Immunotherapy for non-small cell lung cancer with EGFR or HER2 exon 20 insertion mutations: a real-world analysis

Due to less sensitivity to classic tyrosine kinase inhibitors, effective first-line treatment is limited in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) or human epidermal growth factor receptor 2 (HER2) exon 20 insertion (ex20ins) mutations. Meanwhile, the impact of driver genes on the efficacy of PD-1 inhibitors is discrepant. Our study aimed to assess the clinical response to immunotherapy in NSCLC patients with EGFR or HER2 ex20ins mutations. In parallel, patients treated with chemotherapy but without immunotherapy were included as controls.

We retrospectively reviewed patients harboring ex20ins mutations treated with immune checkpoint inhibitors (ICIs) and/or chemotherapy in the real world. The clinical response was assessed by progression-free survival (PFS) and the objective response rate (ORR). Propensity score matching (PSM) was performed to control for confounding factors between immunotherapy and chemotherapy.

Of 72 patients enrolled, 38 had been treated with one line of single-agent immunotherapy or combined therapy including immunotherapy, and 34 had received conventional chemotherapy without immunotherapy. Among patients treated with immunotherapy, the median PFS was 10.7 months [95% confidence interval (CI): 8.2-13.2 months] in the first-line setting, with an ORR of 50% (8/16). The median PFS was significantly longer in the first-line immunotherapy group than in the chemotherapy group (10.7 vs. 4.6 months, P<0.001). A trend of an increased ORR in patients who received ICIs was observed compared with chemotherapy, but there was no statistical difference (50% vs. 21.9%, P=0.096). After PSM, the median PFS with first-line immunotherapy was still longer than that with chemotherapy (10.7 vs. 4.6 months, P=0.028). Grade 3-4 adverse events (AEs) were observed in 13.2% (5/38) of patients, with the majority developing granulocytopenia (40%, 2/5). One patient discontinued treatment due to a grade 3 rash after three cycles of ICI plus anlotinib treatment.

The results showed that immunotherapy combined with chemotherapy may play a role in the first-line treatment of NSCLC patients with ex20ins mutations. This finding requires further investigation for application.