Health-Related Quality of Life in Advanced Non-small Cell Lung Cancer: A Methodological Appraisal Based on a Systematic Literature Review

Abstract

Background: The majority of lung cancer patients are diagnosed with advanced non-small cell lung cancer (NSCLC), the bulk of which receive palliative systemic treatment with the goal to provide effective symptom palliation and safeguard health-related quality of life (HRQoL). Advanced NSCLC trials with HRQoL endpoints face methodological constraints limiting interpretability. Objectives: We provide a comprehensive overview of recent clinical trials evaluating the impact of systemic therapies on HRQoL in advanced NSCLC, focusing on the methodological quality, with the ultimate goal to improve interpretation, comparison and reporting of HRQoL data. Methods: A systematic literature review was performed. Prospective studies published over the last decade evaluating the impact of systemic treatments on HRQoL in advanced NSCLC were included. Methodological quality of HRQoL reporting was assessed with the CONSORT-PRO extension. Results: Hundred-twelve manuscripts describing 85 trials met all criteria. No formal conclusion can be drawn regarding the impact on HRQoL of different treatments. We report an important variety in methodological quality in terms of definitions of HRQoL, missing data points, lack of standardization of analyzing and presenting HRQoL and no standard follow-up time. The quality of HRQoL data reporting varies substantially between studies but improves over time. Conclusion: This review shows that in the heterogeneous landscape of trials addressing HRQoL in advanced stage NSCLC. Methodology reporting remains generally poor. Adequate reporting of HRQoL outcome data is equally important to support clinical decision-making as to correctly inform health policy regarding direct approval and reimbursement of the new drugs and combinations that will come online.

Key Determinants of Health-Related Quality of Life Among Advanced Lung Cancer Patients: A Qualitative Study in Belgium and Italy

“… Bennett et al (2017) performed systematic review to explore the impact of SCLC on HRQL and the PROs used to capture this impact and conclude that paucity exists regarding the reporting on NSCLC HRQL outcomes. Likewise, Van Der Weijst et al (2019) performed a systematic literature review of clinical trials in NSCLC and conclude that while reporting HRQL data is important to support clinical decision-making as well as marketing authorisation and reimbursement decisions, the methodology of reporting HRQL remains poor. Among the instruments currently available to measure quality of life, primarily the EORTC QLQ-C30-LC13 ( EORTC, 2018 ), but also the Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale ( FACIT, 1995 ) and its LC specific subscale FACT-LCS ( FACT-LCS, 1995 ) are the most commonly used instruments in LC clinical trials ( HallSinghal et al, 2019 ; King-Kallimanis et al, 2019 ; Van Der Weijst et al, 2019 ).…”

“…Likewise, Van Der Weijst et al (2019) performed a systematic literature review of clinical trials in NSCLC and conclude that while reporting HRQL data is important to support clinical decision-making as well as marketing authorisation and reimbursement decisions, the methodology of reporting HRQL remains poor. Among the instruments currently available to measure quality of life, primarily the EORTC QLQ-C30-LC13 ( EORTC, 2018 ), but also the Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale ( FACIT, 1995 ) and its LC specific subscale FACT-LCS ( FACT-LCS, 1995 ) are the most commonly used instruments in LC clinical trials ( HallSinghal et al, 2019 ; King-Kallimanis et al, 2019 ; Van Der Weijst et al, 2019 ). Comparing our results to current LC specific scales (EORTC QLQ-C30-LC13 and FACT) reveals that the following side-effects and symptoms, observed in our study, are not included in all presently used HRQL specific LC scales: 1) skin conditions, 2) risk of infections, 3) sensory abnormalities, 4) increased weight, 5) autonomy/independence, 6) uncertainties regarding side-effects and (duration of) positive treatment outcomes, and 7) communication with healthcare providers.…”

“…With the emergence of innovative treatment modalities over the past decade, the LC treatment landscape has changed dramatically, with the range of options now extending beyond well-established therapies such as surgery, radiotherapy, and chemotherapy to include such new regimens such as targeted therapy, immunotherapy, and chemoimmunotherapy ( Dong et al, 2019 ; Remon et al, 2020 ). LC treatments in development and use today differ in terms of benefits (e.g., in terms of progression-free survival, overall survival, response rate, and long-term benefits), side-effects (e.g., pain, nausea, vomiting, breathing problems, fatigue, physical changes such as weight changes, bleeding, hair loss, and uncertain long-term safety), psychological impact (e.g., emotional distress, affective disorders), route of administration, and treatment schedule ( Dong et al, 2019 ; King-Kallimanis et al, 2019 ; Van Der Weijst et al, 2019 ; Remon et al, 2020 ).…”

Humanistic Burden of Living with Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: findings from the ALKConnect Patient Insight Network and Research Platform

“…These patient preference results are aligned with clinical trials that capture progression-free survival (PFS), objective response rates (ORR) and HRQoL. In addition to those clinical end points (PFS, ORR), which allow for assessment of the duration of tumor control and measurement of tumor shrinkage and tumor stabilization, HRQoL, a multi-dimensional concept, has become an integral end point in clinical trials for advanced cancer as it addresses the functional effect of a health status and/or a patient's treatment [28]. HRQoL-measured benefits have been shown to be consistent with the objective response benefits of ALK TKIs [29][30][31][32][33].…”

Real Life Data on Patient-Reported Outcomes and Neuro-Cognitive Functioning of Lung Cancer Patients: The PRO-Long Study

“…Therefore, the focus on the effect of treatment on wellbeing and functioning becomes increasingly important. It has been shown that lung cancer and its associated treatment indeed impacts health-related quality of life (HRQoL), they bring along several acute and late toxicities and may negatively affect neurocognitive functioning (6)(7)(8)(9).…”