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Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.
However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.
Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.
“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.
The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.
However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.
The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.
The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”
Caution needed when translating findings into clinical practice
The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.
“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”
The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.
Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.
“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.
She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”
The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.
However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”
There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.
Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.
“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
Study design and findings
From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.
Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.
The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).
The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).
The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.
After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.
About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.
In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).
In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.
The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.
The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).
The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.
The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.
A version of this article appeared on Medscape.com.
Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.
However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.
Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.
“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.
The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.
However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.
The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.
The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”
Caution needed when translating findings into clinical practice
The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.
“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”
The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.
Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.
“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.
She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”
The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.
However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”
There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.
Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.
“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
Study design and findings
From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.
Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.
The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).
The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).
The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.
After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.
About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.
In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).
In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.
The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.
The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).
The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.
The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.
A version of this article appeared on Medscape.com.
Patients with active cancer and newly diagnosed isolated distal deep vein thrombosis (DVT) who received 12 months of edoxaban (Savaysa) had fewer thrombotic events at 1 year than those who received 3 months of treatment, without significantly increased bleeding, in the ONCO-DVT trial.
However, lead author Yugo Yamashita, MD, of Kyoto University noted that caution is needed when determining anticoagulation strategies in individual patients with distal DVT, especially those with high risk for bleeding.
Dr. Yamashita presented the results at the annual congress of the European Society of Cardiology, and the trial was simultaneously published in the journal Circulation.
“This is the first and only randomized trial to show the superiority of longer duration over shorter duration of anticoagulation therapy for reducing thrombotic events in cancer patients with isolated distal DVT,” he said in a press briefing.
The results provide support for 12 months of edoxaban in patients with active cancer and isolated distal DVD, he said in an email.
However, “considering the risk of bleeding associated with anticoagulation therapy, physicians should make the decision of anticoagulation strategies for these patients based on risk-benefit balance of anticoagulation therapy in individual patients,” he stressed.
The take-home message for clinicians is that, “if you find minor DVT in cancer patients, please be careful, because their thrombotic risk was not low” in this trial, Dr. Yamashita said.
The study was conducted in Japan, so whether or not the results are generalizable to other populations is not clear. “Subgroup analysis based on body weight did not show any signal of different effect,” he noted, which suggests that the main results could be applied to other populations, including the U.S. population. However, “generalizability of the current results should be carried out carefully.”
Caution needed when translating findings into clinical practice
The assigned discussant, Teresa Lopez-Fernandez, MD, from La Paz University Hospital, Madrid, who was co-chairperson of 2022 ESC guidelines on cardio-oncology, noted that the optimal anticoagulation therapy strategy is unclear in patients with cancer and isolated distal DVT.
“2022 ESC guidelines on cardio-oncology and [European Society for Medical Oncology] guidelines from this year,” she said, “are both in agreement that we need to prolong anticoagulation [therapy to prevent venous thromboembolism (VTE)] when active cancer exists, and particularly in patients with metastatic cancer. The problem is that none of this text refers specifically to distal DVT.”
The ONCO-DVT trial sheds light on this, but there are a few points to consider when interpreting the findings.
Major bleeding was slightly increased in the 12-month vs 3-month edoxaban groups, although this was not statistically significant, she noted. Moreover, 75% of the patients were treated with low-dose edoxaban, mainly due to their low weight. Also, bleeding risk probably differs in different cancer types.
“These are important things that we need to keep in mind when we try to transfer this data to [inform] our clinical practice,” Dr. Lopez-Fernandez said.
She drew attention to a recent study based on RIETE registry data that suggests that “isolated distal DVT is a big problem for patients with cancer in comparison with noncancer patients, where it seems it’s a low-risk problem.”
The main takeaways from ONCO-DVT, Dr. Lopez-Fernandez said, are that it confirms that cancer-associated isolated distal DVT is a marker of poor prognosis, and it supports the need for extended anticoagulation in patients with active, ongoing cancer and isolated distal DVT.
However, “we need to be cautious to try to really understand what the bleeding risks of these patients are,” she said, “particularly because it is not always easy to transfer the results from an Asian population to other populations.”
There is also a need for further studies with other doses, with other novel oral anticoagulants, and in patients at high risk for bleeding, in clinical practice.
Dr. Yamashita said that the study suggests that there is a potential benefit of prolonged duration of anticoagulant therapy for some patients with isolated distal DVT, but not all patients should receive this dosing strategy, because some patients may be at high risk for bleeding or VTE recurrence. A subanalysis of data from ONCO-DVT study should shed further light on this.
“We need to individualize our risk stratification,” Dr. Lopez-Fernandez said, adding that notably, “a lot of patients in the 12-month group did not continue with the 12-month treatment,” which may have affected bleeding results. Dr. Yamashita agreed.
Study design and findings
From April 2019 to June 2022, the researchers enrolled and randomly assigned 604 patients with active cancer who had newly diagnosed isolated distal DVT, confirmed by ultrasonography, and were scheduled for DVT treatment with anticoagulation therapy, at 60 centers.
Active cancer was defined as a cancer diagnosis or cancer treatment (surgery, chemotherapy, radiotherapy, etc.) within 6 months of randomization, or current recurrence, local invasion, distant metastases, or hematopoietic malignancy without complete remission.
The most common reasons for ultrasonography were elevated D-dimer levels (62%) and suspected DVT because of symptoms (20%).
The patients had a mean age of 70.8 years and 28% were men. The most common cancer sites were ovaries (14%), uterus (13%), lung (11%), colon (9%), and pancreas (8%), followed by stomach, blood, and breast (each 5%).
The patients were randomly assigned 1:1 to receive 12 months or 3 months of oral edoxaban at a dose of 60 mg once daily or 30 mg once daily in patients with body weight of 60 kg or less, creatinine clearance of 30-50 mL/minute, or concomitant treatment with a potent P-glycoprotein inhibitor.
After excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group.
About 70% of patients had a body weight of 60 kg or less and about 22% had a creatinine clearance less than 50 mL/min. About three quarters received the lower dose of edoxaban.
In the 12-month edoxaban group, 223 patients completed the 1-year follow-up (66 patients had died and 7 were lost to follow-up). In the 3-month edoxaban group, 224 patients completed the 1-year follow-up (77 had died and 4 were lost to follow-up).
In the 12-month edoxaban group, 41% of the patients had discontinued treatment by 12 months. In the 3-month edoxaban group, 41% of patients had discontinued treatment by 3 months.
The primary endpoint – a symptomatic recurrent VTE event or VTE-related death – occurred in 3 of the 222 patients (1.2%) in the 12-month edoxaban group and in 22 of the 210 (8.5%) in the 3-month edoxaban group (odds ratio,0.13; 95% confidence interval, 0.03-0.44, P < .001). There were no VTE-related deaths.
The major secondary endpoint – major bleeding, according to International Society on Thrombosis and Hemostasis criteria – occurred in 28 of the 210 patients (10.2%) in the 12-month edoxaban group and in 22 of the 217 (7.6%) in the 3-month edoxaban group (OR, 1.34; 95% CI, 0.75-2.41, P = NS).
The researchers acknowledged that study limitations include an open-label design, a lower-than-expected primary endpoint rate, and less than high adherence to edoxaban, as well as the need for caution when generalizing the results to other populations.
The study was funded by Daiichi Sankyo. Dr. Yamashita disclosed receiving lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. Dr. Lopez-Fernandez disclosed receiving speaker fees from Phillips, Janssen, Daiichi Sankyo, Myocardial Solutions, AstraZeneca, Pfizer, Beigene, and Bayer not related to this study.
A version of this article appeared on Medscape.com.
FROM THE ESC CONGRESS 2023