1160P Efficacy and biomarker identification of neoadjuvant chemo-immunotherapy in potentially resectable non-small cell lung cancer

Abstract

Treatment combination of immune checkpoint inhibitor (ICI) and platinum-based chemotherapy brought benefits for stage IIIA-IIIB non-small cell lung cancer (NSCLC) patients. This study evaluated the therapeutic feasibility of PD-1 plus platinum-doublet chemotherapy for potentially resectable NSCLC. We retrospectively collected demographic and treatment data of potentially resectable NSCLC patients treated with neoadjuvant chemo-immunotherapy (toripalimab/pembrolizumab, etc.) between Mar 2019 and Jan 2021. Inclusion criteria: stage IIIA-IIIB, non-driver gene mutation, complete medical record and ECOG 0-1. A total of 56 patients (median age: 58, IQR: 46-74; female: 2, 3.6%) were enrolled, including 47 (83.9%) with squamous cell carcinoma and 15 (26.8%) with stage IIIB disease. Six patients refused surgery and 5 did not qualify. A total of 45 (80.4%) patients underwent surgery, all with R0. Before surgery, patients received a median of 2 doses. The interval between neoadjuvant therapy last dose and surgery was 35 days. Among the 45 evaluated patients, 31 (68.9%) achieved major pathological response (MPR), 18 (40.0%) had pathological complete response (pCR), while 37 (82.2%) had pathological downstaging and none had surgical complications. The median follow-up was 11 (IQR: 2-27) months. On April 18, 2021, 3 patients relapsed. All Grade (G) treatment-related AEs (TRAEs) occurred in 33 patients (33/56). G ≥ 3 TRAEs were found in 3 patients (1 immune enteritis; 1 alanine aminotransferase increase; 1 pneumonia). Two patients delayed surgery following increased G3 alanine aminotransferase and G2 myocarditis. MPR or pCR patients had significantly lower baseline expression of SPRR3 (p = 3.93*10ˆ-7), KRT4 (p = 4.83*10ˆ-15), KRT13 (p = 4.82*10ˆ-09), ADAMTS20 (p = 6.92*10ˆ-10) and SERPINA3 (p = 2.68*10ˆ-10). For irAE patients, ERBB2 (p = 0.038), MDK (p = 0.015) and MUC16 (p = 0.0018) expression baselines were significantly lower while those of complement component 2 paralog (p = 3.21*10ˆ-15) and PIWIL1 (p = 0.026) were higher than non-irAE patients. ICI and platinum-doublet chemotherapy for potentially resectable NSCLC is effective and tolerable.