ICI Discontinuation Appropriate after Grade ≥2 Immune-Related AEs in Patients with Stage IV NSCLC

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Lung cancer remains the leading cause of cancer-related death worldwide, accounting for approximately 1.8 million deaths in 2020. In the United States, it is estimated that >236,000 new cases of lung cancer were diagnosed in 2022. For patients with stage IV non–small-cell lung cancer (NSCLC), the 5-year survival rate remains poor. Immune checkpoint inhibitors (ICIs) have become commonly used as a first-line or early-line treatment for patients with advanced NSCLC and have been found to improve survival and durable responses when used in this patient group. Although generally better tolerated than chemotherapy, ICIs are associated with immune-related adverse events (irAEs), which cause inflammatory autoimmune tissue damage to organ systems. These irAEs occur in various severities and frequencies. It has been found that better responses and clinical outcomes are associated with irAEs, and patients with grade 1 irAEs can usually continue their ICI treatment. Patients who have grade ≥2 irAEs, however, will require their treatment to be discontinued, and immunosuppressant therapy will need to be initiated to avoid deleterious effects. After discontinuation and immunosuppressant treatment, if there is improvement to grade ≤1 irAE, ICI treatment can be resumed. However, the chance of recurrence or the efficacy of further treatment is uncertain.

To understand the safety and efficacy of rechallenge or discontinuation of ICIs in patients with stage IV NSCLC who experienced grade ≥2 irAEs, a single-center retrospective study of 1051 patients with stage IV NSCLC was conducted. The investigators found that treatment interruption was necessary in 99 of these patients due to grade ≥2 irAEs. Treatment was discontinued in 59 patients. Rechallenge with ICI therapy was conducted in 40 patients. In the rechallenge group, the initial irAEs experienced by patients were less severe, and 24 had a recurrence of the same de novo irAEs. Second occurrence of grade ≥2 irAEs were experienced by 20 patients in the rechallenge group. No patients experienced grade 4 irAEs or death related to irAEs after rechallenging. No statistically significant difference in progression-free survival or overall survival between the patient group who discontinued treatment and the rechallenge group was found. Permanently discontinuing ICIs is an appropriate response after grade ≥2 irAEs for patients with stage IV NSCLC.

Source: Guo M, VanderWalde AM, Yu X, Vidal GA, Tian GG. Immune checkpoint inhibitor rechallenge safety and efficacy in stage IV non-small cell lung cancer patients after immune-related adverse events. Clin Lung Cancer. 2022;23(8):686-693.

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