Immune Checkpoint Inhibitor Use in Non–Small-Cell Lung Cancer Causes Primarily Mild Adverse Events

Lung cancer is the leading cause of cancer-related death, with non–small-cell lung cancer (NSCLC) comprising 85% of all lung cancer cases. Advanced NSCLC has a poor prognosis, with standard chemotherapy drugs having limited effect and adverse side effects are common. Immune checkpoint inhibitor (ICI) treatment has improved overall survival and progression-free survival when used for patients with NSCLC that does not have a driver mutation, particularly when used concomitantly with platinum-based chemotherapy as a first-line treatment. In stage IV NSCLC, pembrolizumab, nivolumab, and atezolizumab have gained approval for use in first- and second-line treatment. However, ICIs cause immune-related adverse events (IRAEs) in up to 70% of patients due to inflammation and tissue damage along with autoimmune activity. An analysis of 63 patients with inoperable NSCLC who underwent immunotherapy over a 24-month period was published on real-life experiences of immunotherapy-related rare toxicities. Most patients had metastatic NSCLC, with 5 patients having unresectable advanced stage III NSCLC.

The patients were categorized according to the type of treatment they received. Group A consisted of 38 patients who received first-line treatment of 200 mg pembrolizumab every 21 days. Group B consisted of 20 patients who received first-line platinum-based chemotherapy and second-line therapy of 200 mg pembrolizumab every 21 days or 240 mg nivolumab every 14 days or 800 mg atezolizumab every 14 days. Group C’s 5 patients had unresectable advanced stage III NSCLC and received concomitant or sequential radio-chemotherapy plus 1500 mg durvalumab every 14 days. All study participants had ≥3 courses of immunotherapy.

IRAEs occurred in 42 patients, with 33 being grades 1 or 2 and 9 being grades 3 or 4. The most commonly reported adverse events were gastrointestinal, dermatological, and thyroid related. No deaths were attributed to the IRAEs. Grade 2 IRAEs were treated with low doses of steroids. Grade 3 IRAEs were treated with high-dose steroids, treatment discontinuation, and treatment directed at the specific organ affected. When toxicity resolved and re-evaluation was performed, ICI treatment was resumed after an average of 2 weeks.

Evaluation of severe IRAEs found 2 patients experienced bowel perforations that required them to undergo Hartmann’s resections. Only 1 patient resumed immunotherapy after surgery. Severe elevation of transaminase was found in 2 patients, and 1 of these patients also developed chronic renal insufficiency. All 3 patients discontinued ICI therapy. Pericardial effusions were found in 2 patients, 1 of which developed cardiac tamponade requiring permanent discontinuation of immunotherapy and pericardiocentesis.

Although most IRAEs were mild, a few patients had serious, life-threatening adverse events requiring immune checkpoint discontinuation and further intervention.

Source

Divisi D, De Vico A, Zaccagna G, et al. NSCLC immunotherapy and related rare toxicities: a monocentric real-life experience. Cancer Med J. 2021;4:115-119.