Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis

Abstract

Immune checkpoint inhibitors (ICIs) combined with the anti‐angiogenesis drug bevacizumab is one of the future directions of immunotherapy. However, the potential adverse drug reactions (ADRs) caused by combination therapy remain unclear. Current research on ADRs of combination therapy in cancer patients is extremely limited. Our study aims to help determine the safety of combination therapy. We downloaded the ADR reports on combination therapy, from the first quarter of 2012 to the fourth quarter of 2021, from the FDA adverse event reporting system (FAERS) database and conducted a large‐scale retrospective study. The ADR signals were monitored by reporting odds ratio (ROR) and analyzing the risk of different ADRs in patients with Pan‐cancer. A total of 2094 cases were selected, after excluding duplicate data and the use of chemotherapy drugs. We evaluated the risk of ADR in Pan‐cancer patients. Combination therapy was an independent risk factor for adverse drug reactions associated with interstitial lung disease (OR: 8.62; 95% CI: 6.14‐12.10, P < .0001), hypertension (OR: 1.35; 95% CI: 1.11‐1.65, P < .01) and gastrointestinal bleeding (OR: 3.16; 95% CI: 2.21‐4.51, P < .0001). A subgroup analysis revealed that the risk of endocrine system‐related ADRs was elevated in patients receiving different combination therapies or with certain tumor types. We retrospectively studied the ADR of combination therapy in Pan‐cancer patients and analyzed the distribution characteristics of ADR from the perspectives of treatment strategy and cancer types to provide recommendations for the individualized management of patients receiving combination therapy.

Reply to: Comments on “Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis”

“…Thank you for the opportunity to respond to the comment by Dr Yoshiro Noguchi concerning our article entitled "Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis." 1 It is now widely accepted that there is no gold standard for monitoring adverse drug reaction (ADR) signals and that each monitoring method has strengths and weaknesses. 2 In his comment, Dr Noguchi pointed out the shortcomings of the reporting odds ratio (ROR) algorithm and recommended the use of the Ω shrinkage measure to verify ADR signals associated with the use of bevacizumab combined with immune checkpoint inhibitors (ICIs).…”

Sudden aortic dissection: A cautionary tale for the unexplained back pain during bevacizumab treatment

“…Presently, bevacizumab has been widely used in combination with chemotherapy for solid tumors on a global scale [1 , 2] , such as colorectal cancer and non–small-cell lung cancer. In clinicians, much attention is paid to avoid the perioperative use of bevacizumab and keep an eye on the risk of developing drug-related hemorrhage [3] . Although bevacizumab is considered to have relatively high safety advantages in clinical practice, the sudden and highly lethal acute type A aortic dissection (AAAD) events induced by it are not fully recognized in the use of bevacizumab, which can very easily lead to missed surgical opportunities for patients.…”

Comment on: “Adverse reactions associated with immune checkpoint inhibitors and bevacizumab: A pharmacovigilance analysis”

“…Gu et al used case data from the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to investigate the occurrence of adverse drug reactions (ADRs) associated with immune checkpoint inhibitors (ICIs) and bevacizumab. 1 To explore the drug-drug interaction signals (DDI signals) of ICIs and bevacizumab, The original article 1 calculated the reporting odds ratios (RORs) 2 and 95% confidence intervals of the concomitant use group. 1 A literature search was also conducted to discuss the signals obtained, and the article was carefully organized.…”

“…1 To explore the drug-drug interaction signals (DDI signals) of ICIs and bevacizumab, The original article 1 calculated the reporting odds ratios (RORs) 2 and 95% confidence intervals of the concomitant use group. 1 A literature search was also conducted to discuss the signals obtained, and the article was carefully organized. They state that current research on the ADRs of bevacizumab in combination therapy with ICIs is limited.…”

“…They state that current research on the ADRs of bevacizumab in combination therapy with ICIs is limited. 1 Therefore, the original article 1 may assist in appropriately implementing combination therapy with ICIs and bevacizumab.…”