Akram Mesleh Shayeb, MD, University of California San Diego, Moores Cancer Center, La Jolla, CA, discusses results from a retrospective multicenter study evaluating cabozantinib in combination with direct anticoagulants or low dose molecular weight heparin in renal cell carcinoma (RCC).

These results were presented at the virtual 2021 ASCO Genitourinary Cancers Symposium.

Transcript

Hi, good afternoon. My name is Akram Mesleh Shayeb. I'm a hematology oncology fellow at the University of California San Diego, and it's my pleasure today to talk to you about our real-world data on cabozantinib and advanced renal cell carcinoma that was presented in the virtual 2021 ASCO genitourinary cancer symposium.

Venous thromboembolism is the second leading cause of death in patients with cancer. We know that cabozantinib is a tyrosine kinase inhibitor which targets vascular endothelial growth factor receptor, resulting in inhibition of angiogenesis, which is essential for tumor growth, progression, and survival.

It has been approved for multiple tumors, including the first- and second-line systemic therapy in patients with advanced or metastatic renal cell carcinoma. In patients with RCC, cabozantinib has demonstrated improved efficacy and improved survival based on results from METEOR Trial and the CABOSUN Trial as well.

In addition to angiogenesis, the VGFA pathway also plays a role in hemostasis. We know that there are several toxicities reported for cabozantinib, including 3% bleeding complications, 9% thromboembolism complication, and 1% gastrointestinal perforation.

Outside of clinical trials, the true thrombotic safety profile of cabozantinib is not well understood. Currently, a major obstacle in the field is that balancing concomitant use of cabozantinib with different anticoagulants, which are other drugs that affect hemostasis and could potentially lead to additive adverse effects.

Furthermore, the studies in the new era of direct oral anticoagulants have shown superiority to low-molecular-weight-heparin, and their use is more common nowadays. Meanwhile, the original trials of cabozantinib only allowed concurrent low-molecular-weight as an anticoagulant.

That was one of the reasons why we conducted this study, because there is limited safety data of cabozantinib with DOACs, and limited comparison between DOAC and low-molecular-weight-heparin when used concurrently with cabozantinib.

It's difficult to provide an accurate benefit-risk ratio on treatment and management of cancer-related thrombosis when using cabozantinib in patients with RCC. Our aim was to investigate the hemostasis safety profile of cabo with different anticoagulants in patients with advanced RCC.

We conducted a multicenter retrospective study across 7 sites. Basically, we included all adult patients with advanced RCC who are treated with cabozantinib, and we allocated into 3 different groups.

One group were patients with no anticoagulant. A second group was patients with DOACs, and a third group were patients with low-molecular-weight-heparin. We had a total of 180 patients that were reported in that ASCO GU symposium.

Then the anticoagulation could be for treatment of VTE, or it could also be for stroke prevention and AFib. Our primary end point was to evaluate the proportion of major bleeding events, incidents, as this is defined per the International Society of Hemostasis and Thrombosis Criteria, which are a standardized criteria for anticoagulant trials.

In addition, we wanted to look at the proportion of new or recurrent venous thromboembolism while on anticoagulants. The majority of our cohort were males with clear cell histology and who underwent nephrectomy and had intermediate or poor risk by risk stratification.

There was a wide variability in which line of therapy cabozantinib was provided with. About 20% of patients received it as first-line, 34% as second-line, and 45% as third-line.

When we looked at the major bleeding events, we found that zero patients with no anticoagulant had any major bleeding event, and there was 2 patients in the low-molecular-weight-heparin group, and 2 patients in the DOAC group who had major bleeding events.

Then we did an overall comparison of the major bleeding, and we found that there was a statistically significant difference between all three groups. After that, we looked at pairwise comparison, and we found that there was no difference between the patients who were on DOAC vs low-molecular-weight-heparin and in patients with DOAC vs no anticoagulant.

We did find, however, a difference between low-molecular-weight vs no anticoagulant, but the group with low-molecular-weight-heparin was small, so it's hard to provide definite conclusions about the significance of this number.

To summarize, we had 180 patients, and the patients who received a direct oral anticoagulant, the major bleeding events in that group was no different than the group with no anticoagulant. Based on this data, we can say that, in carefully selected patients, DOAC can be considered as concurrent medication in patients receiving cabozantinib.

We're currently still updating this cohort, and thus far, we have 260 patients. In this updated analysis, there's going to be more patients with low-molecular-weight-heparin. Hopefully, we will provide a little bit more insight into the differences in that particular group.   

Mesleh Shayeb A, Urman D, Dizman N, et al. Evaluation of cabozantinib (cabo) in combination with direct oral anticoagulants (DOAC) or low molecular weight heparin (LMWH) in renal cell carcinoma (RCC). Presented at: the virtual 2021 ASCO Genitourinary Cancers Symposium; February 11-13, 2021. Abstract 291.

Dr Mesleh Shayeb reports no relevant financial relationships.