Efficacy and Biomarkers of Advanced Non-small Cell Lung Carcinoma (NSCLC) Patients Receiving Different PD-1 Agents in Northern China: A Real-world Clinical Study

Abstract

Aim and Methods: From May 2019 to January 2020, 116 advanced NSCLC patients with programmed death ligand-1 (PD-L1) expression > 1% were treated with nivolumab (44), pembrolizumab (21), and toripalimab (51) as a mono-therapy, respectively. The primary endpoints were defined as the objective response rate (ORR) after 3 and 6 months of therapy, and the progression-free survival (PFS). The observed efficacy of the different PD-1 antibodies was also compared. The gene mutation statuses of tumor protein p53 (TP53), epidermal growth factor receptor ( EGFR ), and anaplastic lymphoma kinase ( ALK ), the tumor mutational burden (TMB), along with the expression of CD47 were analyzed.Results: Toripalimab had a higher ORR and a longer PFS than the other two PD-1 agents after 3 months of evaluation (P = 0.0178). Thenon-classical mutations of EGFR (EGFRG719C and EGFRE709V) did not significantly influence the efficacy of the PD-1 inhibitors, while TP53 mutation, high TMB and elevated PD-L1 expression showed benefits. EGFR co-mutated genes were enriched in the “Response to osmotic stress” , “response to oxidative stress” and “myeloid leukocyte activation” pathways. CD47 expression showed a negative correlation to the prognosis of anti-PD-1 therapy. Participants with ALK rearrangement exhibited poor clinical outcomes. Conclusions: Toripalimab seemed to have a more rapid effect and provide a longer PFS than pembrolizumab and nivolumab. The PD-1 blockade therapy was benefited by TP53 mutation, high TMB, and elevated PD-L1 expression. CD47 expression is a potential biomarker to predict the efficacy of PD-1 blockade treatment in patients with EGFR mutations.Clinical Trail : Real-World Study of Four PD-1 Agents in China(May/22/2019)Trial Registration number: NCT03966456 URL:https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0008Y4C&selectaction=Edit&uid=U00045OC&ts=3&cx=z2uldc