PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study

NCT ID: NCT04115410

Last Updated: 2020-05-28

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 4724 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-07-01
• Study Completion Date: 2021-12-31

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).

Conditions

Carcinoma, Non-Small-Cell Lung; Immune-Related Adverse Events

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

PD-1 inhibitor

Patients over 18 years of age with a diagnosis of non-small cell lung cancer and being received PD-1 inhibitors as a second line treatment from cytotoxic chemotherapy or as a third line for those received tyrosine kinase inhibitors as a first line, from August 2017 (the first month PD-1 inhibitors were reimbursed in South Korea) to September 2018.

PD-1 inhibitor

Intervention Type: DRUG

PD-1 inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer. PD-1 and PD-L1 are both proteins present on the surface of cells. Immune checkpoint inhibitors such as these are emerging as a front-line treatment for several types of cancer. The investigators will include nivolumab, pembrolizumab, and atezolizumab as PD-1 inhibitors as these drugs are reimbursed by health authority of South Korea.

Chemotherapy Drugs, Cancer

Patients over 18 years of age with a diagnosis of non-small cell lung cancer and being received cytotoxic chemotherapy or tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) from August 2017 to September 2018. Each patient switching to PD-1 inhibitor will be matched to three reference standard chemotherapy users.

Chemotherapy Drugs, Cancer

Intervention Type: DRUG

Chemotherapy is a type of pharmacotherapy for cancer, that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. The investigators will include cytotoxic chemotherapy and tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors).

Interventions

PD-1 inhibitor

PD-1 inhibitors are a group of checkpoint inhibitors being developed for the treatment of cancer. PD-1 and PD-L1 are both proteins present on the surface of cells. Immune checkpoint inhibitors such as these are emerging as a front-line treatment for several types of cancer. The investigators will include nivolumab, pembrolizumab, and atezolizumab as PD-1 inhibitors as these drugs are reimbursed by health authority of South Korea.

Intervention Type: DRUG

Chemotherapy Drugs, Cancer

Chemotherapy is a type of pharmacotherapy for cancer, that uses one or more anti-cancer drugs as part of a standardized chemotherapy regimen. The investigators will include cytotoxic chemotherapy and tyrosine kinase inhibitors (epidermal growth cell receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors).

Intervention Type: DRUG

Other Intervention Names

OPDIVO; KEYTRUDA; TECENTRIQ; Carboplatin; Cisplatin; Vinorelbine; Gemcitabine; Pemetrexed; Docetaxel; Vinblastine; Mitomycin C; Gefitinib; Erlotinib; Afatinib; Crizotinib; Ceritinib; Alectinib; Osimertinib

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Food and Drug Safety, Korea

OTHER_GOV

Sponsor Role: collaborator

Sungkyunkwan University

OTHER

Sponsor Role: lead

Responsible Party

Ju-Young Shin

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ju-Young Shin, PhD

Role: PRINCIPAL_INVESTIGATOR

Sungkyunkwan University

Central Contacts

Yeon-Hee Baek

Role: CONTACT

waterlily9@skku.edu

+82-31-299-4377

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Other Identifiers

SKKU-2019-PD1ICI

Identifier Type: -

Identifier Source: org_study_id