Real-World Experience in Toxicity with Bevacizumab in Indian Cancer Patients

Abstract

Background Bevacizumab, a humanized monoclonal antibody, known to block the binding of all known vascular endothelial growth factor-A isomers to their receptors, is used in solid cancers, especially in advanced settings where its role is proven to be stronger than localized stages. Furthermore, various studies have suggested that adding bevacizumab to first-line standard therapy in advanced solid cancers, such as colorectal cancer, lung cancer, ovarian cancer, renal cancer, and breast cancer, significantly prolongs progression-free survival, overall survival, and response rates. However, this ability is limited and variable in cancer subtype. The toxicity profile of bevacizumab is outspread, ranging from mild gastrointestinal side effects, proteinuria to life-threatening hemorrhagic tendency, ischemic thromboembolism, and intestinal perforation. However, it has never been studied in Indian subset of patients till date. Materials and Methods We performed an institutional retrospective study of 41 patients with a pathologically proven ovarian, colorectal, lung, mesothelioma, melanoma, round cell tumors, and GBMs who received bevacizumab (2.5 mg/kg/week [5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks]) with or without chemotherapy, between January 2016 and January 2019 at our center in North India. Results Forty-one patients, including 12 (29) advanced ovarian cancer, 12 (29) colon cancer, 10 (24) rectal cancer, 1 (2) appendicular cancer, 1 (2) mesothelioma, 1 (2) melanoma, 1 (2) desmoplastic round cell tumor, and 3 (7) GBM, were treated with bevacizumab. The incidence of arterial thrombus and hemorrhage was 2 and 10%, respectively, whereas venous thrombus and fistula were not seen and not related to age. No fatal adverse event was recorded. The global incidence of severe (grade 3/4) arterial hypertension (HTN) was 49%. It was safely managed in all cases, and no grade 4 (life-threatening complication) occurred. The incidence of severe HTN was significantly higher in elderly patients than in younger ones (72 vs. 40%), proteinuria was found to be more frequent in the younger age group as compared with older age group (7 vs. 3%). Also to note, the incidence of congestive heart failure and subacute intestinal obstruction was found in 5% of patients, wherein all four patients belonged to the older subgroup. Furthermore, Grade 3 hypersensitivity reaction was found in one patient in the younger subgroup which warranted immediate termination of bevacizumab.