Safety Profile and Adverse Events Associated with Motesanib in Non-squamous Non-small-cell Lung Cancer

Background Non-small cell lung cancer (NSCLC) remains a major contributor to cancer-related deaths, with chemotherapy offering limited survival gains. Motesanib, a multi-targeted angiogenesis inhibitor, was studied in combination with carboplatin and paclitaxel (C/P) for NSCLC therapy. Nonetheless, inconsistent efficacy outcomes and notable side effects resulted in its withdrawal. This meta-analysis investigates the tolerability of motesanib + C/P versus placebo or bevacizumab in NSCLC patients. Objectives To determine the safety profile of motesanib + C/P in NSCLC, with a focus on adverse events (AEs) associated with treatment. Methods Relevant studies were sought by conducting searches in databases such as PubMed, Cochrane, Scopus, Google Scholar, and clinicaltrials.gov. Four randomized controlled trials (RCTs) were carried out with a total of 1,945 participants. Cochrane tools were used to assess bias, and statistical evaluation was conducted using RevMan 5.3. Results Motesanib did not significantly improve OS or PFS compared to placebo. However, it showed a higher likelihood of hypertension (RR = 3.41, 95% CI 2.74-4.24), gallbladder toxicity (RR = 14.04, 95% CI 3.80-51.93), diarrhea (RR = 2.33, 95% CI 1.95-2.78), vomiting (RR = 1.34, 95% CI 1.15-1.55), weight loss (RR = 2.22, 95% CI 1.73-2.85), dehydration (RR = 2.97, 95% CI 1.60-5.51), as well as proteinuria (RR = 3.10, 95% CI 1.56-6.14). Conclusions Motesanib does not provide a survival advantage over standard treatments and poses significant safety concerns, particularly regarding cardiovascular and gastrointestinal toxicity. These findings emphasize the need for cautious clinical use and further research into safer angiogenesis inhibitors for NSCLC. The findings are based on a limited number of RCTs (four studies), which should be considered when interpreting the results.