Letrozole plus bevacizumab ‘feasible’ for metastatic breast cancer
MedWire News: Treatment with the aromatase inhibitior (AI) letrozole plus the anti-vascular endothelial growth factor (VEGF) antibody bevacizumab is feasible in postmenopausal patients with hormone receptor-positive metastatic breast cancer (MBC), US research shows.
“Preclinical models suggest that the use of anti-VEGF therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance,” say Maura Dickler (Memorial Sloan-Kettering Cancer Center, New York) and colleagues.
Dickler and team therefore performed a feasibility study to evaluate the safety, defined by grade 4 toxicity, of letrozole plus bevacizumab in patients with hormone receptor-positive MBC. A total of 43 patients were treated with letrozole (2.5 mg/day orally) and bevacizumab (15 mg/kg intravenously every 3 weeks).
After a median of 13 cycles, 58% of patients experienced hypertension (19% grade 2, 26% grade 3), 67% experienced proteinuria (14% grade 2, 19% grade 3), 51% experienced headache (16% grade 2, 7% grade 3), 74% experienced fatigue (19% grade 2, 2% grade 3), and 63% experienced joint pain (19% grade 2, no grade 3).
One patient experienced grade 4 hyponatremia and discontinued therapy. A further eight patients discontinued therapy because of drug-related toxicities: three due to grade 3 hypertension, three due to grade 3 proteinuria, one due to grade three headache and one due to grade 3 thrombocytopenia associated with portal hypertension.
Bevacizumab was added to ongoing non-steroidal AI therapy in 84% of patients, confounding efficacy results. Nevertheless, partial responses were seen in four (9%) patients and stable disease of 24 weeks or more was noted in 29 (67%) patients, giving a clinical benefit rate of 77%. The median progression-free survival was 17.1 months.
“The appropriate management of hypertension and proteinuria will be important for the feasibility of bevacizumab-containing treatment paradigms,” write Dickler and co-authors in the Journal of Clinical Oncology.
“Physicians should remain cautious about adverse events reported with combination anti-VEGF therapies, because some toxicity may be potentiated by anti-angiogenic effects,” they warn.
The researchers add: “Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).”
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By Laura Dean