Exploration of efficacy of the first-line treatment for advanced non-small cell lung cancer with primary MET-amplification: Retrospective evaluation of 36 cases.

BACKGROUND

There are few clinical data on targeted therapy for primary mesenchymal-epidermal transforming factor amplification (METamp), unlike METamp secondary to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). First-line treatment options for patients with primary METamp NSCLC remain unclear, and in particular, the efficacy of immune checkpoint inhibitors (ICIs) in these patients is controversial.

METHODS

We retrospectively included primary METamp patients who had received at least one line of systemic anticancer therapy, diagnosed at Zhejiang Cancer Hospital from June 2018 to June 2023, and analyzed the efficacies of different treatment patterns for these patients. We also evaluated the potential relationship between the tumor immune microenvironment (TIME) and the programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) axis in primary METamp NSCLC patients. High-level METamp was defined as gene copy number (GCN) ≥ 10 [1]. The clinical outcomes included objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS).

RESULTS

We screened 2016 NSCLC patients and detected 36 primary METamp, resulting in a prevalence of 1.79 %. Among the patients, the average MET GCN was 4.6, the overall ORR was 50.0 %, DCR was 77.8 %, mPFS was 5.8 months and mOS was 11.7 months. We categorized the first-line treatments that patients received as: immuno-chemotherapy (CI-group), antiangio-chemotherapy (CA-group), chemotherapy (C-group) and MET-TKIs therapy (TKI-group). The ORR of CI-group, CA-group, C-group and TKI-group was 64.3 %, 16.7 %, 33.4 % and 71.4 %, respectively. And the DCR of this four groups was 100 %, 50 %, 66.7 % and 71.4 %, respectively. CI-group achieved longer mPFS and mOS than other groups, respectively (mPFS: 8.63 vs 3.73 vs 3.53 vs 5.50 months, P = 0.021; mOS: 15.10 vs 11.73 vs 9.93 vs 13.93 months, P = 0.023). The mPFS was longer in the PD-L1-positive group than in the PD-L1 negative group (P = 0.046) and PD-L1 positivity was an independent prognostic indicator for PFS (P = 0.005). In addition, the disease remission effect was significantly lower in Foxp3-positive expressors than in negative expressors (ORR: 33.3 % vs 75.0 %, P = 0.024).

CONCLUSIONS

Immuno-chemotherapy is a first-line optional treatment strategy in addition to targeted therapy for NSCLC patients with primary METamp. Foxp3-negative expression better predicts the near-term efficacy of immunotherapy.