Schulz, Christian and Gandara, David and Berardo, Carmen G. and Rosenthal, Rachel and Foo, Jason and Morel, Chaienna and Ballinger, Marcus and Watkins, Claire and Chu, Paula (2019) Comparative Efficacy of Second- and Subsequent-line Treatments for Metastatic NSCLC: A Fractional Polynomials Network Meta-analysis of Cancer Immunotherapies. CLINICAL LUNG CANCER, 20 (6). 451-+. ISSN 1525-7304, 1938-0690
Full text not available from this repository. (Request a copy)Abstract
Cancer immunotherapies have advanced the second-line treatment of non-small-cell lung cancer. Evaluating the relative effect of these therapies requires methods accounting for the delayed clinical effect and longer-term survival rates that have been observed in anti-programmed death-ligand 1/programmed cell death protein 1 therapy trials. This study applied advanced statistical methods to compare clinical trial results across all second-line treatments. The immunotherapies offered superior efficacy in non-small-cell lung cancer. Background: Extended onset of treatment effect and longer-term survival with antieprogrammed death-ligand 1 (PDL1)/programmed cell death protein 1 (PD-1) immunotherapies, atezolizumab, nivolumab, and pembrolizumab, have changed the landscape of second- or subsequent-line (2L+) treatments for adults with non-small-cell lung cancer (NSCLC). This systematic literature review included phase I to IV randomized, controlled trials of 2L+ NSCLC therapies from MEDLINE, Embase, and secondary sources. Materials and Methods: Studies of treatments approved in the European Union or United States had to be in English with >= 10 patients per arm. A fractional polynomials network meta-analysis (NMA) was conducted because traditional NMA of hazard ratios does not account for delayed onset of clinical effect or long-term survival observed in PD-L1/PD-1 inhibitor trials. Adjusted analyses accounted for treatment switching in the atezolizumab OAK trial. Expected survival time reflected area under the curve over the time horizon. Expected overall survival (OS) was ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve. Of 25,115 screened records, 28 studies were included in the quantitative analyses of OS and progression-free survival. Results: PD-L1/PD-1 inhibitors had comparable expected 5-year OS; all performed better than other treatment options. In unadjusted analyses, surface under the cumulative ranking curve ranked nivolumab first (87.9%), followed by atezolizumab (85.8%) and pembrolizumab (82.8%). Analyses adjusted for patients switching from docetaxel to immunotherapy ranked atezolizumab first (89.6%), followed by nivolumab (86.5%) and pembrolizumab (81.9%). Conclusion: This NMA applied an appropriate approach for indirect comparisons, including cancer immunotherapies, and supported robustness of PD-L1/PD-1 immunotherapies for 2L+ treatment of NSCLC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CELL LUNG-CANCER; RANDOMIZED PHASE-III; 2ND-LINE TREATMENT; DOUBLE-BLIND; OPEN-LABEL; WEEKLY DOCETAXEL; WILD-TYPE; ERLOTINIB; TRIAL; CHEMOTHERAPY; Atezolizumab; Nivolumab; Overall survival; Pembrolizumab; Programmed cell death 1 ligand 1 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 14:00 |
| Last Modified: | 24 Mar 2020 14:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25917 |
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