Short summary

The LIFE study (Lung cancer, Immunotherapy, Frailty, Effect) investigates lung cancer patients (non-small cell) treated with immunotherapy (immune check point inhibition). By mapping patient and disease characteristics of these real life patients including potentially frail patients, we investigate effect and toxicity in the everyday NSCLC patient. We will explore potential new biomarkers as well as investigate the Quality of Life in these patients - which will hopefully contribute to optimized treatment courses for those NSCLC patients to come.

Rationale

Lung cancer is the most lethal cancer diagnosis in Denmark and worldwide. Immune checkpoint inhibition (hereafter referred to as immunotherapy) has in recent years been approved for patients in good performance status (PS) with incurable advanced or metastatic non-small-cell-lung cancer (NSCLC), due to an improved overall survival (OS).

Immune checkpoint inhibitors are monoclonal antibodies (anti-PD-L1 or anti-PD-1) targeting Programmed Death-Ligands, which normally suppresses the immune system in order to control autoimmune reactions. When checkpoint inhibitors bind to their ligand site, they modulate the immune system, thereby allowing the immune system to kill cancer cells making long-lasting clinical responses possible.  The adverse effects of immunotherapy known as immune related adverse events (irAE) are treatment induced autoimmunity such as pneumonitis, hypophysitis, arthritis, thyroiditis etc. and the distribution and impact of irAE in real life patients are only sparsely investigated.

However, unlike the patients participating in the pivotal clinical trials, a large proportion of incurable NSCLC patients seen in every day practice have a poorer clinical status. This may be due to a combination of more comorbidity, higher age, more widespread disease (including brain metastasis) and poorer performance status (PS) at baseline.

 It is of great importance to study if unselected real life NSCLC patients, who might be less physically fit benefit from immunotherapy similarly to those in good PS without the addition of more immune related adverse events (irAE).  This study is performed in order to provide evidence of the effect and level of toxicity to treatment with immunotherapy in an unselected NSCLC patient population including less investigated subgroups.

Substudies investigating parameters described below will be performed:

Biomarkers

PD-L1 expression is presently the only biomarker used in the daily clinic for selecting NSCLC patients for immunotherapy. More biomarkers are needed. This study will investigate the potential of future biomarkers including circulating tumor DNA (cDNA) and measurements of pro- and anti-inflammatory cytokines as mediators of effect and immune related adverse effects. 

Comorbidity and morbidity

The study will both retrospectively and prospectively investigate the impact of comorbidityand in a prospective cohort investigate the Quality of Life in an unselected NSCLC population.

All in all:

This study will provide more clinically applicable data the effect, toxicity and QoL in real life NSCLC patients undergoing immunotherapy.  This is most warranted and important to obtain now because combinations of immunotherapy with other oncologic modalities is increasingly used as standard therapies. This might increase the level of toxicity especially in those NSCLC patients who are most vulnerable.

Description of the cohort

The cohort is based on a retrospective cohort of around 120 patients and a prospective cohort of 150 patients. All diagnosed with incurable advanced/metastatic NSCLC patients (recurrent disease, progressive disease or newly diagnosed disease) All expected to be included at the Odense University Hospital.

Data and biological material

Blood samples are gathered at baseline and consecutively during treatment with immunotherapy and at follow-up. QoL questionnaires are also performed consecutively in the prospective part of the study.  

Collaborating researchers and departments

Department of Oncology, Odense University Hospital

• Head of research, Professor Henrik Ditzel, DMSc,
• Associate Professor Tine Schytte, PhD, MD,
• Consultant Karin Holmskov Hansen, MD
• Trine Lembrecht Jørgensen, PhD, Postdoc, MD

Department of Clinical Oncology, Zealand, University Hospital Roskilde, Denmark

• Head of Research Professor Jørn Herrstedt, DMSci

Department of Clinical Biochemistry,  Odense University Hospital

• Consultant Mads Nybo, MD, PhD

Department of Radiology,  Odense University Hospital

• Consultant Jon Thor Asmussen

Publications associated with the project

Bjørnhart B, Hansen K, Jørgensen T, Herrstedt J, Schytte T. Efficacy and safety of immune checkpoint inhibitors in a Danish real life non-small cell lung cancer population: a retrospective cohort study

Mouritzen M, Larus A, Ladekarl M, Meldgaard P, Nielsen A, Livbjerg A, Larsen J, Halla Skuladottir H, Kristiansen C, Wedervang K, Tine Schytte T, Hansen K, Østby AC, Frank M, Lauritsen J, Sørensen J, Langer S, Persson G, Andersen J, Frary J, Drivsholm L, Vesteghem C, Christensen H, Bjørnhart B, Pøhl M. Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC-Real World Efficacy