Contents lists available at ScienceDirect Lung Cancer journal homepage: www.elsevier.com/locate/lungcan Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018 Maria Lucia Reale a , Emmanuele De Luca b , Pasquale Lombardi c , Laura Marandino c , Clizia Zichi b , Daniele Pignataro a , Eleonora Ghisoni c , Rosario F. Di Stefano a , Annapaola Mariniello a , Elena Trevisi a , Gianmarco Leone a , Leonardo Muratori a , Anna La Salvia a,1 , Cristina Sonetto a,2 , Paolo Bironzo a , Massimo Aglietta c , Silvia Novello a , Giorgio V. Scagliotti a , Francesco Perrone d , Massimo Di Maio b, * a Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Orbassano, TO, Italy b Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Torino, Italy c Department of Oncology, University of Turin, Candiolo Cancer Institute - FPO- IRCCS, Candiolo, TO, Italy d Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori “Fondazione Giovanni Pascale”-IRCCS, Napoli, Italy ARTICLE INFO Keywords: Lung cancer Health-related quality of life Patient-reported outcomes Phase III trials Endpoints ABSTRACT Objectives: We previously reported that quality of life (QoL) is not included among trial endpoints and QoL results are underreported in a significant proportion of phase III oncology trials. Here we describe QoL adoption, reporting and methodology of QoL analysis in lung cancer trials. Materials and methods: We selected all primary publications of lung cancer phase III trials assessing anticancer drugs published between 2012 and 2018 by 11 major journals. Results: 122 publications were included. In 39 (32.0%) publications, QoL was not listed among endpoints: in 10/ 17 (58.8%) early stage/locally advanced NSCLC, in 15/54 (27.8%) first-line of advanced NSCLC; in 10/41 (24.4%) second and further lines of advanced NSCLC, in 4/10 (40.0%) SCLC. Proportion of trials not including QoL was similar over time: 32.9% publications in 2012–2015 vs. 30.6% in 2016–2018. Out of 83 trials including QoL among endpoints, QoL results were absent in 36 primary publications (43.4%). Proportion of trials without QoL results in primary publication increased over time (30.6% 2012–2015 vs. 61.8% 2016–2018, p = 0.005). Overall, QoL data were not available in 75/122 (61.5%) primary publications, due to the absent endpoint or unpublished results. QoL data were lacking in 48/68 (70.6%) publications of trials with overall survival as primary endpoint, 27/54 (50.0%) with other primary endpoints and 28/54 (51.9%) publications with a positive result. For trials including QoL among endpoints but lacking QoL results in primary publication, probability of secondary publication was 6.3%, 30.1% and 49.8% after 1, 2 and 3 years respectively, without evidence of improvement comparing 2012–2015 vs. 2016–2018. Conclusion: QoL is not assessed or published in many phase III lung cancer trials, a setting where QoL value should be highly considered, due to high symptom burden and generally limited life expectancy. Timely in- clusion of results in primary publications is worsening in recent years. 1. Introduction The treatment landscape of lung cancer is rapidly evolving, with an increasing number of therapeutic options and personalized approaches as never before. In the context of the precision medicine approach, lung cancer management takes into consideration, beyond staging and pa- tients’ clinical characteristics, also histology and molecular pathology with the identification of oncogenic driver alterations and other pre- dictive factors. Cytotoxic chemotherapy, usually platinum-based, the cornerstone of treatment for unselected patients for almost three https://doi.org/10.1016/j.lungcan.2019.10.022 Received 17 August 2019; Received in revised form 20 October 2019; Accepted 23 October 2019 ⁎ Corresponding author at: Department of Oncology, University of Turin, Division of Medical Oncology, Ordine Mauriziano Hospital, Via Magellano 1, Turin, 10128, Italy. E-mail address: massimo.dimaio@unito.it (M. Di Maio). 1 Present address: Department of Oncology, 12 de Octubre University Hospital, Madrid, Spain. 2 Present address: Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy. Lung Cancer 139 (2020) 47–54 0169-5002/ © 2019 Elsevier B.V. All rights reserved. T