What is the incidence of pneumonitis in patients treated with durvalumab (Imfinzi)?

From the Guidelines

The incidence of pneumonitis in patients treated with durvalumab (Imfinzi) is approximately 2% to 5%, with severe (Grade 3-4) pneumonitis occurring in about 0.5% to 1.5% of patients, as reported in the most recent study 1.

Incidence of Pneumonitis

The incidence of pneumonitis in patients treated with durvalumab can vary, but the most recent and highest quality study suggests that it ranges from 2% to 5% 1. This is consistent with previous studies that have reported similar incidence rates 1.

Risk Factors

Patients with a history of thoracic radiation, pre-existing lung disease, or prior pneumonitis are at higher risk of developing pneumonitis while on durvalumab 1.

Management

Management of pneumonitis depends on severity, with mild cases potentially managed with observation while continuing durvalumab, whereas moderate to severe cases require treatment interruption and corticosteroids (typically prednisone 1-2 mg/kg/day or equivalent) 1.

Diagnosis

Diagnosis requires exclusion of infectious causes and is often confirmed with chest imaging showing new infiltrates 1.

Immune-Mediated Adverse Effect

Pneumonitis occurs because durvalumab, as a PD-L1 inhibitor, enhances T-cell activity against tumor cells but can also trigger immune responses against normal tissues, including the lungs 1.

• The most common symptoms of pneumonitis include shortness of breath, cough, chest pain, and fever 1.
• Clinicians should monitor patients for these symptoms while on durvalumab 1.
• The incidence of pneumonitis may be higher in patients with non-small cell lung cancer (NSCLC) compared to patients with melanoma 1.

From the FDA Drug Label

In patients who received IMFINZI on clinical studies in which radiation therapy was generally not administered immediately prior to initiation of IMFINZI, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (< 0.1%), and Grade 3-4 (0. 4%) adverse reactions. The incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Immune-mediated pneumonitis occurred in 1. 3% (5/388) of patients receiving IMFINZI in combination with tremelimumab-actl, including fatal (0.3%) and Grade 3 (0. 2%) adverse reactions. Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with tremelimumab-actl and platinum-based chemotherapy, including fatal (0. 5%), and Grade 3 (1%) adverse reactions.

The incidence of pneumonitis in patients treated with durvalumab (Imfinzi) varies depending on the context:

• Without recent prior radiation: 2.4% (34/1414)
• With recent prior radiation in PACIFIC: 18.3% (87/475)
• With recent prior radiation in ADRIATIC: 14% (37/262)
• In combination with tremelimumab-actl: 1.3% (5/388)
• In combination with tremelimumab-actl and platinum-based chemotherapy: 3.5% (21/596) 2

From the Research

Incidence of Pneumonitis in Patients Treated with Durvalumab

• The incidence of pneumonitis in patients treated with durvalumab has been reported in several studies, with varying rates of occurrence 3, 4, 5, 6, 7.
• A retrospective study of 83 patients with stage III non-small cell lung cancer (NSCLC) treated with durvalumab consolidation therapy reported a pneumonitis incidence of 25.3%, with 6% being grade 3/4 3.
• Another study of 107 patients with NSCLC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy followed by durvalumab reported a pneumonitis incidence of 89%, with 53% having grade 1,28% grade 2,6.5% grade 3, and 0.9% grade 4 5.
• A large single-institution analysis of 190 patients with locally advanced NSCLC treated with chemoradiation followed by durvalumab reported a grade 2+ pneumonitis incidence of 26.3%, with a 1-year cumulative incidence of 27.8% 6.
• A real-world study of 284 patients with NSCLC treated with durvalumab following concurrent chemoradiation reported a clinically significant pneumonitis incidence of 21.5%, with 7 patients developing grade 5 pneumonitis (death from pneumonitis) 7.

Risk Factors for Pneumonitis

• Several studies have identified risk factors for pneumonitis in patients treated with durvalumab, including:

• Age ≥70 years, male sex, and V5 ≥58.9% 5.
• Dosimetric predictors such as ipsilateral and total lung volume receiving 5 Gy or greater (V5Gy), V10Gy, V20Gy, V40Gy, and mean dose, as well as contralateral V40Gy and heart V5Gy, V10Gy, and mean dose 6.
• Body mass index (BMI) was found to be a clinical predictor of pneumonitis in one study 7.

Impact of Pneumonitis on Survival

• The impact of pneumonitis on survival in patients treated with durvalumab is not fully understood, with one study reporting no association between the development of pneumonitis and risk of death 7.
• Another study reported a median overall survival (OS) of 27.8 months in patients who developed pneumonitis, compared to 36.9 months in patients who did not develop pneumonitis, although this difference was not statistically significant 7.