Poor Efficacy of Immune Checkpoint Inhibitors Plus Chemotherapy in Lung Cancer Patients with EGFR/ERBB2 Exon 20 Insertion.

BACKGROUND

EGFR and ERBB2 exon 20 insertion (Ex20ins) account for a small fraction of patients with EGFR mutations. The efficacy of immune checkpoint inhibitors (ICIs) for these patients was still controversial.

METHODS

This retrospective study enrolled lung cancer patients harboring either EGFR or ERBB2 Ex20ins mutations. All the patients were treated with platinum-based chemotherapy plus ICIs, or platinum-based chemotherapy. The demographic features and clinical outcome of each patient were reviewed and analyzed.

RESULTS

When treated with immunochemotherapy, patients with EGFR/ERBB2 Ex20ins mutations ( = 31) had poor PFS compared with those without EGFR mutations ( = 141, 5.0 mon and 11.2 mon, < 0.001). When compared with those with EGFR classic mutations who received immunotherapy as the salvage therapy ( = 24), these patients with EGFR/ERBB2 Ex20ins mutations had similar PFS (5.0 mon and 4.1 mon, = 0.625), ORR (37.5% vs. 48.4%), and DCR (70.8% vs. 77.4%). In the patients with EGFR/ERBB2 Ex20ins mutations, the PFS of those treated with chemotherapy ( = 54) and those treated with immunochemotherapy ( = 31) was 6.5 mon vs. 5.0 mon ( = 0.066). In the EGFR Ex20ins subgroup, the PFS of addition of bevacizumab to chemotherapy ( = 20) and chemotherapy alone ( = 16) was 8.8 mon and 5.2 mon, respectively ( = 0.082) or immunochemotherapy ( = 15, 8.8 mon and 5.0 mon, = 0.097). Similarly, in the ERBB2 subgroup, the combination of bevacizumab and chemotherapy achieved a numerically longer PFS over chemotherapy alone (9.1 mon and 4.5 mon, = 0.253), but there was no statistical significance.

CONCLUSIONS

This study showed that platinum-based chemotherapy plus ICIs had limited efficiency compared to platinum-based chemotherapy for patients with EGFR/ERBB2 Ex20ins. Chemotherapy plus bevacizumab may be a potential scheme for these patients.