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      Clinical Impact of Adherence to NCCN Guidelines for Biomarker Testing and First-Line Treatment in Advanced Non-Small Cell Lung Cancer (aNSCLC) Using Real-World Electronic Health Record Data

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          Abstract

          Introduction

          Although clinical guidelines are broadly available, the relationship between adherence and outcomes is not well studied. This study aimed to assess the association between adherence to National Comprehensive Cancer Network (NCCN) guidelines and clinical outcomes for adult patients with advanced non-small-cell lung cancer (aNSCLC).

          Methods

          This was a retrospective cohort study of adult patients with aNSCLC (stages IIIB, IIIC, and IV) from a de-identified real-world database. The objective was accomplished in a two-step analysis process. We first assessed adherence to NCCN recommendations for biomarker testing and overall survival (OS). Next, we assessed adherence to NCCN-recommended first-line therapy and time to treatment discontinuation (TTD). Multivariable Cox regression analyses were conducted to evaluate the association between guideline adherence and patient outcomes. Kaplan–Meier analyses were used to assess median OS and TTD.

          Results

          A total of 28,784 patients with a diagnosis for aNSCLC between January 1, 2011 and July 31, 2019 met the inclusion criteria for the analysis of NCCN-recommended biomarker testing adherence. Two-thirds of these patients ( n = 19,787) had evidence of biomarker testing (adherent). Multivariable Cox models found that testing-adherent patients had a significantly lower risk of mortality [hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.86, 0.92; p < 0.01]. Median OS was modestly longer in the testing-adherent group compared to the testing-non-adherent group (15.4 vs. 14.2 months; p < 0.01). For the first-line therapy analysis, 15,898 patients met the inclusion criteria, of which 69.9% had evidence of appropriate first-line therapy (first-line-adherent). The multivariable Cox model found that adherent patients had significantly lower risk of treatment discontinuation versus non-adherent patients (HR = 0.60, 95% CI 0.57, 0.62; p < 0.01). First-line-adherent patients had a modest, yet significantly longer median TTD compared to first-line-non-adherent patients (3.45 vs. 2.40 months; p < 0.01).

          Conclusions

          Improved clinical outcomes were observed in patients who were adherent to NCCN-recommended biomarker testing and first-line therapy. This study demonstrated the value of following NCCN guideline recommendations and the need to prioritize timely access to biomarker testing and individualized treatment.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s12325-020-01617-2.

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          Most cited references14

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          Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. clinicaltrials.gov Identifier: NCT01014286.
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              Therapy for Stage IV Non–Small-Cell Lung Cancer Without Driver Alterations: ASCO and OH (CCO) Joint Guideline Update

              The aim of this work is to provide evidence-based recommendations updating the 2017 ASCO guideline on systemic therapy for patients with stage IV non–small-cell lung cancer (NSCLC) without driver alterations. A guideline update for patients with stage IV NSCLC with driver alterations will be published separately. The American Society of Clinical Oncology and Ontario Health (Cancer Care Ontario) NSCLC Expert Panel made updated recommendations based on a systematic review of randomized controlled trials from December 2015 to 2019. This guideline update reflects changes in evidence since the previous guideline update. Five randomized controlled trials provide the evidence base. Additional literature suggested by the Expert Panel is discussed. Recommendations apply to patients without driver alterations in epidermal growth factor receptor or ALK. For patients with high programmed death ligand 1 (PD-L1) expression (tumor proportion score [TPS] ≥ 50%) and non–squamous cell carcinoma (non-SCC), the Expert Panel recommends single-agent pembrolizumab. Additional treatment options include pembrolizumab/carboplatin/pemetrexed, atezolizumab/carboplatin/paclitaxel/bevacizumab, or atezolizumab/carboplatin/nab-paclitaxel. For most patients with non-SCC and either negative (0%) or low positive (1% to 49%) PD-L1, the Expert Panel recommends pembrolizumab/carboplatin/pemetrexed. Additional options are atezolizumab/carboplatin/nab-paclitaxel, atezolizumab/carboplatin/paclitaxel/bevacizumab, platinum-based two-drug combination chemotherapy, or non–platinum-based two-drug therapy. Single-agent pembrolizumab is an option for low positive PD-L1. For patients with high PD-L1 expression (TPS ≥ 50%) and SCC, the Expert Panel recommends single-agent pembrolizumab. An additional treatment option is pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel). For most patients with SCC and either negative (0%) or low positive PD-L1 (TPS 1% to 49%), the Expert Panel recommends pembrolizumab/carboplatin/(paclitaxel or nab-paclitaxel) or chemotherapy. Single-agent pembrolizumab is an option in select cases of low positive PD-L1. Recommendations are conditional on the basis of histology, PD-L1 status, and/or the presence or absence of contraindications. Additional information is available at www.asco.org/lung-cancer-guidelines .
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                Author and article information

                Contributors
                ani.john@roche.com
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Cheshire )
                0741-238X
                1865-8652
                4 February 2021
                4 February 2021
                2021
                : 38
                : 3
                : 1552-1566
                Affiliations
                Roche Diagnostics, Santa Clara, CA USA
                Author information
                http://orcid.org/0000-0001-9309-7128
                Article
                1617
                10.1007/s12325-020-01617-2
                7932942
                33537872
                9b2efded-7ee6-41b5-9146-138e197fd3a9
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 25 November 2020
                : 23 December 2020
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare Ltd., part of Springer Nature 2021

                adherence,biomarker,first-line treatment,guidelines,non-small cell lung cancer,precision medicine

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