The efficacy and safety of neoadjuvant anti-PD-1 inhibitor combined with platinum-based chemotherapy in patients with potentially resectable non-small cell lung cancer.
Authors: Zhang Yongchang , Zeng Liang , Zhang Xiangyu , Zhou Yuling , Zhang Baihua , Jiang Wenjuan , Guo Lin , Wang Han , Gao Xuan , Guan Yan-Fang , Xia Xuefeng , Jiang Tao , Zhou Caicun , Yang Nong 
Published: June 2021

e20526 Background: Immunotherapy with anti-programmed death 1 (PD-1) antibodies has revolutionized the treatment of metastatic and advanced non-small cell lung cancer (NSCLC). However, its application in neoadjuvant scenario has not been well established. Here, we conducted a retrospective study to evaluate the efficacy and safety of neoadjuvant chemo-immunotherapy for patients with potentially resectable NSCLC. Methods: We retrospectively reviewed clinical records of patients with potentially resectable NSCLC (stage IIIA-IIIB) with non-driver gene mutation. The patients underwent neoadjuvant chemo-immunotherapy between March 2019 and October 2020. The outcomes included R0 resection rate, pathologic complete responses (pCR), major pathologic responses (MPR) and safety. The data of whole exome sequencing (WES) and RNA-sequencing (RNA-seq) from tumor samples respectively collected at baseline and at surgery after neoadjuvant therapy were also evaluated. Results: Out of a total of 30 stage III NSCLC patients (29 males and 1 female) at a median age of 56.5 years (range: 46-74), 22 patients (73.3%) had squamous cell carcinoma. Patients received toripalimab/pembrolizumab and platinum-doublet chemotherapy for 2 cycles before surgery. The median duration from final treatment to surgery was 31 days (range: 22-82). One patient refused surgery, and 6 patients did not meet the surgical standards. 23 patients (76.7%) downstaged and reached the surgical standards after neoadjuvant therapy. Out of 23 patients with R0 surgical resection, 16 patients (69.6%) achieved MPR, including 7 patients (30.4%) achieved pCR. The median follow-up duration was 13 months (range: 2-21). As of Jan 20, 2021, no patient had relapsed or died. All grade and grade 3-4 treatment-related adverse events (TRAEs) were reported in 43.3% and 10% of patients, respectively. The most common grade 1-2 TRAEs were transaminase increased (13.3%) and hypothyroidism (16.7%). One patient delayed surgical treatment due to grade 4 transaminase increased. Baseline expression of type-I HLA molecule was lower in MPR/pCR group than that in non-MPR group (HLA-F: p = 0.052). After neoadjuvant therapy, the expression of HLA-F in MPR/pCR patients was significantly increased (p = 0.0047) while the expression of HLA-B in non-MPR patients was decreased (p = 0.032) compared to that of the baseline, suggesting that neoadjuvant therapy may potentially facilitate specific antigen presentation in the tumor tissues of patients with MPR/pCR. Conclusions: Neoadjuvant chemo-immunotherapy for potentially resectable NSCLC is a tolerable treatment with an improved surgical resection rate, MPR and pCR. Based on our findings, a prospective, single arm, phase II study of neoadjuvant toripalimab combined with platinum-doublet chemotherapy is currently being conducted (NCT04144608). Clinical trial information: NCT04324151.