Incidence, Clinical Management and Molecular Factors Associated With the Development of Immune-related Adverse Events in Cancer Patients Receiving PD-1 and PD-L1 Inhibitors: a Prospective Observational Study
Trial Snapshot
- Phase
- Not Applicable
- Sponsor
- Enrollment
- 200
- Locations
- 1
- Primary Endpoint
- Incidence of irAEs
Study Overview
Brief Summary
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti- PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines. Durable responses and prolongation of survival with these agents come at the price of the development of immune related adverse events (irAEs). Innovative tools are required in order to manage irAEs and to prevent their potential relapse, with the goal to improve the outcome of patients. In this regard, the Investigators aim to develop a multidisciplinary clinical pathway for cancer patients that are treated with immune checkpoint inhibitors.
Detailed Description
Recent evidences in immuno-oncology showed an important role of the immune system in tumor control. In fact, immune response, both innate and adaptive one, is the first defensive mechanism against cancer. However, several tumors, during their progression, develop an immune-tolerance characterized by the activation of immune inhibitory pathways including PD-1 and PD-L1.
The recent introduction of anti-PD-1 (nivolumab and pembrolizumab) and anti-PD-L1 (atezolizumab, durvalumab, avelumab) immune checkpoint inhibitors revolutionized oncological guidelines.
Currently, the aforementioned agents are approved for the treatment of advanced malignant melanoma; non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC) and the number of treatment indications for immune checkpoint inhibitors is expanding. Durable responses and prolongation of survival with these agents come at the price of the development of immune-related adverse events (irAEs).
Immune-related adverse events are due to the loss of immune-tolerance towards structures of the self, with the induction of chronic inflammation with an autoimmune mechanism that can involve numerous organs and systems. The most frequent irAEs reported in clinical trials are represented by skin toxicity, gastrointestinal toxicity, endocrine toxicity, pulmonary toxicity, and others such as polymyalgia rheumatica, polyarthritis, myositis, nephritis, polyradiculoneuritis, encephalitis and myocarditis.
The irAEs reported in clinical trials with nivolumab amount to a maximum of 85% considering all grade of toxicities, while approximately 75% of patients treated with pembrolizumab presented irAEs. Grade 3/4 irAEs were reported in 10% of patients treated with anti-PD-1. With atezolizumab fewer patients had treatment-related grade 3 or 4 adverse events (15%).
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients above 18 years of age;
- •Cyto-histological diagnosis of one of the following cancers:
- •advanced melanoma;
- •metastatic or locally advanced non-small cell lung cancer;
- •advanced renal cell carcinoma;
- •metastatic or locally advanced urotelial carcinoma;
- •squamous cell carcinoma of the head and neck;
- •Hodgkin lymphoma;
- •Merkel-cell carcinoma;
- •New prescription of one of the following PD-1/PD-L1 inhibitors:
- •pembrolizumab
- •atezolizumab
- •durvalumab alone or in combination therapy, following the indications of the Italian regulatory agency (AIFA).
Exclusion Criteria
- •Patients that refuse and/or are not able to sign the Informed Consent;
- •Parents/guardians or subjects who, in the opinion of the Investigator, may be noncompliant with study schedules or procedures;
- •No contraindications to the treatment with PD-1/PD-L1 antibodies, following the indications of the Italian regulatory agency (AIFA).
- •Subjects that do not meet all of the enrollment criteria may not be enrolled.
Outcomes
Primary Outcomes
Incidence of irAEs
Time Frame: 24 months
To determine the incidence and the characteristics of irAEs in a real-world setting
Risk factors for irAEs
Time Frame: 24 months
To determine the risk factors for the development of irAEs
Impact of irAEs
Time Frame: 24 months
To determine the impact of irAEs on patients' prognosis
Therapies of irAEs
Time Frame: 24 months
To determine the effect of immunosuppressive therapies on tumor progression and patient's prognosis
Secondary Outcomes
- Clinical care pathway(24 months)
- Quality of life(24 months)
- Biomarkers(24 months)
- Exploratory analyses(24 months)
Investigators
Armando Gabrielli
Full Professor
Università Politecnica delle Marche