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

May 27, 2020 updated by: Ju-Young Shin, Sungkyunkwan University
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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).

Study Type

Observational

Enrollment (Anticipated)

4724

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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.

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Drug: 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.
Other Names:
  • KEYTRUDA
  • TECENTRIQ
  • OPDIVO
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.
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).
Other Names:
  • Gemcitabine
  • Cisplatin
  • Carboplatin
  • Gefitinib
  • Docetaxel
  • Vinblastine
  • Vinorelbine
  • Mitomycin C
  • Pemetrexed
  • Afatinib
  • Erlotinib
  • Osimertinib
  • Alectinib
  • Ceritinib
  • Crizotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hazard ratio for immune-related adverse events
Time Frame: August 2017 to December 2018
The ratio of hazard rates of immune-related adverse events in PD-1 inhibitor users vs. standard chemotherapy users
August 2017 to December 2018

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Hazard ratio for eleven subdivided groups of immune-related adverse events by organ class
Time Frame: August 2017 to December 2018
The ratio of hazard rates of eleven subdivided organ-specific immune-related adverse events (pulmonary, endocrine, cardiovascular, gastrointestinal, hepatic, muscluoskeletal, neurological, ocular, renal, skin, and hematologic) in PD-1 inhibitor users vs. standard chemotherapy users
August 2017 to December 2018

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sungkyunkwan University

Collaborators

Ministry of Food and Drug Safety, Korea

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

July 1, 2020

Primary Completion (ANTICIPATED)

September 23, 2021

Study Completion (ANTICIPATED)

December 31, 2021

Study Registration Dates

First Submitted

October 2, 2019

First Submitted That Met QC Criteria

October 2, 2019

First Posted (ACTUAL)

October 4, 2019

Study Record Updates

Last Update Posted (ACTUAL)

May 28, 2020

Last Update Submitted That Met QC Criteria

May 27, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SKKU-2019-PD1ICI

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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