Evantumumab first-line treatment of advanced non-small cell lung cancer with EGFR gene exon 20 insertion mutation

Introduction: In the NCCN Non-Small Cell Lung Cancer Clinical Practice Guidelines 2024 v2, for patients with non-small cell lung cancer (non-squamous cell carcinoma) carrying EGFR ex20ins, first-line treatment is strongly recommended combined with carboplatin and pemetrexed. This program has been verified by clinical trials and has demonstrated significant therapeutic effects, providing patients with a new treatment option. The introduction of evantumumab brings hope to this special group of patients, and is expected to improve their quality of life and prolong survival.

Pharmacological effects

Evantumumab, with its unique bispecific design, acts on two key targets, EGFR and MET, at the same time. It can precisely block the activation process of receptor-antibody complexes, thereby promoting the degradation of these complexes, thereby effectively inhibiting the conduction of downstream signaling pathways. This mechanism of action allows evantumumab to exhibit unique efficacy in the treatment of related diseases, providing the medical community with new treatment strategies.

Therapeutic effect

In a dose expansion study, 81 NSCLC patients carrying EGFR ex20ins who progressed on platinum-based chemotherapy received 1 050 mg of evantumumab, and the patients had ORR was 40%, including 3 cases of complete remission (CR) and 29 cases of PR. The median duration of response (DOR) was 11.1 months, and there was no significant difference between ex20ins mutation subtypes. PFS reached 8.3 months, and OS reached 22.8 months. Compared with global data, the Asian population subgroup is also highly consistent with global study results, indicating that there is no racial difference in the treatment of EGFR ex20ins mutation NSCLC with evantumumab.

Safety

The side effects of patients receiving evantumumab combination therapy mainly focus on reversible hematological effects and EGFR-related reactions. Although most patients tolerated treatment, 7% discontinued treatment due to adverse effects. Common side effects include neutropenia, periungual inflammation, rash, and anemia. Patients should be closely monitored during treatment, and treatment plans should be adjusted promptly if serious side effects occur.