The goal of this prospective study is to explore the safety and preliminary efficacy of stereotactic body radiotherapy (SBRT) combined with ORIENT-31 regimen (Sintilimab plus bevacizumab plus platinum-doublet chemotherapy) for advanced epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) patients who failed first-line third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. Participants will first receive the standard four-drug combination therapy: PD-1 antibody + vascular endothelial growth factor (VEGF) antibody + platinum + pemetrexed. The efficacy will be evaluated every two courses. According to the efficacy evaluation results, personalized SBRT was be administered.
ECOG performance status score of 0-1;
Histologically or cytologically confirmed stage IV primary non-small cell lung cancer;
EGFR-sensitive mutations (L858R, 19del);
Resistance to first-line treatment with third-generation EGFR-TKIs;
Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granulomatosis), etc.
Symptomatic interstitial lung disease or active infectious/non-infectious pneumonia.
Patients with risk factors for intestinal perforation: active diverticulitis, intra-abdominal abscess, gastrointestinal (GI) obstruction, abdominal cancer, or other known risk factors for intestinal perforation.
History of other malignant tumors.
Single group
ORIENT-31 regimen
DrugSintilimab plus bevacizumab plus platinum-doublet chemotherapy
SBRT
RadiationBased on the results of the response evaluation, personalized SBRT will be arranged after cycle 4: A. Complete response, CR: continue with maintenance therapy of PD-1 antibody + pemetrexed + VEGF antibody until disease progression, intolerable toxic side effects, or up to two years. B. Stable disease, SD/partial response, PR: if the residual lesions do not exceed three organs and five lesions, and if the investigator deems SBRT feasible, curative-dose stereotactic radiotherapy covering all residual lesions will be administered, with dosing based on the NRG-BR001 study. C. If the residual lesions exceed three organs or five lesions, SBRT (24 Gy/3 Fx) targeting 1-3 selected tumor lesions will be performed, and then continue with maintenance therapy of PD-1 antibody + pemetrexed + VEGF antibody until disease progression. D. Progressive disease, PD: subsequent treatment is conducted according to the standard guidelines.
Progression-Free Survival (PFS)
The time from the start of drug treatment until the documentation of disease progression or death from any cause, assessed according to the RECIST 1.1 criteria. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.
Overall Survival (OS)
The time from the start of drug treatment until death from any cause. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.
Objective Response Rate (ORR)
The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria.
Treatment-related adverse event (TRAE)
Investigator-assessed treatment-related adverse events were recorded and assessed according to CTCAE5.0.
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