Efficacy of camrelizumab (SHR-1210) plus apatinib with or without stereotactic body radiotherapy (SBRT) as higher-line therapy for advanced EGFR-mutant non-small cell lung cancer (NSCLC).

Abstract

e21128 Background: Despite the dramatic response of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) as first-line treatment for EGFR-mutant NSCLC, the development of resistance is inevitable. The application of third-generation EGFR TKIs is increasing, of which the resistance mechanism is unknow. To date, the optimal strategy has not been defined after failure of EGFR TKIs. Several studies reported the tumor immunogenicity is higher in patients with poor response to EGFR TKIs, suggesting that they may benefit from immunotherapy. Moreover, other studies showed that apatinib (a VEGFR2 TKI) and radiotherapy might augment anti-tumor activity of immunotherapy. In the present study, we reported the efficacy of camrelizumab (an anti-PD-1 antibody) plus apatinib with or without SBRT as higher-line therapy for EGFR-mutant NSCLC. Methods: In this single-arm trial, immunotherapy-naive, NSCLC patients aged 18-75 years, with EGFR-sensitizing mutations, and progression after at least one kind of EGFR TKI were enrolled. All patients received intravenous camrelizumab (200 mg, D1) plus oral apatinib (250mg daily, 5 days on, 2 days off) for a 21-day cycle until disease progression or intolerable toxicity. SBRT (24-30 Gy in three fractions) to at least one metastatic site was completed in some patients. SBRT was decided by the investigator, and patients should have at least one unirradiated lesion to monitor out-of-field response. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall response rate (ORR), and safety. Results: Up to Feb 1, 2021, 24 eligible patients were enrolled. Seven patients were excluded because of treatment discontinuation. Thirteen evaluable patients were included in the efficacy analysis. One had received osimertinib and three had received osimertinib after gefitinib resistance. All patients were previously treated with at least one lines of chemotherapy after EGFR TKI resistance. Eight patients received radiotherapy before enrollment. The median follow-up was 3.5 months (range: 0.7-7.8 months). The median number of cycles was 5 (3-11) PFS and OS data were immature. ORR and disease control rate was 15% (2/13) and 62% (8/13), respectively. Three received SBRT, with ORR of and no disease progression. Conclusions: Camrelizumab plus apatinib with or without SBRT as higher-line therapy showed benefit to patients with EGFR-mutant NSCLC. For patients treated with SBRT, the regimen may have better efficacy. Further investigation is warranted. Clinical trial information: ChiCTR1900028363.