PD-1 inhibitors plus chemotherapy in EGFR/ALK-positive NSCLC patients with brain metastases and disease progression after EGFR/ALK-TKIs therapy.

Abstract

Resistance to epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitors (TKIs) is a pervasive barrier in TKIs therapy for EGFR/ALK-positive non-small cell lung cancer (NSCLC) patients. Immune checkpoint inhibitor (ICI) monotherapy has exhibited an encouraging anti-tumor activity in high-selected EGFR/ALK-positive NSCLC patients with acquired resistance to TKI therapy. However, the effect of ICI plus chemotherapy therapy on those with brain metastases in this subset of patients is still unknown. From April 2019 to August 2021, EGFR-mutated or ALK-rearranged NSCLC patients who progressed after previous EGFR/ALK-TKIs with brain metastases and received ICI plus chemotherapy ± bevacizumab at Cancer Hospital of the Chinese Academy of Medical Sciences (CAMS) were included. We retrospectively analyzed the efficacy, toxicity and progression site after ICI treatment. A total of 19 patients were included in the study, including 16 (84.4%) patients with EGFR mutations, 2 (10.5%) with ALK translocations and 1 (5.3%) with RET rearrangement. All of the patients progressed after previous TKI therapy and had brain metastatic lesions when received ICI combination therapy. The overall response rate (ORR) and disease control rate (DCR) were 15.8 and 57.9%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 4.7months (95% confidence interval CI 0.43-8.96) and 19.2months (95% CI 15.08-23.29), respectively. The intracranial ORR was 10.5% and extracranial ORR was 15.8%, and the intracranial and extracranial DCR were 68.4 and 63.2%, respectively. The most common progression pattern was extracranial failure, and primary lesions enlargement rather than new sites metastases accounted for the vast majority of progressions. The most common grade 3-4 adverse event (AE) was leukopenia (31.6%), followed by neutropenia (26.3%), thrombocytopenia (10.5%) and rash (5.3%) successively. No grade 5 AE anddiscontinuation of ICI therapy for severe AEs were observed. ICI combined with chemotherapy ± bevacizumab might be effective and safe for EGFR/ALK-positive NSCLC patients who progressed after previous TKI therapy, and synergistic anti-tumor activity for brain metastases was also observed.