Safety Assessment on Serious Adverse Events of Targeted Therapeutic Agents Prescribed for RAS Wild-Type Metastatic Colorectal Cancer: Systematic Review and Network Meta-Analysis

Yeo Jin Choi, Chang-Young Choi, Sandy Jeong Rhie and Sooyoung Shin
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Yeo Jin Choi: Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea
Chang-Young Choi: Department of Internal Medicine, Ajou University Medical Center, Suwon 16499, Korea
Sandy Jeong Rhie: Graduate School of Converging Clinical & Public Health, Ewha Womans University, Seoul 03670, Korea
Sooyoung Shin: Department of Pharmacy, College of Pharmacy, Ajou University, Suwon 16499, Korea

IJERPH, 2022, vol. 19, issue 15, 1-18

Abstract: Despite substantially elevated risk of serious adverse events (SAEs) from targeted therapy in combination with chemotherapy, comprehensive pharmacovigilance research is limited. This study aims to systematically assess SAE risks of commonly prescribed targeted agents (bevacizumab, cetuximab, and panitumumab) in patients with rat sarcoma viral oncogene homolog (RAS) wild-type metastatic colon cancer. Keyword searches of Cochrane Library, Clinical Key and MEDLINE were conducted per PRISMA-NMA guidelines. Frequentist network meta-analysis was performed with eight randomized controlled trials to compare relative risk (RR) of 21 SAE profiles. The risks of hematological, gastrointestinal, neurological SAE were insignificant among targeted agents ( p > 0.05). The risk of serious hypertension was substantially elevated in bevacizumab-based chemotherapy ( p < 0.05), whereas panitumumab-based chemotherapy had markedly elevated risk of serious thromboembolism (RR 3.65; 95% CI 1.30–10.26). Although both cetuximab and panitumumab demonstrated increased risk of serious dermatological and renal toxicities, panitumumab-based chemotherapy has relatively higher risk of skin toxicity (RR 15.22; 95% CI 7.17–32.35), mucositis (RR 3.18; 95% CI 1.52–6.65), hypomagnesemia (RR 20.10; 95% CI 5.92–68.21), and dehydration (RR 2.81; 95% CI 1.03–7.67) than cetuximab-based chemotherapy. Thus, further studies on risk stratification and SAE management are warranted for safe administration of targeted agents.

Keywords: adverse events; bevacizumab; cetuximab; colorectal cancer; metastatic cancer; panitumumab; pharmacovigilance (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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