Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC

Abstract

Introduction: Programmed death receptor-1 (PD-1) inhibitors have shown efficacy in first-line treatment of NSCLC; however, evidence of PD-1 inhibitor as neoadjuvant treatment is limited. This is a phase 1b study to evaluate the safety and outcome of PD-1 inhibitor in neoadjuvant setting. Methods: Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 out of 22). Operation was performed between day 29 and 43. Positron emission tomographycomputed tomography scans were obtained at baseline and before the operation. The primary end point was safety. Efficacy end points included rate of major pathologic response (MPR) and objective response rate. Expression of programmed cell death ligand 1 was also evaluated (registration number: ChiCTR-OIC-17013726). Results: A total of 40 patients enrolled, all of whom received two doses of sintilimab and 37 underwent radical resection. A total of 21 patients (52.5%) experienced neoadjuvant treatment-related adverse events (TRAEs). Four patients (10.0%) experienced grade 3 or higher neoadjuvant TRAEs, and one patient had grade 5 TRAE. Eight patients achieved radiological partial response, resulting in an objective response rate of 20.0%. Among 37 patients, 15 (40.5%) achieved MPR, including six (16.2%) with a pathologic complete response in primary tumor and three (8.1%) in lymph nodes as well. Squamous cell NSCLC exhibited superior response compared with adenocarcinoma (MPR: 48.4% versus 0%). Decrease of maximum standardized uptake values after sintilimab treatment correlated with pathologic remission (p < 0.00001). Baseline programmed cell death ligand 1 expression of stromal cells instead of tumor cells was correlated with pathologic regression (p ¼ 0.0471).

Emerging Therapies in Thoracic Malignancies—Immunotherapy, Targeted Therapy, and T-Cell Therapy in Non–Small Cell Lung Cancer

“…These results overall are similar to the MPR after 3 cycles of nivolumab in the phase 2 randomized NEOSTAR ( NCT03158129 ) trial, 20 which demonstrated MPR of 17% in 23 treated patients. In another neoadjuvant study evaluating PD-1 inhibitor sintilimab in resectable NSCLC, 2 doses of neoadjuvant ICB induced 40.5% MPR rate, 21 which is similar to the results of phase I study MK3475-223 ( NCT02938624 ) 22 with pembrolizumab (MPR 40%). Although there is a clear intertrial variability in terms of MPR rates after ICB monotherapy, which may be driven by several variables, including the type of immunotherapy, tumor histology, oncogenic drivers, and perhaps number of doses prior to surgery, it appears that neoadjuvant anti–PD-1/PD-L1 therapy is overall safe and feasible and its efficacy appears to be very similar or slightly better than platinum doublet chemotherapy.…”

Lung Cancer in People’s Republic of China

“…In recent years, new therapeutic combinations of surgery with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been attracting wide attention and have been found to have encouraging results in (neo)adjuvant applications. 16,17 Surgery is not routinely used in the management of stage IV cancer, although it can be considered in patients who present with resectable oligometastatic lesions and well-controlled primary tumors. The proportion of surgery of metastatic lesions to total surgery volume is not high (less than 10%) in big hospitals but brings substantial survival benefit for eligible patients with advanced-stage disease.…”

Biomarkers or factors for predicting the efficacy and adverse effects of immune checkpoint inhibitors in lung cancer: achievements and prospective

“…[ 15 ] Notably, studies have reported success in the application of sintilimab as a neoadjuvant therapy for NSCLC patients. [ 16 ] Atezolizumab has been approved as a second-line treatment in patients with advanced stages of NSCLC based on the results of several clinical trials. Previous studies have reported that the high efficacy of atezolizumab is associated with the high expression levels of PD-L1.…”