Changes in Global Quality of Life after treatment with immune checkpoint inhibitors in patients with advanced stage lung cancer in the Netherlands – a 2015-2021 cohort study
Authors: Malhotra Ananya , Zepeda Erick S. , Vinke Petra C. , de Bock Geertruida H. , Maas Willemijn , Hiltermann T. Jeroen. N. , Rachet Bernard , Leyrat Clémence , Quaresma Manuela 
Published: April 2024

AbstractBackgroundIntroduction of immune checkpoint inhibitors (ICIs) has modified treatment modalities for patients with lung cancer, offering new alternatives for treatment. Despite improved survival benefits, ICIs may cause side-effects impacting patients’ quality of life (QoL). We aim to study the changes in global QoL (gQoL) up to 18 months of patients with advanced stage lung cancer after treatment with ICIs between 2015-2021.Methods and AnalysisA longitudinal cohort study was conducted using OncoLifeS data-biobank from the University Medical Center Groningen. Participants completed the EORTC QLQ-C30 questionnaire, at the beginning of their ICI treatment (baseline) and then at 6, 12 and 18 months. Using joint modelling, the predicted trajectory of gQoL was studied by treatment regimens up to 18 months, while accounting for the competing risk of death and adjusting for pre-specified covariates.ResultsOf 418 participants with median age 66 years, 39% were women. Patients receiving first line immuno-monotherapy with palliative intent had a small improvement ([5-8] points) in their gQoL within first six months, and no clinically significant change ([−5 to 5] points) thereafter, while patients with second/further line immunotherapy with palliative intent had no clinically significant change in their gQoL over 18 months. Patients receiving first line chemo-immunotherapy with palliative intent had a small improvement in their gQoL over 18 months, while patients receiving first line chemo-radiotherapy followed by Durvalumab with curative intent had no clinically significant change in their gQoL over 18 months.ConclusionThe differences in gQoL over time among patients with varying treatment regimens based on drug intensity, line and intent of treatment may help clinicians and patients understand the potential dynamic of treatments on QoL. It may further influence treatment decisions and patient management strategies, reflecting the practical implications of different treatment regimens.Key MessagesWhat is already known on this topicImmunotherapy has significantly helped in modifying treatment modalities for patients with advanced stage (stage 3 and 4) lung cancer, despite the unsatisfactory prognosis of this disease. In comparison to conventional therapies like chemotherapy, various trials reported more favourable outcomes in the health related QoL domain for patients who underwent treatment with immune checkpoint inhibitors (ICIs), which is a type of immunotherapy. Despite its benefits in terms of survival, longer time until deterioration in QoL and better control of symptoms after immunotherapy, ICIs may impact patients’ QoL due to its side-effects. However, such evidence has largely been drawn from clinical trials which not only have a strict eligibility criteria but also a relatively short follow-up of under one year, while treatment with immunotherapy may last up to two years. Although some patients with lung cancer achieve deep and durable responses with ICIs, not all patients benefit and develop side-effects which may impact their QoL.What this study addsThe main aim of this analyses was to study the changes in gQoL (measure by the European Organization for Research and Treatment of Cancer Quality of Life, EORTC QLQ-C30 questionnaire, version 3) over a period of 1.5 years after receiving treatment with ICIs for advanced stage lung cancer. Using joint models which account for the competing risk of death and adjusts for prespecified covariates such as baseline sociodemographic and clinical characteristics of the patients, we predicted and assessed the differences in the gQoL over time of patients who had different treatment regimens for their lung cancer diagnosis. Our analyses showed that patients receiving first line immuno-monotherapy with a palliative intent had a small improvement in their gQoL within first six months of ICI treatment, a trivial change up to one year and then a small deterioration thereafter, compared to patients with second/further line immunotherapy, who had a trivial change in their gQoL over 1.5 years after ICI treatment. Moreover, patients who had first line chemo-radiotherapy followed by Durvalumab with a curative intent had a small deterioration in their gQoL in first six months following ICI treatment, a trivial change up to one year and then a small improvement thereafter. Patients receiving first line chemo-immunotherapy with a palliative intent had a small improvement in their gQoL over 1.5 years. As a secondary outcome, we studied how the functional scores of patients change over 1.5 years, indicating their physical, social, emotional, role and cognitive wellbeing. While emotional, social and cognitive scores had trivial changes over time, physical and role functioning had a small deterioration over 1.5 years after ICI treatment.How this study might affect research, practice or policyThe differences in gQoL over time among patients with varying treatment regimens based on drug combination, line and intent of treatment may help guide clinicians and patients of potential benefits and impairments of treatments on QoL.