Risk of pulmonary toxicities in patients with EGFR-mutant non-small cell lung cancer (NSCLC) treated with amivantamab: A systematic review and meta-analysis of phase 3 randomized controlled trials.

Abstract

e24035 Background: Amivantamab is a novel bispecific antibody that inhibits tumor growth by targeting both the epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) receptors. Its accelerated approval by the FDA in mid 2021 for the treatment of EGFR-mutant non-small cell lung cancer (NSCLC), was considered an important advancement in the field of lung cancer management. However, as with any other new therapy, its introduction has also brought up concerns about possible new adverse events (AEs). This meta-analysis aims to explore the incidence of pulmonary toxicities in patients with EGFR-mutant NSCLC treated with amivantamab. Methods: A comprehensive literature search was conducted 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 pulmonary AEs were included. We used the Mantel-Haenszel method 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 applied. Results: The analysis included 1,791 patients from three phase III RCTs (MARIPOSA n = 849, MARIPOSA-2 n = 636, PAPILLON n = 306). 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 overall incidence of both interstitial lung disease (ILD) and pneumonitis was not statistically different between the amivantamab group and control group. However, when compared solely to chemotherapy by excluding MARIPOSA, the amivantamab cohort was noted to have a statistically significant higher incidence of both ILD and pneumonitis, with rates of 2.38% vs 0% (RR, 10.46; 95% CI: 1.37-79.89; P = 0.02) and 2.20% vs 0% (RR, 9.88; 95% CI: 1.29-75.68; P = 0.03), respectively. No statistically significant differences were noted between the two treatment arms in terms of incidence of pneumonia, any-grade or high-grade Covid-19 infections. Conclusions: This study revealed a higher risk of ILD and pneumonitis in patients with EGFR-mutant NSCLC treated with amivantamab combination regimens compared to chemotherapy alone. However, amivantamab has shown a similar safety profile to the standard treatment in terms of respiratory infections incidence. Prompt identification and providing the proper management and supportive care are crucial in managing those pulmonary toxicities, and ultimately, optimizing the patients’ quality of life.