This suggests that a prospective study of VTE risk in a heavily treated recurrent ovarian cancer population is certainly warranted."

Malignancy creates a hypercoagulable state that confers an increased risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE). In patients with primary ovarian cancer, VTE is associated with a 2.5 to 4.7 times greater risk of death, as well as lower quality of life. Previous studies estimated the incidence of VTE at 5.2% in primary ovarian cancer and 7% in second-line recurrent ovarian cancer.

Limited data have accumulated regarding the incidence and predisposing factors for VTE in a heavily treated recurrent ovarian cancer population, said Lampert. Given the substantial morbidity and mortality risk associated with VTE, multiple studies have examined thromboprophylaxis for patients with cancer.

The Khorana score is used to predict the risk of VTE in patients with solid tumors initiating chemotherapy, Lampert noted. The score incorporates information such as a patient's prechemotherapy platelet and white blood cell count, as well as hemoglobin and body mass index. A score ≥2 represents high risk for VTE. The randomized AVERT trial showed that thromboprophylaxis with apixaban significantly reduced the risk of VTE in patients initiating chemotherapy for cancer with a Khorana score ≥2.

According to an SGO clinical practice statement, "High-risk outpatients with gynecologic cancer initiating chemotherapy may be offered thromboprophylaxis."

Lampert and colleagues performed a retrospective analysis to report VTE incidence in patients with heavily treated recurrent ovarian cancer, assess the impact of VTE on survival and surrogates for quality of life, and evaluate predictors of VTE to identify patients who might benefit from thromboprophylaxis. Data for the analysis came from records of patients treated for epithelial ovarian cancer at the Cleveland Clinic from 2007 to 2020. The analysis was limited to patients who received at least second-line therapy.

The analysis included 345 patients, 22% of whom developed a VTE. A review of baseline characteristics showed no significant differences between patients who had VTEs and those who did not. The VTE group had received five lines of chemotherapy versus four for the patients who did not develop a VTE (P=0.012). The total VTE count consisted of DVT in 40 patients, PE in 30, and both in five.

Of the 56 patients who had a VTE during chemotherapy, 44 had received three to more than eight lines of chemotherapy, while 12 had received two lines.

Patients with and without VTE had similar survival. However, 54.5% with VTE required hospital admission, and 11.7% had bleeding complications related to anticoagulation.

Lampert and colleagues compared Khorana risk scores in patients with and without VTE during the third line of chemotherapy. Among 15 evaluable patients who had VTE, seven had a Khorana score of 1 (low risk) and eight had an intermediate-/high-risk score (P=0.24).

In a multivariate analysis, the number of lines of chemotherapy emerged as an independent predictor of VTE risk (OR 1.14, 95% CI 1.02-1.28, P=0.026). Age, body mass index, and American Society of Anesthesiology risk score were not predictive.

The study is "clinically interesting and very relevant" to clinical practice, said Alex Melamed, MD, of the Mass General Cancer Center in Boston, during a discussion that followed the presentation. Noting that "people have to remain alive long enough to get a DVT for you to measure them and categorize them as having a DVT," he asked Lampert whether the investigators accounted for immortal time bias in calculating survival.

"That's an excellent point, and we did not incorporate that into the survival analysis," she responded. "Certainly, when we look to publish this work, we will look into that."

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