Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors

Sponsor

Johns Hopkins University (Other)

Overall Status

Completed

CT.gov ID

NCT04898751

Collaborator

(none)

2,214

Enrollment

Location

152

Actual Duration (Months)

14.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Immune checkpoint inhibitors (ICIs) are associated with a wide variety of cutaneous immune-related adverse events (cirAEs). These cirAEs are reported to be the most common immune-related adverse events (irAEs) and the first to appear. This study examines the appearance of cirAEs within the World Health Organization (WHO) pharmacovigilance database, VigiBase.

Condition or Disease	Intervention/Treatment	Phase
Cutaneous Toxicity From ICI Therapy	Drug: Immune checkpoint inhibitor (ICI)

Detailed Description

ICIs have revolutionized clinical oncologic care. The ICIs that are currently FDA approved fall into three main categories: those that block the cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4; ipilimumab), block the programmed cell death protein-1 (anti-PD-1; nivolumab, pembrolizumab, cemiplimab), and block the programmed cell death ligand-1 (anti-PD-L1; atezolizumab, avelumab, durvalumab) pathway. There is a considerable diversity of cirAEs that have been reported with these ICIs in both monotherapy and combination therapy.

VigiBase is the WHO pharmacovigilance database that monitors individual case safety reports associated with certain drugs. The largest database of its kind in the world, VigiBase is managed by the Uppsala Monitoring Center (UMC) in Sweden, and since its inception in 1967 has received over 19 million individual case safety reports (ICSRs) from over 130 contributing countries. In this study, the investigators examine the appearance of cutaneous immune related adverse events in the setting of immunotherapy within VigiBase.

Study Design

Study Type:

Observational [Patient Registry]

Actual Enrollment :

2214 participants

Observational Model:

Other

Time Perspective:

Cross-Sectional

Official Title:

Analysis of Reporting of Cutaneous Toxicities Associated With Immune Checkpoint Inhibitors

Actual Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Aug 31, 2020

Actual Study Completion Date :

Aug 31, 2020

Arms and Interventions

Arm	Intervention/Treatment
Cutaneous toxicity Patients who reported a cutaneous immune related adverse event following ICI initiation with appropriate chronology that indicates drug toxicity.	Drug: Immune checkpoint inhibitor (ICI) Immune checkpoint inhibitors included were targeting either PD-1, PD-L1 or CTLA-4, and had received FDA approval at the time of study (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33). Other Names: Ipilimumab (Yervoy, L01XC11) Nivolumab (Opdivo, L01XC17) Pembrolizumab (Keytruda, L01XC18) Durvalumab (Imfinzi, L01XC28) Avelumab (Bavencio, L01XC31) Atezolizumab (Tecentriq, L01XC32) Cemiplimab (Libtayo, L01XC33)

Arm

Intervention/Treatment

Cutaneous toxicity

Patients who reported a cutaneous immune related adverse event following ICI initiation with appropriate chronology that indicates drug toxicity.

Drug: Immune checkpoint inhibitor (ICI)

Immune checkpoint inhibitors included were targeting either PD-1, PD-L1 or CTLA-4, and had received FDA approval at the time of study (ATC classification): Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).

Other Names:

Ipilimumab (Yervoy, L01XC11)

Nivolumab (Opdivo, L01XC17)

Pembrolizumab (Keytruda, L01XC18)

Durvalumab (Imfinzi, L01XC28)

Avelumab (Bavencio, L01XC31)

Atezolizumab (Tecentriq, L01XC32)

Cemiplimab (Libtayo, L01XC33)

Outcome Measures

Primary Outcome Measures

Cutaneous toxicity of ICIs [From 01/01/2008 to 08/31/2020]
Number of reported adverse events associated with ICIs within the Systems Organ Class (SOC) "Skin and subcutaneous disorders" with one of the 7 FDA-approved ICIs Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), or Cemiplimab (L01XC33), alone or in any combination with each other.

Secondary Outcome Measures

Reporting odds ratio for monotherapy vs combination therapy [From 01/01/2008 to 08/31/2020]
Reporting odds ratio for appearance of cirAEs, comparing the odds of appearance of cirAEs with monotherapy with PD-1, PD-L1, or CTLA-4 against combination therapy with a PD-1/PD-L1 and CTLA-4 agent.
Reporting odds ratio for differing monotherapy [From 01/01/2008 to 08/31/2020]
Reporting odds ratio for appearance of cirAEs comparing monotherapy with PD1 or PD-L1 against monotherapy with CTLA-4
Co-occuring irAEs [From 01/01/2008 to 08/31/2020]
Prevalence (%) of co-occuring irAEs within other organ systems (GI, endocrine/metabolic, pulmonary, cardiac, renal, hematologic, neurologic, rheumatologic, and ophthalmologic) with cirAEs.
Disproportionality assessment of cirAEs with ICIs [From 01/01/2008 to 08/31/2020]
Information component (IC), a Bayesian confidence neural network propagation method devised by the Uppsala Monitoring Center, will determine significant disproportionate signal of cirAEs associated with ICIs if >0 at the bottom of the 95% confidence interval (IC025 > 0).
Indication [From 01/01/2008 to 08/31/2020]
Prevalence (%) of malignancy types (such as melanoma, pulmonary, and renal cell carcinoma) for patients receiving ICIs and developing cirAEs.
Time to onset [From 01/01/2008 to 08/31/2020]
Time to onset of cirAEs after ICI administration, measured in days.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Treated with either Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32), and Cemiplimab (L01XC33).
Developed an adverse reaction that was submitted to a pharmacovigilance center and was determined to be related to aforementioned immune checkpoint inhibitors.
Adverse reaction was determined to be within the System Organ Class (SOC) "Skin and subcutaneous disorder".

Exclusion Criteria:

Adverse event was determined not to be immune-related (for example, infectious etiology) or was a symptom (e.g., edema).
Adverse event developed before the administration of ICI.