Ramucirumab was associated with increased risks of serious or fatal adverse events, with only modest improvements in progression-free survival (PFS) or overall survival (OS) and no improvements in quality of life (QoL) among patients with advanced solid tumors, according to a meta-analysis published in EClinicalMedicine.

“Risk-benefit assessments are important for shared decision making regarding any cancer drug treatment,” the authors wrote. “The incidence and risks of serious and fatal adverse events, that have important consequences to the patients and family, are frequently overlooked during these discussions.”

Ramucirumab is an anti-VEGF2 receptor antibody that is approved by the US Food and Drug Administration for various solid tumors, including gastric cancer, non-small cell lung cancer, and colorectal cancer.

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The meta-analysis included 10 randomized controlled trials, including 6 that led to regulatory approvals of ramucirumab. The primary endpoint was to determine the risks and benefits of ramucirumab, with risks defined as serious or fatal adverse events and benefits defined as gains in QoL, PFS, or OS. The safety data were pooled across trials, but efficacy or benefit outcomes were not due to inherent differences between cancer types.

Among the 6905 patients included in the safety analysis, serious adverse events occurred more frequently in the ramucirumab arm across all trials at 37.5% compared with 33.5% in the control arm (relative risk [RR], 1.13; 95% CI, 1.05-1.21). Fatal adverse events also occurred more frequently with ramucirumab, with a cumulative incidence of 1.8% compared with 1.3% in the control arm (RR, 1.41; 95% CI, 0.96-2.07). There was no evidence of heterogeneity in either analyses.

Nine of the 10 trials demonstrated a significant improvement in PFS with ramucirumab compared with the control arm, with a median increase of 0.3 to 1.5 months, except an increase of 7 months in the RELAY trial.

OS was only improved in half of the trials, with a median gain in OS of 1.2 to 2.2 months.

QoL outcomes were measured in 7 of the trials; none showed an improvement in the ramucirumab arm compared with the control arm.

“We found that ramucirumab significantly increased the risks of serious adverse events while the treatment benefits were marginal to moderate at best,” the authors concluded. Therefore, “the risk-benefit balance of treatment with ramucirumab may be tilted more toward risks than benefits.”


Effing SMA, Gyawali B. Assessing the risk-benefit profile of ramucirumab in patients with advanced solid tumors: A meta-analysis of randomized controlled trials [published online July 15, 2020]. EClinicalMedicine. Doi: 10.1016/j.eclinm.2020.100458