Observational study - nivolumab in 2nd line oesophageal cancer EAMS
Research type
Research Study
Full title
Clinical Characteristics, Outcomes and quality of Life in Patients with Squamous Cell Oesophageal Carcinoma Receiving Nivolumab After Prior Chemotherapy as Part of an Early Access to Medicines Scheme (EAMS) Program in the United Kingdom
IRAS ID
272203
Contact name
John Bridgewater
Contact email
Sponsor organisation
Bristol-Myers Squibb Pharmaceuticals Ltd
Duration of Study in the UK
1 years, 2 months, 30 days
Research summary
Summary of Research
The purpose of this observational study is to characterise patients with squamous cell oesophageal cancer who receive nivolumab treatment as part of an Early Access to Medicines Scheme (EAMS) program.This observational study consists of collecting and analysing data from medical records and patient questionnaires for patients enrolled in the EAMS program. The study includes two aspects:
1. Patients will be asked to complete a short questionnaire on health-related quality of life, called the EuroQuol Quality of Life 5Dimensions 3-Levels (EQ-5D-3L). The EQ-5D-3L will be completed at enrolment (the date consent form is signed) then every 2 weeks over a 24-week period after enrolment.
2. Physicians will review patient medical records to provide details of the patient status and stage of disease, at the time the patient has completed their treatment with nivolumab, and at 6 and 12 months post treatment completion.Patients will be given the option to consent to one or both aspects of the study described above.
Data collected in this study may be used for further assessment of nivolumab by the National Institute of Health and Care Excellence (NICE) and the Scottish Medicines Consortium (SMC) to assist them in the decision making when considering whether nivolumab should be recommended for the treatment of patients as part of standard NHS care.
It is not possible to provide an estimate of the number of patients who will participate in this study as this will depend on the number of patients enrolled into the EAMS from UK hospitals.
Data analyses will be descriptive in nature. Patient data will be stored securely without any patient identifiable information so patient privacy is protected. Study results will be summarised and included in scientific presentations and publications.
Summary of Results
Of the 87 patients who enrolled in the oesophageal cancer Early Access to Medicines Scheme (EAMS) program and had received at least one treatment of nivolumab, 44 patients (55.7%) from 35 study sites in the UK participated in the observational research study. Most study sites (80%, n=28) were located in England and other sites were located in Scotland (14.3%, n=5), Wales (2.9%, n=1) and Northern Ireland (2.9%, n=1). Among the 28 sites in England, seven sites (20.0%) were based in the North, 10 sites (28.6%) were based in the South, South Central or Midlands, and 11 sites (31.4%) were based in London, East or Southeast England.The observational research comprised two components: medical chart review and completion of EQ-5D-3L (EQ-5D), which described a patient’s general health in five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression).
Of the 44 patients who consented to at least one component of the observational research, 32 patients consented to both medical chart review and completion of EQ-5D and 12 patients consented to only medical chart review. Seventeen of the 32 patients who consented to medical chart review and completion of EQ-5D completed at least one EQ-5D.All patients (n=44) had squamous cell carcinoma (SCC). The median age at the time of EAMS enrolment (baseline) was 66.5 years (range: 29 to 84), nearly two-thirds of the patients were male (65.9%, n=29) and most were white (88.6%, n=39).
Twenty-seven patients (61.4%) (n=27) had at least one pre-existing illness or disease, including 25.0% (n=11) with three or more pre-existing illnesses or diseases, and 93.2% (n=41) of patients were taking one or more medication. The most reported pre-existing illnesses or diseases were high blood pressure (40.7%, n=11) and type 2 diabetes (14.8%, n=4).The ECOG, which ranges from 0-5, describes a patient’s level of functioning in terms of their ability to care for themselves, daily activity, and physical ability; an ECOG score of 0 indicates that a patient is fully active and able to carry on all pre-disease performance without restriction. In this study, most patients (90.9%, n=40) had an ECOG score of 0 or 1. Most (70.5%, n=31) patients had not received surgery for SCC, had not had a tube placed in the oesophagus or respiratory tract known as stent therapy (68.2%, n=30), or had stopped responding to or became intolerant to prior treatment (68.2%, n=30). All patients had received at least one prior systemic treatment before they started taking nivolumab; Cisplatin with Capecitabine (34.1%, n=15) and Capecitabine with Oxaliplatin (20.5%, n=9) were the most reported prior systemic treatments. Cancer had spread to two or more organs in nearly half (45.5%, n=9) of patients; the lymph nodes (65.9%, n=29) and lung (43.2%, n=19) were the most reported sites of metastases.
The demographic characteristics, disease characteristics, and medical history at baseline were similar in patients who only consented to the medical chart review component of this study (n=12) compared to the 17 patients who consented to medical chart review and EQ-5D and completed at least one EQ-5D, except the patients who consented to medical chart review only tended to be males (83.3% vs 58.8%), had pre-existing illnesses or diseases (75.0% vs 52.9%), had prior surgery for oesophageal cancer (58.3% vs 17.6%), had stent therapy in the oesophagus or respiratory tract (58.3% vs 23.5%), and had an ECOG performance status of 0 (33.3% vs 17.6%).
Among patients (n=44) who consented into the observational research, the median nivolumab treatment duration was 2.6 months (95% CI: 2.0-3.0). After the start of nivolumab treatment, 34% (95% CI: 21.2-48.9) of patients remained on treatment after 3 months, 14.0% (95% CI: 5.7-25.9) remained on treatment after 6 months, and no patient was on treatment after 12 months. Median progression-free survival, which was the length of time, during and after the treatment of oesophageal cancer, that a patient lived with the disease but the disease did not get worse was 3.8 months (95% CI: 2.6-4.9) in this study population. The median overall survival, which was the length of time that patients who were diagnosed with the disease remained alive, was 5.5 months (95% CI: 3.9-not estimable).
For patients who consented to both the medical chart review and EQ-5D and completed at least one questionnaire (N=17), a total of 9 patients (52.9%) completed all five domains at baseline. The EQ-Visual Analog Score (EQ-VAS) score (0-100), which records the patient’s own judgement on their health; a score of 100 means the best health the patient can imagine. In this study, the mean EQ-VAS score was 63.4 (SD: 18.3) and mean health utility scores was 0.6 (SD: 0.2), which combined a patient’s response across five domains into one score. Of the 7 out of the 9 patients who completed both medical chart review and EQ-5D and returned the questionnaire before the start of nivolumab treatment and at the time nivolumab treatment was stopped, most patients had no changes since before nivolumab treatment for each of the five EQ-5D-3L domain scores (self-care, usual activities, pain/discomfort, and anxiety/depression) at the end of nivolumab treatment.
In the overall study population (n=44), 28 (63.6%) patients reported at least one adverse event (AE), and 3 (6.8%) patients reported at least one AE related to nivolumab treatment. Overall, 73 AEs were reported, including 66 (90.4%) assessed as being unrelated to nivolumab treatment and 7 (9.6%) related to nivolumab treatment. Of the 73 reported AEs, 68 (93.2%) AEs were classified as serious, including 2 (2.7%) SAEs related to nivolumab. The most frequently reported AEs were malignant neoplasm progression (35.6%, n=26), pneumonia (6.8%, n=5), and pulmonary sepsis (2.7%, n=2).
REC name
London - Central Research Ethics Committee
REC reference
20/LO/0736
Date of REC Opinion
26 May 2020
REC opinion
Further Information Favourable Opinion