Some VEGF Inhibitor Toxicities 'Inconsistently' Reported, Bristol-Meyers Squibb Researchers Note

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(ChemotherapyAdvisor)–Nausea, vomiting, hypertension and hemorrhage are the most common adverse events (AEs) seen among cancer patients administered vascular endothelial growth factor (VEGF) inhibitors; however there exist some inconsistencies in VEGF inhibitor drug label warnings, Bristol-Myers Squibb researchers report in the journal Cancer Epidemiology.

“The most common adverse event was nausea and vomiting (IR 651.7/1,000 person years; 95% CI 589.7-718.4),” reported lead author Brian Dreyfus, MPH, Department of Epidemiology, Bristol-Myers Squibb, Wallingford, CT, and coauthors. “Other common adverse events were hypertension (IR 452.9/1,000 person years; 95% CI 395.9-517.1) and hemorrhage (IR 375.2/1,000 person years; 95% CI 332.2-422.3).”

Bevacizumab, sunitinib, sorafenib, pazopanib, and vandetanib are examples of FDA-approved VEGF inhibitors, some of which are used to treat colorectal, nonsmall cell lung, breast, glioblastoma, renal cell carcinoma, hepatocellular carcinoma, gastrointestinal stromal tumor (GIST), pancreatic neuroendocrine and medullary thyroid cancers, Dr. Dreyfus's team noted.

“VEGF inhibitors were believed to result in less toxicity than standard chemotherapy by nature of being more selective in their targets; nonetheless, these compounds have unique safety profiles of their own,” the authors noted.

“While the safety profile of VEGF inhibitors has been studied extensively as part of clinical research there has been little to no research on the overall benefit risk profile of these medicines in population-based settings,” they wrote -- resulting in a “deep lack of knowledge” about adverse events (AEs) associated with these agents in clinical practice.

So the researchers conducted a retrospective cohort analysis of administrative claims database entries made during 2004-2010, extracting data for 2,326 patients with at least two malignant primary cancer diagnosis-related ICD-9-CM code entries for the same cancer site, and prescriptions for a VEGF inhibitor between January 2004-December 2010. The mean age of the cohort was 57.3 years (79% ≥ 50 years of age).

Similar to clinical studies, the analysis found hypertension, nausea and vomiting, and hemorrhage to be the most common VEGF inhibitor-associated adverse events. Formal statistical comparisons were not undertaken to compare AE rates associated with different VEGF inhibitors, but the agents “appeared to have overlapping toxicity profiles,” the authors reported.

However, the authors also noted inconsistencies on the reporting of some AEs on drug labels. For example, proteinuria is not listed on sorafenib's label, and bevacizumab's label does not mention dermatologic toxicity, the authors reported, although the new analysis indicates both occur at levels somewhat similar to other drugs, for which they are listed. Hypothyroidism rates were similar (but lower) among sorafenib treated patients compared to patients administered sunitinib, but hypothyroidism is listed as an “uncommon” AE for sorafenib, they noted. Cerebrovascular events have incidence rates of 120.4-127.7 per 1,000 person years for bevacizumab, sorafenib, and sunitinib, they noted, but are listed as “uncommon or observed in the post-marketing setting for sorafenib and sunitinib respectively.”

The authors emphasized that their database analysis lacked detailed clinical and laboratory findings, and relied on ICD-9-CM database code entries.

All authors of the analysis are employed by Bristol-Myers Squibb.

Abstract

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