Association Between PDL1 Genetic Variation and Efficacy of Apatinib Monotherapy in Patients with Previously Treated Advanced NSCLC: A Real-World Retrospective Study

Abstract

Background This study aimed to explore associations between PDL1 polymorphisms and efficacy of apatinib for patients with previously treated advanced non–small cell lung cancer (NSCLC) in a real-world setting. Methods We retrospectively recruited 148 patients with previously treated advanced NSCLC from January 2015 to December 2019 continuously. Clinical efficacy in patients receiving apatinib treatment was evaluated. Adverse reactions were documented during treatment. Biological specimens of peripheral blood and cancer tissue biopsies were obtained for the genotyping of genetic variations in PDL1 and corresponding gene-mRNA expression, respectively. Univariate association analysis between the status of PDL1 genetic variations and survival was performed with Kaplan–Meier survival analysis. Results The objective response rate of the 148 patients was 17.6% and disease-control rate 68.9%. Prognostic data suggested that median progression-free survival (PFS) was 3.8 (95% CI 3.13–4.47) months and median overall survival (OS) 10.5 (95% CI 9.06–11.95) months. Regarding PDL1 genetic variation, only rs2297136 was of clinical significance. Prognosis analysis revealed that PFS and OS for the rs2297136 genotype were significantly different. Median PFS of patients with TC/CC and TT genotypes was 3 and 4.5 months, respectively ( P =0.006). Median OS of the two genotypes was 9 and 11.6 months, respectively ( P =0.04). Furthermore, the safety profile suggested that the most common adverse reactions were hypertension, dermal toxicity, fatigue, and oral toxicity. This study failed to find any significant association between adverse reactions and rs2297136. Interestingly, mRNA-expression analysis demonstrated that mRNA expression of PDL1 in biopsy cancer–tissue specimens was significantly different based on rs2297136-genotype status ( P <0.001). Conclusion The PDL1 polymorphism rs2297136 could be used as a potential biomarker for the prognosis of patients with NSCLC receiving apatinib monotherapy.

Efficacy and Safety of Anlotinib Monotherapy as Third-Line Therapy for Elderly Patients with Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…To our knowledge, management of the patients and adherence of the therapy in a retrospective study was not sufficient and normative compared with the well-designed phase III clinical trial, which was proved in another retrospective study. 28 A third reason could be attributed to the fact that patients with ECOG 2 score in our study accounted for a much higher proportion than those in the ALTER0303 trial (53.0% versus 0.7%). To our knowledge, ECOG performance status was confirmed to be an independent prognostic factor to predict the survival among patients with NSCLC.…”

Effectiveness and Safety of PD-1 Inhibitor Monotherapy for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Real-World Exploratory Study

“…Furthermore, our study was designed as a retrospective analysis. Management of the patients in the retrospective study was not sufficient and normative compared with a well-designed clinical trial, thus deteriorating the efficacy and prognosis in our study to some extent, which was also proved by the previous retrospective study among patients with advanced NSCLC [30]. e above three aspects might be the potential reasons why the median PFS in our study is inferior to that in the Keynote-010 study.…”

A Genetic Variant in CD274 Is Associated With Prognosis in Metastatic Colorectal Cancer Patients Treated With Bevacizumab-Based Chemotherapy

“…This gene encodes PD-L1, which is an immune inhibitory receptor ligand that is expressed by hematopoietic and non-hematopoietic cells, such as T cells and B cells and various types of tumor cells (25). Hu et al reported that in advanced non-small cell lung cancer (NSCLC) patients receiving apatinib treatment, patients with TT(AA) genotype of CD274:rs2297136 had a significantly longer median PFS and OS than patients with any C(G) allele (26). As apatinib is also an antiangiogenic drug, our study and theirs both support the link between AA genotype of CD274:rs2297136 and a favor response to antiangiogenic therapy.…”

“…Hu et al. reported that in advanced non-small cell lung cancer (NSCLC) patients receiving apatinib treatment, patients with TT(AA) genotype of CD274 :rs2297136 had a significantly longer median PFS and OS than patients with any C(G) allele ( 26 ). As apatinib is also an antiangiogenic drug, our study and theirs both support the link between AA genotype of CD274 :rs2297136 and a favor response to antiangiogenic therapy.…”