Bevacizumab versus Ramucirumab in EGFR-Mutated Metastatic Non-Small-Cell Lung Cancer Patients: A Real-World Observational Study

Abstract

The combination of bevacizumab or ramucirumab with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy, chemotherapy, or immunotherapy for non-small-cell lung cancer (NSCLC) patients with EGFR mutations could have survival benefits. However, no study, to date, has been conducted to compare the efficacy and safety of these two antiangiogenic therapies (AATs). Stage IIIB to IV EGFR-mutated NSCLC patients who received first-line EGFR-TKIs between January 2014 and May 2022 were enrolled. These patients were divided into two groups: those receiving bevacizumab and those receiving ramucirumab as a combination therapy in any line of treatment. Ninety-six patients were enrolled in this study’s final analysis. The progression-free survival (PFS) of patients who received front-line AATs combined with EGFR-TKI therapy was longer than that of patients receiving later-line AATs combined with other therapies (19.6 vs. 10.0 months, p < 0.001). No difference in overall survival (OS) was observed between front-line and later-line therapy (non-reach vs. 44.0 months, p = 0.261). Patients who received these two different AATs did not differ in PFS (24.1 vs. 15.7 months, p = 0.454) and OS (48.6 vs. 43.0 months, p = 0.924). In addition, these two AATs showed similar frequencies of the T790M mutation (43.6% vs. 38.2%; p = 0.645). Multivariate Cox regression analysis indicated several AAT cycles as an independent good prognostic factor in OS. The incidence of some adverse events such as bleeding and hepatitis was higher for bevacizumab than for ramucirumab but it was not significant. Front-line AAT and EGFR-TKI combination therapy improved the PFS of stage IV EGFR-mutated NSCLC patients. The effectiveness and safety of the two AATs were similar.

Clinical outcome of bevacizumab or ramucirumab combined with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as the first line therapy in susceptible EGFR‐mutated advanced non‐small‐cell lung

“…15 p = 0.014). 32 In line with their findings, our study of patients receiving an anti-VEGF agent as an add-on treatment to the first-line EGFR TKI also demonstrated similar PFS (median PFS: 24.2 vs. 21.9 months) and OS (median OS: 33.5 months vs. not reached) in bevacizumab and ramucirumab users. We also found that worse PS and multiple (≥3) metastatic sites were independent prognostic factors for poorer PFS, while the type of anti-VEGF agent was not.…”

“…The incidence of T790M mutation was not influenced by adding different anti‐VEGF agent. In a recent study evaluating the clinical outcomes of different anti‐VEGF agents as an add‐on therapy to an EGFR TKI, the rates of T790M detection were similar between patients using bevacizumab and ramucirumab (43.6% vs. 38.2%, p = 0.645) 32 . In line with the previous study, our study showed no significant difference in T790M detection rate between patients receiving add‐on bevacizumab and ramucirumab (32% vs. 63%) while only 64% of patients had T790M testing on disease progression.…”

“…Comparing the patients receiving add‐on bevacizumab and ramucirumab as the front‐line therapy, there was no significant difference in the PFS (median PFS: 24.1 vs. 15.7 months, p = 0.454) and OS (median OS: 48.6 vs. 43.0 months, p = 0.924). Multivariable analysis revealed that receiving eight or more cycles of the anti‐VEGF agent was an independent factor for better OS (HR [95% CI]: 0.45 [0.24–0.85]; p = 0.014) 32 . In line with their findings, our study of patients receiving an anti‐VEGF agent as an add‐on treatment to the first‐line EGFR TKI also demonstrated similar PFS (median PFS: 24.2 vs. 21.9 months) and OS (median OS: 33.5 months vs. not reached) in bevacizumab and ramucirumab users.…”

“…Till now, there was no prospective clinical study directly comparing the clinical outcomes between bevacizumab and ramucirumab as an addon treatment to an EGFR TKI for EGFR-mutated advanced NSCLC. In a recent retrospective real-world study enrolling 96 patients to compare the clinical outcomes between bevacizumab and ramucirumab as an add-on treatment to an EGFR TKI, erlotinib (44.8%) and afatinib (37.5%) were the most commonly used EGFR TKIs, while 42 patients received an anti-VEGF agent (23 and 19 patients used bevacizumab and ramucirumab, respectively) as the front-line therapy 32. Comparing the patients receiving add-on bevacizumab and ramucirumab as the front-line therapy, there was no significant difference in the PFS (median PFS: 24.1 vs. 15.7 months, p = 0.454) and OS (median OS: 48.6 vs. 43.0 months, p = 0.924).…”

Fármacos Anticorpos Monoclonais para o Tratamento do Câncer: uma Perspectiva Brasileira

“…Sete deles agem mantendo o processo de ação antitumoral das células T, no qual pembrolizumabe, nivolumabe, cemiplimabe, atezolizumabe e durvalumabe (Figura 2a) agem se ligando ao sistema PD-1/PD-L1 e ipilimumabe e tremelimumabe se ligam ao CTLA-4 (Figura 2a) 41 . Ainda há dois mAb que agem inibindo a angiogênese, ramucirumabe e bevacizumabe (Figura 2c) 42 . Além disso, há o anticorpo biespecífico amivantamabe (Figura 2c) que bloqueia o processo de sinalização de divisão celular 43 .…”