Quality of life analysis in lung cancer: A systematic review of phase III trials published between 2012 and 2018
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 patients’ clinical characteristics, also histology and molecular pathology with the identification of oncogenic driver alterations and other predictive factors. Cytotoxic chemotherapy, usually platinum-based, the cornerstone of treatment for unselected patients for almost three decades, is now challenged in many patients by targeted therapies and immune checkpoint inhibitors, and, in the near future, by chemo-immunotherapy [1]. Despite significant improvements in terms of treatment efficacy and tolerability, lung cancer, often diagnosed as advanced or metastatic disease, has a disappointing long term survival rate, remaining one of the first causes of cancer-related deaths among both men and women [2]. Progression free survival (PFS) often remains unsatisfying and, moreover, patients are generally symptomatic and clinically vulnerable.
In this context, the awareness of the real, overall treatment value is of crucial importance and is linked to patients’ subjective experience. Patient reported outcomes (PROs) are the self-measurement of the personal status of the patient, without any external interpretation, and represent a valid tool to assess subjective perception of disease burden and treatment impact, both in clinical trials and in daily clinical practice [3]. Health-related quality of life (QoL) is a specific and multidimensional type of PRO related to the physical, psychological and social impact of the disease and its treatment perceived by patients [4]. It is universally considered a measure of clinical benefit and a tool of achieving a global patient-centered treatment approach. Furthermore, QoL allows, together with data of efficacy and safety, allows a more complete assessment of risks and benefits of each treatment in clinical research and a more accurate patient-physician communication in daily practice.
In recent years, the most important scientific societies as the American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) have generated some framework schemes in order to define the value of anticancer treatments, incorporating QoL among the variables contemplated [[5], [6], [7], [8]].
In addition, regulatory agencies, both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have underlined the importance of QoL inclusion among the endpoints of clinical trials, highlighting the relevance of patient’s perspective as a standard outcome measure [[9], [10], [11]].
However, regardless the widely recognized importance of QoL evaluation, the attention to QoL results is still suboptimal. In a recent systematic review of randomized phase III trials testing anticancer drugs in all solid tumours, published by major journals between 2012 and 2016, we showed an alarming deficiency of QoL among endpoints. In particular, among the 446 publications identified, QoL was apparently not included as trial endpoint in 210 (47.1%). Even when QoL was present, data were significantly underreported, were not available in the majority of primary publications and were published with important delay compared to primary results [12].
Aim of this systematic review is to describe QoL adoption and reporting in randomized phase III trials testing anticancer drugs in lung cancer patients, published between 2012 and 2018 by 11 major journals. We analyzed QoL inclusion among endpoints, presence of QoL results, methodology of analysis and presentation of results.
Section snippets
Materials and methods
As reported before [12], we selected eleven major journals where most of cancer randomized phase III trials are generally published: three general medical journals (JAMA, Lancet and New England Journal of Medicine) and eight oncology journals (Annals of Oncology, British Journal of Cancer, Cancer, JAMA Oncology, European Journal of Cancer, Journal of Clinical Oncology, Journal of the National Cancer Institute and Lancet Oncology). We hand-searched all the issues of the journals listed above and
Study characteristics
Overall, 122 primary publications were included in the analysis (Supplementary Tables 1–4). Their main characteristics are detailed in Table 1. Seventy-three studies (59.8%) were published between 2012 and 2015 and forty-nine (40.2%) between 2016 and 2018. The three most represented journals were: Journal of Clinical Oncology (38 papers, 31.1%), Lancet Oncology (31 papers, 25.4%) and Annals of Oncology (14 papers, 18.8%).
Eighty studies (65.6%) were classified as profit trials and 42 (34.4%) as
Discussion
This systematic review demonstrates that QoL is not assessed in a relevant proportion of phase III trials evaluating lung cancer patients. Furthermore, QoL results are significantly under-reported, with a disappointing worsening in the timely inclusion of results in primary publications in the last years.
Lung cancer patients could consider symptom control and quality of life even more important than life prolongation [13]. However, our analysis shows a significant proportion of studies not
Conclusions
In conclusion, this analysis found that QoL is not assessed in a relevant proportion of phase III trials evaluating lung cancer patients, with significant under-reporting of QoL results in primary publications. Furthermore, timely inclusion of QoL results in primary publications is significantly worsening in last years, and this is particularly frequent in papers published in high impact factor journals. In the era of the precision medicine, however, PROs and QoL analyses could play a crucial
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of Competing Interest
Massimo Aglietta had roles as consultant or advisor for Roche, Bristol Myers Squibb, Merck and Co.; Silvia Novello declared a role as Speaker Bureau for Roche, Boeringer Ingelheim, Eli Lilly, Astra Zeneca, MSD; Giorgio Vittorio Scagliotti received honoraria, research funding and had roles as consultant or advisor for Roche, Pfizer, AstraZeneca, Lilly Pharma and MSD; Francesco Perrone received honoraria from Bayer, Daiichi Sankyo, Ipsen, AstraZeneca and Bristol Myers Squibb and received research
References (23)
- et al.
A standardised, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies: the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS)
Ann. Oncol.
(2015) - et al.
ESMO-magnitude of clinical benefit scale version 1.1
Ann. Oncol.
(2017) - et al.
Deficiencies in health-related quality-of-life assessment and reporting: a systematic review of oncology randomized phase III trials published between 2012 and 2016
Ann. Oncol.
(2018) - et al.
Lessons from clinical trials on quality-of-life assessment in ovarian cancer trials
Ann. Oncol.
(2016) Quality of life assessment using patient-reported outcome (PRO) measures: still a Cinderella outcome?
Ann. Oncol.
(2018)- et al.
Patient versus clinician symptom reporting using the National Cancer institute Common Terminology Criteria for Adverse Events: results of a questionnaire-based study
Lancet Oncol.
(2006) - et al.
Patient-reported outcome measures (PROMs) in the management of lung cancer: a systematic review
Lung Cancer
(2017) - et al.
An update on predictive biomarkers for treatment selection in non-small cell lung cancer
J. Clin. Med.
(2018) - et al.
Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods
Int. J. Cancer
(2019) Guidance for Industry Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims
(2009)
Reflection paper on the use of patient reported outcome measure in oncology studies. June 17
Cited by (0)
- 1
Present address: Department of Oncology, 12 de Octubre University Hospital, Madrid, Spain.
- 2
Present address: Gynecologic Oncology, IRCCS National Cancer Institute, Milan, Italy.