PMID- 33585195 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220420 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 10 DP - 2020 TI - Efficacy and Safety of PD-1/PD-L1 Inhibitors Plus Chemotherapy Versus PD-1/PD-L1 Inhibitors in Advanced Non-Small Cell Lung Cancer: A Network Analysis of Randomized Controlled Trials. PG - 574752 LID - 10.3389/fonc.2020.574752 [doi] LID - 574752 AB - Immune checkpoint inhibitors (ICIs) are recommended as first-line treatment for late-stage non-small cell lung cancer (NSCLC), either as monotherapy or in combination with chemotherapy. However, efficacy and safety comparisons between ICIs as monotherapy and ICIs with chemotherapy are lacking. We searched PubMed, Embase, and Cochrane Library for randomized controlled trials published before February 29th, 2020, with the search terms "immunotherapy" and "chemotherapy". 10 eligible trials were identified with a total of 5,956 patients. Of these patients, 3,204 received immune therapy and 2,752 received chemotherapy. PD-1 inhibitors with chemotherapy improved OS (HR 0.84, 0.77-0.92), PFS (HR 0.80, 0.75-0.85), and objective response rate (ORR) (odds ratio (OR) 2.55, 1.20-5.28) compared to PD-1 inhibitors as monotherapy. In contrast, PD-L1 inhibitors plus chemotherapy showed no significant differences in OS, PFS, or ORR compared with PD-L1 inhibitors as monotherapy. When patients were stratified according to PD-L1 expression level, patients with high PD-L1 expression (>/= 50%) receiving PD-1 inhibitors plus chemotherapy had improved PFS, but not other outcomes, compared to PD-1 inhibitors as monotherapy. In these patients, PD-L1 inhibitors plus chemotherapy showed no significant difference in survival compared with PD-L1 inhibitors. In the low PD-L1 expression group (1%-49%), PD-1 inhibitors plus chemotherapy improved OS and PFS, but no advantage was observed in PD-L1 inhibitors plus chemotherapy in OS, PFS, or ORR compared with PD-L1 inhibitor monotherapy. When comparing PD-1/PD-L1 inhibitors plus chemotherapy with PD-1/PD-L1 inhibitors monotherapy, no significant differences were observed in the rate of immune-related adverse events (AEs). In summary, for treating patients with late-stage NSCLC, PD-1 inhibitors plus chemotherapy have improved efficacy compared with PD-1 inhibitor monotherapy, but PD-L1 inhibitors plus chemotherapy have similar efficacy as PD-L1 monotherapy. Survival benefits of PD-1/PD-L1 inhibitors combined with chemotherapy were particularly significant in patients with low PD-L1 expression levels. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42020166678 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=166678). CI - Copyright (c) 2021 Li, Yan, Yang, Wang, Lv, Li, Zhao, Yang, Zhuo and Wu. FAU - Li, Xiang AU - Li X AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yan, Shi AU - Yan S AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yang, Jichun AU - Yang J AD - Central Laboratory, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Wang, Yaqi AU - Wang Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Lv, Chao AU - Lv C AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Li, Shaolei AU - Li S AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhao, Jun AU - Zhao J AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Yang, Yue AU - Yang Y AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Zhuo, Minglei AU - Zhuo M AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, Beijing, China. FAU - Wu, Nan AU - Wu N AD - Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing, China. LA - eng PT - Systematic Review DEP - 20210111 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC7873939 OTO - NOTNLM OT - PD-1/PD-L1 inhibitors OT - PD-L1 expression level OT - first line treatment OT - late-stage non-small cell lung cancer OT - safety OT - survival efficacy COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/02/16 06:00 MHDA- 2021/02/16 06:01 PMCR- 2020/01/01 CRDT- 2021/02/15 06:10 PHST- 2020/06/21 00:00 [received] PHST- 2020/11/23 00:00 [accepted] PHST- 2021/02/15 06:10 [entrez] PHST- 2021/02/16 06:00 [pubmed] PHST- 2021/02/16 06:01 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2020.574752 [doi] PST - epublish SO - Front Oncol. 2021 Jan 11;10:574752. doi: 10.3389/fonc.2020.574752. eCollection 2020.