Evaluating the Efficacy and Safety of Amivantamab and Lazertinib in Treating EGFR-Mutated NSCLC
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on December 2nd, 2024
|
Mutations in the epidermal growth factor receptor (EGFR) are common in patients with non-small-cell lung cancer, leading to a reduced 5-year survival rate of just 19%. Osimertinib is the current first-line therapy for these patients, working by inhibiting the kinase activity of EGFR (EGFR-TKI). However, nearly all patients eventually develop resistance to osimertinib and other third-generation EGFR-TKIs. To address this issue, Janssen sponsored a study to evaluate the efficacy of amivantamab and lazertinib in treating non-small-cell lung cancer with EGFR mutations.
The phase 3 clinical trial involved 1,074 patients diagnosed with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR mutation. Of these, 60% had an exon 19 deletion, while the remaining patients had a leucine-to-arginine mutation at the 858th residue. Participants were randomly assigned to receive either osimertinib, lazertinib, or a combination of amivantamab and lazertinib. Amivantamab is a bispecific antibody that binds to EGFR on the surface of tumor cells and recruits immune cells to initiate a cytotoxic response. Lazertinib, a third-generation EGFR-TKI, is effective against certain mutated versions of the EGFR receptor. Amivantamab was administered intravenously at a dose of 1,050 mg weekly for the first four weeks, followed by a change to every 2 weeks. Osimertinib and lazertinib were given orally at daily doses of 80 mg and 240 mg, respectively. After a median follow-up of 22 months, the researchers found that the combination of amivantamab and lazertinib reduced the risk of disease progression by 30% compared to those treated with the standard regimen of osimertinib. However, the use of the amivantamab-lazertinib combination significantly increased the risk of adverse events such as venous thromboembolism and hypoalbuminemia, leading to a higher rate of treatment discontinuation. The authors noted that future studies should have a longer follow-up period, as the current study’s duration was insufficient to assess mortality risk between treatments. Additionally, due to the intravenous administration of amivantamab, the study did not include a placebo-matched group for the non-amivantamab cohort, introducing a potential placebo effect.
The phase 3 clinical trial involved 1,074 patients diagnosed with locally advanced or metastatic non-small-cell lung cancer (NSCLC) with an EGFR mutation. Of these, 60% had an exon 19 deletion, while the remaining patients had a leucine-to-arginine mutation at the 858th residue. Participants were randomly assigned to receive either osimertinib, lazertinib, or a combination of amivantamab and lazertinib. Amivantamab is a bispecific antibody that binds to EGFR on the surface of tumor cells and recruits immune cells to initiate a cytotoxic response. Lazertinib, a third-generation EGFR-TKI, is effective against certain mutated versions of the EGFR receptor. Amivantamab was administered intravenously at a dose of 1,050 mg weekly for the first four weeks, followed by a change to every 2 weeks. Osimertinib and lazertinib were given orally at daily doses of 80 mg and 240 mg, respectively. After a median follow-up of 22 months, the researchers found that the combination of amivantamab and lazertinib reduced the risk of disease progression by 30% compared to those treated with the standard regimen of osimertinib. However, the use of the amivantamab-lazertinib combination significantly increased the risk of adverse events such as venous thromboembolism and hypoalbuminemia, leading to a higher rate of treatment discontinuation. The authors noted that future studies should have a longer follow-up period, as the current study’s duration was insufficient to assess mortality risk between treatments. Additionally, due to the intravenous administration of amivantamab, the study did not include a placebo-matched group for the non-amivantamab cohort, introducing a potential placebo effect.