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SummaryBackground To evaluate the efficacy and safety of neoadjuvant sintilimab, a programmed cell death 1 protein (PD-1) blockade combined with chemotherapy in patients with resectable stage II-IIIB epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Methods This was a single-arm, open-label, phase II trial (CTONG2104) conducted in China. Patients with resectable stage II-IIIB EGFR (AJCC 8th edition) mutant NSCLC were enroled and received neoadjuvant sintilimab (200 mg) plus carboplatin (area under the curve 5) and nab-paclitaxel (260 mg/m2) for 3 cycles. Patients in stage II cohort received adjuvant osimertinib for up to 2 years while observation for stage I cohort. The primary endpoint was major pathological response (MPR) rate (per IASLC criteria) in patients who received at least one dose neoadjuvant sintilimab plus chemotherapy. Secondary endpoints included pathological complete response (pCR) rate (per IASLC criteria), objective response (ORR) rate (per RECIST), event-free survival (EFS), overall survival (OS) and safety profile in all enroled patients. This study is registered with ClinicalTrials.gov, NCT05244213. Findings Between May 10, 2022, and March 20, 2024, 35 eligible patients (median range age, 60 48–73 years; 18 51.4% female) were enroled and received neoadjuvant treatment and 33 (94.3%) completed surgical resection. The median follow-up was 33.7 months. The primary endpoint was met, with a MPR following neoadjuvant immunochemotherapy of 34.3% (95% CI 19.1–52.2). The ORR and pCR was 60.0% and 11.4%, respectively. Patients with RB1 or RBM10 co-mutations respond well to neoadjuvant immunochemotherapy while opposite for EGFR tyrosine kinase inhibitors (TKIs). The median EFS was not reached with 2-year EFS rate of 71.4% (95% CI 57.9–88.1%). The safety profile during neoadjuvant treatment was tolerable, with 29% of patients experiencing grade 3-4 adverse events. All patients underwent minimally-invasive surgery with 87.9% achieved R0 resection. 42.9% patients experienced local relapse and oligo-metastasis, respectively and 81.8% achieved objective response after receiving EGFR-TKIs. Interpretation Neoadjuvant sintilimab plus chemotherapy revealed encouraging clinical and pathological response with well tolerability in EGFR-mutant NSCLC. Upfront immunochemotherapy did not add sever immune toxicity or impact response rate to TKIs for adjuvant or first-line osimertinib. Further study with randomized controlled design is warranted to verified such treatment modality. Funding Innovent Biologics (Suzhou) Co., Ltd. provided PD-1 regimen (sintilimab), participant compensation and insurance. This work was supported by National Science Foundation of China, Noncommunicable Chronic Diseases-National Science and Technology Major Project, National Natural Science Foundation of China National High-Level Talents Special Support Program, National Natural Science Foundation of China Major Joint Project on Key scientific issues of lung Cancer, Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer, Integrated Project of Major Research Plan of National Natural Science Foundation of China, National Health Commission Medical and Health Technology Development Research Centre Project.
Zhang et al. (Thu,) studied this question.