Incidence of venous thromboembolism (VTE) events in patients with EGFR-mutant non-small cell lung cancer (NSCLC) treated with amivantamab: A systematic review and combined meta-analysis of phase 3 randomized controlled trials.
Authors: Hazem Aboaid, Abbas Hussain, Riccesha Hattin, Savannah Schauer, Tel Schl, Rory Twells, Karl Aharonian, Ryan Parto, Rodd Rahmani, Chalette Lambert-Swainston, Daniel Thomas Jones, Ramaditya Srinivasmurthy, Kyaw Zin Thein
Journal: Journal of Clinical Oncology (2025)

12042 Background: Amivantamab is a bispecific antibody that was granted accelerated approval by the FDA in May 2021 for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. In addition, it also targets the mesenchymal-epithelial transition (MET) pathway which is involved in cancer cell proliferation. While amivantamab approval is considered a significant advancement in the EGFR-mutant lung cancer management, its introduction has raised concerns about potential new adverse events. This study aims to evaluate the incidence of venous thromboembolism (VTE) events in patients with EGFR-mutant NSCLC receiving amivantamab. Methods: We conducted a comprehensive literature search using MEDLINE and EMBASE databases from inception through December 31, 2024. Phase III randomized controlled trials (RCTs) utilizing amivantamab in EGFR-mutant NSCLC and reporting VTE adverse events were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was employed. Results: A total of 1,791 patients from three phase III RCTs (MARIPOSA n = 849, MARIPOSA-2 n = 636, PAPILLON n = 308) were included in the analysis. MARIPOSA tested amivantamab-lazertinib vs osimertinib vs lazertinib, while MARIPOSA-2 involved amivantamab-lazertinib-chemotherapy vs chemotherapy vs amivantamab-chemotherapy, and PAPILLON tested amivantamab-chemotherapy vs chemotherapy. Randomization ratios were 2:2:1, 2:2:1, and 1:1, respectively. The incidence of any-grade VTE was higher in the amivantamab group compared to the control group, with a rate of 25.90% vs 7.26% (RR, 3.69; 95% CI: 2.74-4.98; P &lt; 0.00001). VTE as a serious adverse event was reported higher in the amivantamab arm compared to the control arm, 5.69% vs 2.42% (RR, 2.36; 95% CI: 1.31-4.27; P = 0.004). There was no statistically significant difference between the two treatment groups in terms of incidence of high-grade VTE. A subgroup analysis based on the type of VTE was performed. Incidence of both pulmonary embolism (PE) and deep vein thrombosis (DVT) was higher in the amivantamab cohort compared to the control cohort, with a rate of 9.94% vs 3.75% (RR, 2.62; 95% CI: 1.50-4.58; P = 0.0007) and 7.97% vs 1.81% (RR, 5.0; 95% CI: 2.90-8.62; P &lt; 0.00001), respectively. Conclusions: This study showed increased risk of VTE events in patients with EGFR-mutant NSCLC treated with amivantamab-containing regimens compared to the standard arm. These findings highlight the importance of close monitoring for those events in order to early detect and provide the appropriate management. Further studies are needed to better understand this association between amivantamab and VTE.