Clinical trial NCT04115410: PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study
Official title: PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Carcinoma, Non-Small-Cell Lung
Immune-Related Adverse Events
Keywords: PD-1 inhibitor
Nivolumab
Pembrolizumab
Atezolizumab
Immune-Related Adverse Events
Carcinoma, Non-Small-Cell Lung
Lead sponsor: Sungkyunkwan University
Sponsor class: OTHER
Collaborators: name: Ministry of Food and Drug Safety, Korea
First posted: 2019-10-04
Enrollment: 4724
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be formed by identifying all patients newly treated with standard chemotherapy who subsequently switched to PD-1 inhibitors, from 21 August 2017 to 31 September 2018, with follow-up until 31 December 2018. Patients who remained on standard chemotherapy treatment will be selected as comparators.

Brief summary: The objective of our study is to assess the risk of immune-related adverse events associated with PD-1 inhibitors use compared to standard chemotherapy use in patients with non small cell lung cancer, using nationwide healthcare database.

Detailed description: This observational, retrospective cohort study will evaluate the risk of immune-related adverse events associated with PD-1 inhibitors use compared to standard chemotherapy use in patients with non small cell lung cancer, using nationwide healthcare database. PD-1 inhibitors will be defined as nivolumab, pembrolizumab, and atezolizumab. Standard chemotherapy will be defined as cytotoxic chemotherapy or tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors). The investigators will assess exposure on the cohort entry using the intention-to-treat approach with the 6-month exposure risk window from the first PD-1 inhibitor prescription to avoid bias from informative censoring. Immune-related adverse events will be defined by using pre-specified algorithms using diagnosis and corticosteroid prescription records (high dose of oral corticosteroids, defined as ≥ 30 mg/day, or systemic corticosteroid injection) to reduce outcome misclassification. The investigators will use a multivariable Cox proportional hazard model to estimate hazard ratio (HR) and 95% confidence intervals (CI). The model will be adjusted for pre-existing autoimmunity, history of lung cancer surgery, radiation therapy, tyrosine kinase inhibitor use, and previous systemic corticosteroid use. All analyses will be undertaken using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).

Eligibility criteria: Inclusion Criteria:

* Individuals who were diagnosed with lung cancer (ICD-10: C33-C34) between 2017 and 2018.

Exclusion Criteria:

* Individuals less than 18 years of age
* Individuals received any systemic anticancer therapies in 2007
* Having no records of prescription of PD-1 inhibitors or standard chemotherapy at least once between 2017 and 2018
* Individuals received treatments indicated for small cell lung cancer (etoposide, ifosfamide, irinotecan, belotecan, and topotecan) on or before the first date of standard chemotherapy to restrict study subjects to patients with non small cell lung cancer only.

Primary outcomes:
measure: Hazard ratio for immune-related adverse events
timeFrame: August 2017 to December 2018
Secondary outcomes:
measure: Hazard ratio for eleven subdivided groups of immune-related adverse events by organ class
timeFrame: August 2017 to December 2018
Other outcomes:
Locations:
Study officials:
affiliation: Sungkyunkwan University
name: Ju-Young Shin, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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