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Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer.

ABSTRACT: A network meta-analysis evaluating efficacy and adverse events of eight erlotinib-based therapies (erlotinib+placebo, erlotinib+tivantinib, erlotinib+celecoxib, erlotinib+onartuzumab, erlotinib+sunitinib, erlotinib+entinostat, erlotinib+sorafenib, and erlotinib+bevacizumab) for advanced/metastatic non-small-cell lung cancer (NSCLC) was performed. PubMed and Cochrane Library were reviewed, and ten randomized controlled trials were identified in which patients receiving at least one erlotinib-based therapy. Efficacy outcomes, including progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR), and adverse outcomes were evaluated. Patients treated with erlotinib+tivantinib, or erlotinib+celecoxib had longer PFS than patients on erlotinib+placebo; patients on erlotinib+tivantinib had longer OS compared to erlotinib+placebo. For PFS, erlotinib+celecoxib had the highest value of surface under the cumulative ranking curve (SUCRA). For OS, erlotinib+tivantinib had the highest SUCRA. For ORR, erlotinib+bevacizumab had the highest SUCRA, while erlotinib+entinostat ranked the lowest. For DCR, erlotinib+sorafenib had the highest SUCRA. Erlotinib+onartuzumab had the highest SUCRA for diarrhea, nausea, vomiting, decreased appetite, and dyspnea. Erlotinib+sunitinib had the lowest SUCRA for diarrhea, nausea, vomiting, and decreased appetite. Erlotinib + entinostat had the lowest SUCRA for fatigue, asthenia, and dyspnea. Our study suggests erlotinib+tivantinib and erlotinib+celecoxib regimens have the best long-term efficacy, while erlotinib+sunitinib and erlotinib+entinostat have the fewest adverse effects in patients with advanced/metastatic NSCLC.

SUBMITTER: Li F

PROVIDER: S-EPMC5689727 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer.

Li Fei F Zhang Shu-Hua SH Pang Li-Min LM

Oncotarget 20170731 49

A network meta-analysis evaluating efficacy and adverse events of eight erlotinib-based therapies (erlotinib+placebo, erlotinib+tivantinib, erlotinib+celecoxib, erlotinib+onartuzumab, erlotinib+sunitinib, erlotinib+entinostat, erlotinib+sorafenib, and erlotinib+bevacizumab) for advanced/metastatic non-small-cell lung cancer (NSCLC) was performed. PubMed and Cochrane Library were reviewed, and ten randomized controlled trials were identified in which patients receiving at least one erlotinib-base ...[more]

PMID: 29156837

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Project description:PurposeImmune-mediated adverse events (imAEs) may be associated with response to immune checkpoint inhibitors. We assessed the relationship between imAE development and efficacy in metastatic non-small-cell lung cancer patients treated with durvalumab (anti-programmed cell death ligand-1 [PD-L1]) alone or in combination with tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4).MethodsThe analysis used individual patient-level data from 307 and 310 patients in the monotherapy and combination arms of MYSTIC, respectively. We evaluated the association between treatment efficacy and development of imAEs using univariate and multivariate survival analyses. Using machine learning, we built a predictive model utilizing baseline clinical and laboratory features to identify patients at risk of developing imAEs and further evaluated patient survival based on a threshold index extracted from the model.ResultsPatients who developed any grade of imAE had improved overall survival versus patients without (hazard ratio [HR] 0.51; 95% confidence interval [CI]: 0.41-0.62). imAE development was associated with improved overall survival (HR 0.54; 95% CI 0.44-0.66) in a multivariate Cox proportional hazard model considering patient demographic features and baseline characteristics. Higher odds of imAE development were observed (odds ratio 3.023; 95% CI: 1.56-5.83) in responders versus non-responders in patients treated with immunotherapy. Based on baseline characteristics, the random forest classification algorithm was used to formulate a predictive model to identify patients at increased risk of developing imAEs during treatment.ConclusionPost-hoc exploratory analysis found that the efficacy of immunotherapy was improved in patients who developed on-treatment imAEs. This was independent of severity of imAEs or the need for steroid treatment, which is important in allowing patients to remain on treatment and derive optimal clinical benefit. Further research is warranted to establish the correlation between incidence of imAEs and efficacy in this patient population.

Dataset Information

Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer.

Publications

Meta-analysis of efficacy and adverse events of erlotinib-based targeted therapies for advanced/metastatic non-small cell lung cancer.

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