Cabozantinib as a single-agent does not have significant activity in patients with relapsed and/or refractory multiple myeloma, according to a research letter published in the journal Blood.1
Although newer agents have improved outcomes of patients with multiple myeloma, most patients will still develop disease recurrence following primary therapy. Therefore, researchers sought to evaluate cabozantinib, a small molecule inhibitor of hepatocyte growth factor receptor protein, vascular endothelial growth factor receptor 2 (VEGFR2), and RET, in patients with relapsed/refractory myeloma.
For the phase 1b study, researchers enrolled 12 patients at Memorial Sloan Kettering Cancer Center in New York, NY, and Massachusetts General Hospital Cancer Center in Boston, MA.
Of those, 100% had received a prior proteasome inhibitor and an immunomodulatory agent. Half had received prior carfilzomib and 17% had received prior pomalidomide. All participants received cabozantinib at a dose of 20 mg, 40 mg, or 60 mg orally once daily during each 28-day cycle.
Results showed that 1 patient achieved a minimal response, 8 had stable disease, and 2 had progressive disease. One patient was not evaluable for response.
In terms of safety, 2 patients experienced serious adverse events that were potentially related to cabozantinib therapy. The most common non-hematologic adverse events were diarrhea, abdominal pain/bloating, nausea/anorexia, dysgeusia, ALT/AST elevation, lipase/amylase elevation, hyperglycemia, hypocalcemia, hypomagnesemia, and hypophosphatemia.
Of note, 1 patient experienced a dose-limiting toxicity and 4 withdrew consent due to toxicities.
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Although this study did not demonstrate significantly activity with single-agent cabozantinib, there is a possibility that cabozantinib may have activity in patients with higher levels of hepatocyte growth factor or where disease is driven by hepatocyte growth factor.
- Lendvai N, Yee AJ, Tsakos I, et al. Phase IB study of cabozantinib in patients with relapsed and/or refractory multiple myeloma [published online ahead of print March 28, 2016]. Blood. doi: 10.1182/blood-2016-01-694786.