Ramucirumab Safety in East Asian Patients: A Meta-Analysis of Six Global, Randomized, Double-Blind, Placebo-Controlled, Phase III Clinical Trials

Abstract

PurposeSeveral ramucirumab trials have reported a higher incidence of selected adverse events (AEs) in East Asian (EA) patients with cancer versus non-EA patients. A meta-analysis was conducted across six completed phase III trials to establish the safety parameters of ramucirumab in EA compared with non-EA patients.Materials and MethodsSix global, randomized, double-blind, placebo-controlled, phase III registration trials investigating ramucirumab were assessed. Relative risks (RRs) and 95% CIs were calculated for selected all-grade and grade ≥ 3 AEs using fixed-effects and mixed-effects models. Ratio of RR and number needed to harm were calculated for AEs (all grade and grade ≥ 3) between EA and non-EA patients.ResultsOf 4,996 randomly assigned patients receiving ramucirumab or placebo, 802 (16.1%) were EA (ramucirumab, n = 411; placebo, n = 391) and 4,194 were non-EA (ramucirumab, n = 2,337; placebo, n = 1,857). Patient baseline characteristics were generally balanced between treatment arms in EA and non-EA patients, excluding sex and body weight. Grade ≥ 3 AEs possibly associated with ramucirumab, which were increased in EA versus non-EA patients, included neutropenia (42.1% v 25.5%, respectively) and proteinuria (3.9% v 0.6%, respectively). There was an increase in the RR of several grade ≥ 3 AEs, including hypertension and proteinuria, in ramucirumab-treated EA and non-EA patients compared with placebo. The ratio of RR revealed no significant differences between EA and non-EA patients for all-grade and grade ≥ 3 AEs.ConclusionDespite the enhanced propensity of selected AEs in EA patients relative to non-EA patients, there were no substantial differences in the RR for AEs possibly associated with ramucirumab in these phase III trials.

Efficacy and Safety of Ramucirumab in Asian and Non-Asian Patients with Advanced Hepatocellular Carcinoma and Elevated Alpha-Fetoprotein: Pooled Individual Data Analysis of Two Randomized Studies

“…Importantly, there was no increase in high-grade AESI in Asian compared to non-Asian patients -this despite the prevalence of poor prognostic factors among Asian patients, potentially placing these patients at higher risk of developing adverse events following ramucirumab treatment, as well as the increased use of TACE in Asian patients, which may increase the risk of liver events. The overall observed safety profiles were consistent with those reported in other ramucirumab trials [16,17,[36][37][38][39]. Note that for the REACH-2 trial, patients with an intolerance to sorafenib were enrolled.…”

Efficacy and safety of targeted drugs in advanced or metastatic gastric and gastroesophageal junction cancer: A network meta‐analysis

“…However, our results showed that compared to other targeted drugs and placebos, ramucirumab did not significantly improve PFS and OS in GC and GEJC patients. A study based on six global phase III trials showed that the majority of AEs of using ramucirumab were manageable in east Asian patients and did not jeopardize their cancer therapy 56 . However, our study found that ramucirumab could cause severe AEs of all types, especially vomiting.…”

Aortic dissection after ramucirumab infusion

“…VEGF, in fact, plays a key role in the growth and functional maintenance of the vascular system, whose integrity is essential for cardiocirculatory function 16. Hypertension, sometimes severe, is the most common adverse event for this pharmacological class 8 17 18. For this reason, it is always advisable, and is routinely applied, to carry out a careful monitoring of blood pressure before the administration of ramucirumab, and during the treatment period, as well as for other anti-angiogenics.…”