Neuroendocrine tumours (NETs) are cancers that begin in specialised cells called neuroendocrine cells. Neuroendocrine cells are similar to other hormone producing cells that release hormones into the bloodstream. NETs are rare and can occur anywhere in the body.
Lutathera (lutetium Lu 177 dotatate) has been licenced for use in the United States (US) and the European Union (EU). However, little is known, from a real-world evidence standpoint, on the resource utilisation, survival rates and clinical characteristics of patients treated with the drug. This study will address these evidence gaps in the literature.
Our aim is to analyse resource utilisation from diagnosis until a patient’s last observation in the database across subsequent stages/grades of disease and lines of treatment for patients with NETs, treated with Lutathera. The intention is to map the treatment pathway of NETs patients using data from CPRD Gold and Aurum linked to HES and NRAS databases in order to gain greater insights into the extent of resource utilisation and treatment intensity for this cohort. In addition, we wish to compare overall survival (OS) i.e. the length of time between a patient's initial treatment for a disease and death; and progression free survival (PFS) i.e. the length of time a patient lives with a disease without the disease becoming worse - among patients treated with Lutathera vs patients not treated with Lutathera. From a public health point of view, this research will provide insights that will help to optimise treatment patterns in clinical practice for patient with NETs.
B. Technical Summary (Max. 300 words)
Neuroendocrine tumours (NETs) are a form of rare tumour that can develop in many organs of the body. They secrete various bio amines and peptides from endocrine cells in the endocrine and central nervous systems, including in the gastrointestinal tract, the pancreas and the lungs.
The primary objective of this study is to analyse resource utilisation from diagnosis until a patient’s last observation in the database. Patients with NETs will be identified using ICD9, ICD10, OPCS procedure and ICD-O-3 diagnosis codes. Treatment with Lutathera will be identified using the OPCS procedure code X657 in the RTDS database. As such we will require linked data to the following variables - (primaryprocedureopcs) and (proceduredate) from the data.
There are multiple secondary objectives which are listed below:
1. Compare overall survival of patients with NETs, treated with Lutathera vs other treatments
2. Compare overall survival by treatment frequency among Lutathera patients. Patients will be subdivided into the following groups depending on the frequency with which they receive treatment
3. Compare HCRU by treatment frequency among Lutathera patients. Patients will be subdivided into the following groups depending on the frequency with which they receive treatment
4. Describe the patient and clinical characteristics of both cohorts
5. Describe healthcare resource use and costs among patients re-treated with Lutathera by disease stage and line of therapy
6. Compare overall survival of patients with NETs re-treated with Lutathera vs other treatments
7. Compare PFS of patients with NETs treated with Lutathera vs other treatments
Descriptive statistics will be produced on patient characteristics at baseline (pre index) and resource utilisation and treatment pathways in the post index period. Predictors of survival will be identified using Cox proportional hazard models.
C. Outcomes to be Measured
The primary endpoint is resource use (all cause) by stage of disease (if possible) and line of therapy in the follow-up period. Note that, surgery or radiotherapy shortly after first diagnosis should not be considered as a LoT.
Healthcare resource use will be presented pre- and post-index date for the following outcomes and reported as NETs specific and all-cause utilisation. Resource use will be defined in terms of the following:
• Number of General Practitioner (GP); specialist (based on HES) visits; and specialist referrals
• Number of Accident & Emergency (A&E) admissions (based on a diagnosis acquired during the stay)
• Number of hospitalizations and the length of stay
• Entry to palliative care
• Prescription drugs associated with NETs patients
In addition, healthcare costs will be estimated for each patient in each of the settings mentioned above. Patients will be defined as having entered palliative care using the disdest (destination on discharge) variable in the HES APC dataset where a patient returns of value=88 – “Non-NHS (other than local Authority) run hospice or similar
Both the primary and secondary objectives will be examined in two groups (those patients treated with Lutathera (known as the treatment group) and those not treated with Lutathera (the control group). Both cohorts will have had a diagnosis of NETs in the 6 months prior to their index treatment (see Figure 1 below).
1. The endpoint of interest in estimating overall survival will be time to treatment failure – and will be defined as the time from index treatment to death, or 31 December 2020 whichever is earlier. ONS mortality data will be linked to CPRD and HES data to establish a date of death if applicable. If date of death is not available, death certificate data will determine if a patient has died (dco). Patients without an event (death) will be censored on the last date of activity in the data. Patients without an event (death) will be censored on the last date of activity in the data
2. The endpoint of interest is time to treatment failure and is defined as the time from index treatment to death or 31 December 2021, whichever comes first. As in (1) above, ONS mortality data will be linked to CPRD and HES data to access date of death information in particular for use in estimating overall survival.
3. HCRU will be calculated in terms of the following:
• Number of General Practitioner (GP), specialist (based on HES) visits, and specialist referrals
• Number of Accident & Emergency (A&E) admissions (based on a diagnosis acquired during the stay)
• Number of hospitalizations and the length of stay
• Entry to palliative care
Similar to the primary objective, healthcare costs will be estimated for each patient in each of the settings mentioned above.
4. Number and percentage (%) of patients with respect to their demographic and clinical characteristics among both cohorts
• Geographical regions where patients are from?
• Location where patients are treated i.e. the name of the treatment centre where a Lutathera patients are treated
• Number of months between index diagnosis and index treatment
• Number and percentage (%) of patients with secondary malignancies in both cohorts
5. Resource use among re-treated patients will be defined in terms of the following:
• Number of General Practitioner (GP), specialist (based on HES) visits, and specialist referrals
• Number of Accident & Emergency (A&E) admissions (based on a diagnosis acquired during the stay)
• Number of hospitalizations and the length of stay
• Entry to palliative care
• Prescription drugs associated with NETs patients
6. The endpoint of interest is time to treatment failure and is defined as the time from index treatment to death or 31 December 2021, whichever comes first. As in (1) above, ONS mortality data will be linked to CPRD and HES data to access date of death information in particular for use in estimating overall survival.
7. The endpoint of interest is time to treatment failure and is defined as the time from index treatment to progression of disease. PFS will be estimated by making use of information in SACT and proxies for progression such as therapy switch not for reasons of side effects to the next treatment, increase of dose (actual_dose_per_administration)and movement to palliative care.
Patrick Ward - Chief Investigator - Novartis Ireland Limited
Patrick Ward - Corresponding Applicant - Novartis Ireland Limited
Nicholas REED - Collaborator - Gartnavel Hospital
Oscar Leeuwenkamp - Collaborator - NOVARTIS
Priyanka . - Collaborator - Novartis Healthcare (India) Pvt. Ltd.
Usha Naik - Collaborator - NOVARTIS
LINTU M K - Collaborator - Novartis Healthcare (India) Pvt. Ltd.
Neeraj Tiwari - Collaborator - Novartis Healthcare (India) Pvt. Ltd.
HES Accident and Emergency;HES Admitted Patient Care;HES Diagnostic Imaging Dataset;HES Outpatient;NCRAS Cancer Registration Data;NCRAS National Radiotherapy Dataset (RTDS) data;NCRAS Systemic Anti-Cancer Treatment (SACT) data;ONS Death Registration Data;Practice Level Index of Multiple Deprivation