Monica Khunger1, Prantesh Jain2, Sagar Rakshit1, Vinay Pasupuleti3, Adrian V Hernandez4, James Stevenson5, Nathan A Pennell5, Vamsidhar Velcheti6. 1. Department of Internal Medicine, Cleveland Clinic, Cleveland, OH. 2. Department of Hospital Medicine, Cleveland Clinic, Cleveland, OH. 3. ProEd Communications Inc, Cleveland, OH. 4. University of Connecticut/Hartford Hospital Evidence-Based Practice Center, Hartford, CT; School of Medicine, Universidad Peruana de Ciencias Aplicadas, Lima, Peru. 5. Department of Hematology and Oncology, Tausig Cancer Institute, Cleveland Clinic, Cleveland, OH. 6. Department of Hematology and Oncology, Tausig Cancer Institute, Cleveland Clinic, Cleveland, OH. Electronic address: velchev@ccf.org.
Abstract
INTRODUCTION: Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Objective response rate (ORR) and progression-free survival (PFS) data were collected and combined using DerSimonian and Laird random effects model meta-analysis. The I2 statistic was used to assess heterogeneity. RESULTS: Seventeen distinct trials (8 with treatment-naive patients [n = 937]; 14 with chemotherapy-treated patients [n = 3620]; 5 with separate treatment-naive and previously treated arms) were included. Treatment-naive patients had a statistically significant higher ORR (30.2%; 95% confidence interval [CI], 22.70-38.2) than patients previously treated with chemotherapy (ORR, 20.1%; 95% CI, 17.5-22.9; P = .02). No significant differences in PFS were observed between the 2 groups. Treatment-naive patients had statistically significant higher rates of all grade pneumonitis compared with previously treated patients (4.9%; 95% CI, 3.4-6.7 vs. 3.0%; 95% CI, 2.0-4.1; P = .04); however, no significant differences in any other immune-related adverse events were observed. CONCLUSION: PD-1/PD-L1 inhibitor therapy for advanced NSCLC has a significantly higher ORR and a higher rate of immune-mediated pneumonitis when used in the first-line setting compared with chemotherapy treated patients.
INTRODUCTION:Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small-cell lung carcinoma (NSCLC). However, there is a relative lack of data on comparative efficacy of these drugs in the first-line setting versus chemotherapy-treated patients. We compared the efficacy and toxicity of these drugs in these 2 distinct groups of patients. MATERIALS AND METHODS: Electronic databases (PubMed-Medline, EMBASE, Scopus) and major conference proceedings were systematically searched for all phase I to III clinical trials in NSCLC using PD-1/PD-L1 inhibitors. Objective response rate (ORR) and progression-free survival (PFS) data were collected and combined using DerSimonian and Laird random effects model meta-analysis. The I2 statistic was used to assess heterogeneity. RESULTS: Seventeen distinct trials (8 with treatment-naive patients [n = 937]; 14 with chemotherapy-treated patients [n = 3620]; 5 with separate treatment-naive and previously treated arms) were included. Treatment-naive patients had a statistically significant higher ORR (30.2%; 95% confidence interval [CI], 22.70-38.2) than patients previously treated with chemotherapy (ORR, 20.1%; 95% CI, 17.5-22.9; P = .02). No significant differences in PFS were observed between the 2 groups. Treatment-naive patients had statistically significant higher rates of all grade pneumonitis compared with previously treated patients (4.9%; 95% CI, 3.4-6.7 vs. 3.0%; 95% CI, 2.0-4.1; P = .04); however, no significant differences in any other immune-related adverse events were observed. CONCLUSION:PD-1/PD-L1 inhibitor therapy for advanced NSCLC has a significantly higher ORR and a higher rate of immune-mediated pneumonitis when used in the first-line setting compared with chemotherapy treated patients.
Authors: Ti Wen; Whitney Barham; Ying Li; Henan Zhang; Joanina K Gicobi; Jacob B Hirdler; Xin Liu; Hyoungjun Ham; Kodi E Peterson Martinez; Fabrice Lucien; Roxane R Lavoie; Hu Li; Cristina Correia; Dileep D Monie; Zesheng An; Susan M Harrington; Xiaosheng Wu; Ruifeng Guo; Roxana S Dronca; Aaron S Mansfield; Yiyi Yan; Svetomir N Markovic; Sean S Park; Jie Sun; Hong Qin; Minetta C Liu; George Vasmatzis; Daniel D Billadeau; Haidong Dong Journal: Cancer Immunol Res Date: 2021-12-15 Impact factor: 11.151