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

NCT04115410 | Unknown FDA Drug

• 1 other identifier: SKKU-2019-PD1ICI
• Study Type: observational
• Target: 4,724
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (1)

• Hazard ratio for immune-related adverse events

  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 Outcomes (1)

• Hazard ratio for eleven subdivided groups of immune-related adverse events by organ class

  August 2017 to December 2018

Study Arms (2)

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

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

Interventions

PD-1 inhibitor 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.

Also known as: OPDIVO, KEYTRUDA, TECENTRIQ

PD-1 inhibitor

Chemotherapy Drugs, Cancer 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).

Also known as: Carboplatin, Cisplatin, Vinorelbine, Gemcitabine, Pemetrexed, Docetaxel, Vinblastine, Mitomycin C, Gefitinib, Erlotinib, Afatinib, Crizotinib, Ceritinib, Alectinib, Osimertinib

Chemotherapy Drugs, Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sungkyunkwan University: lead
• Ministry of Food and Drug Safety, Korea: collaborator

Related Publications (9)

• Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhaufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crino L, Blumenschein GR Jr, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F, Brahmer JR. Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Oct 22;373(17):1627-39. doi: 10.1056/NEJMoa1507643. Epub 2015 Sep 27.

  PMID: 26412456 BACKGROUND

• Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

  PMID: 26028407 BACKGROUND

• Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.

  PMID: 27718847 BACKGROUND

• Postow MA, Sidlow R, Hellmann MD. Immune-Related Adverse Events Associated with Immune Checkpoint Blockade. N Engl J Med. 2018 Jan 11;378(2):158-168. doi: 10.1056/NEJMra1703481. No abstract available.

  PMID: 29320654 BACKGROUND

• Baxi S, Yang A, Gennarelli RL, Khan N, Wang Z, Boyce L, Korenstein D. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018 Mar 14;360:k793. doi: 10.1136/bmj.k793.

  PMID: 29540345 BACKGROUND

• Johnson DB, Sullivan RJ, Menzies AM. Immune checkpoint inhibitors in challenging populations. Cancer. 2017 Jun 1;123(11):1904-1911. doi: 10.1002/cncr.30642. Epub 2017 Feb 27.

  PMID: 28241095 BACKGROUND

• Kobayashi K, Nakachi I, Naoki K, Satomi R, Nakamura M, Inoue T, Tateno H, Sakamaki F, Sayama K, Terashima T, Koh H, Abe T, Nishino M, Arai D, Yasuda H, Kawada I, Soejima K, Betsuyaku T; Keio Lung Oncology Group (KLOG). Real-world Efficacy and Safety of Nivolumab for Advanced Non-Small-cell Lung Cancer: A Retrospective Multicenter Analysis. Clin Lung Cancer. 2018 May;19(3):e349-e358. doi: 10.1016/j.cllc.2018.01.001. Epub 2018 Jan 5.

  PMID: 29398578 BACKGROUND

• Naidoo J, Wang X, Woo KM, Iyriboz T, Halpenny D, Cunningham J, Chaft JE, Segal NH, Callahan MK, Lesokhin AM, Rosenberg J, Voss MH, Rudin CM, Rizvi H, Hou X, Rodriguez K, Albano M, Gordon RA, Leduc C, Rekhtman N, Harris B, Menzies AM, Guminski AD, Carlino MS, Kong BY, Wolchok JD, Postow MA, Long GV, Hellmann MD. Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy. J Clin Oncol. 2017 Mar;35(7):709-717. doi: 10.1200/JCO.2016.68.2005. Epub 2016 Sep 30.

  PMID: 27646942 BACKGROUND

• Remon J, Mezquita L, Corral J, Vilarino N, Reguart N. Immune-related adverse events with immune checkpoint inhibitors in thoracic malignancies: focusing on non-small cell lung cancer patients. J Thorac Dis. 2018 May;10(Suppl 13):S1516-S1533. doi: 10.21037/jtd.2017.12.52.

  PMID: 29951303 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Immune Checkpoint Inhibitors; Nivolumab; pembrolizumab; atezolizumab; Antineoplastic Agents; Carboplatin; Cisplatin; Vinorelbine; Gemcitabine; Pemetrexed; Docetaxel; Vinblastine; Mitomycin; Gefitinib; Erlotinib Hydrochloride; Afatinib; Crizotinib; ceritinib; alectinib; osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Therapeutic Uses; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Mitomycins; Indolequinones; Quinones; Azirines; Quinazolines; Amides; Piperidines; Aminopyridines; Pyridines

Study Officials

• Ju-Young Shin, PhD

  Sungkyunkwan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yeon-Hee Baek

CONTACT

+82-31-299-4377; waterlily9@skku.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 4, 2019
• Study Start: July 1, 2020
• Primary Completion: September 23, 2021
• Study Completion: December 31, 2021
• Last Updated: May 28, 2020

Record last verified: 2020-05