Ranjan Pathak1, Gilberto De Lima Lopes2, Han Yu3, Madan Raj Aryal3,4, Wenyan Ji3, Katherine Stemmer Frumento5, Christopher J D Wallis6, Zachary Klaassen7,8, Henry S Park9, Sarah B Goldberg1. 1. Division of Medical Oncology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut. 2. Department of Medical Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida. 3. Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, New York. 4. Department of Medicine (Medical Oncology), Roswell Park Comprehensive Cancer Center, Buffalo, New York. 5. Clinical Information Services, Harvey Cushing/John Hay Whitney Medical Library, Yale School of Medicine, New Haven, Connecticut. 6. Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee. 7. Division of Urology, Department of Surgery, Medical College of Georgia, Augusta University, Augusta, Georgia. 8. Georgia Cancer Center, Augusta University, Augusta, Georgia. 9. Department of Therapeutic Radiology, Yale School of Medicine, New Haven, Connecticut.
Abstract
BACKGROUND: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.
BACKGROUND: To the authors' knowledge, in the absence of head-to-head trials, it is unclear whether chemoimmunotherapy provides an additional overall survival (OS) benefit compared with immunotherapy alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors conducted a systematic literature review and network meta-analysis (NMA) to compare the efficacy of chemoimmunotherapy versus ICI. METHODS: MEDLINE, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from inception to April 2020. Phase 3 trials evaluating the efficacy of first-line ICI or chemoimmunotherapy and reporting efficacy outcomes (OS, progression-free survival [PFS], and the overall response rate [ORR]) stratified by programmed death-ligand 1 (PD-L1) status were included. NMA with a Bayesian random effects model was performed. RESULTS: A total of 12 eligible trials comprising 7845 patients were included. In patients who were negative for PD-L1 (tumor proportion score [TPS] <1%), NMA comparing chemoimmunotherapy with dual-agent ICI failed to demonstrate a statistically significant difference with regard to OS, PFS, or the ORR. In patients with low PD-L1 (TPS 1%-49%), there was no statistically significant difference observed between chemoimmunotherapy compared with either single-agent ICI or dual-agent ICI with regard to OS or the ORR. In patients with high PD-L1 (TPS ≥50%), chemoimmunotherapy was found to be associated with an improved PFS and ORR compared with single-agent ICI, but not with dual-agent ICI. No differences in OS were observed with chemoimmunotherapy when compared with either single-agent or dual-agent ICIs. CONCLUSIONS: Although chemoimmunotherapy appears to improve the ORR and PFS in patients with PD-L1-high tumors when compared with single-agent ICI, it does not appear to confer an OS benefit over single-agent or dual-agent ICI for patients with advanced NSCLC regardless of PD-L1 status. Prospective trials are needed to validate these findings.
Authors: Yizhen Guo; Lai Wei; Sandip H Patel; Gabrielle Lopez; Madison Grogan; Mingjia Li; Tyler Haddad; Andrew Johns; Latha P Ganesan; Yiping Yang; Daniel J Spakowicz; Peter G Shields; Kai He; Erin M Bertino; Gregory A Otterson; David P Carbone; Carolyn Presley; Samuel K Kulp; Thomas A Mace; Christopher C Coss; Mitch A Phelps; Dwight H Owen Journal: Clin Lung Cancer Date: 2022-01-08 Impact factor: 4.840