Assessing Factors Predictive of Pneumonitis Development with Use of Targeted Therapies in Non–Small-Cell Lung Cancer

Lung cancer has the highest rate of mortality among all cancer types in the United States. Metastases are found in 57% of patients at diagnosis, with a 5% 5-year survival rate. Non–small-cell lung cancer (NSCLC) compromises 85% of all lung cancer cases. There have been recent approvals of therapies targeting NSCLC, including immune checkpoint inhibitors and third-generation tyrosine kinase inhibitors. Although the use of these therapies has improved survival rates over conventional chemotherapy, they have also been associated with serious adverse events, including fatal pneumonitis. Pneumonitis symptoms associated with the use of targeted NSCLC therapies include cough, chest pain, dyspnea, fever, and hypoxia. This NSCLC therapy-related adverse event has been found in patients treated with anaplastic lymphoma kinase inhibitors, epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors, and programmed cell death 1/programmed death-ligand 1 immune checkpoint inhibitors. The majority of patients who develop therapy-related pneumonitis respond to the use of oral corticosteroids, but 1% of patients develop serious grade 3 or 4 pneumonitis. To estimate the incidence of, and the predictors of, treatment-related pneumonitis, Tyczynski and colleagues performed a real-world study using the electronic health records of 81,628 patients with NSCLC treated from 2008 to 2018. Males compromised 49% of the study cohort, 85% were Caucasian, and 46.9% resided in the Midwest. The mean patient age was 69 years at diagnosis. Localized disease was found in 60% of the patients and 38.3% were EGFR-positive.

When line of therapy (LOT) was evaluated, 21.7% of patients had ≥1 LOTs, 8.8% had ≥2 LOTs, and 3.8% had ≥3 LOTs. Pneumonitis developed in 19.0% of treated patients during any LOT, in 26.2% of those patients with a prior history of pneumonitis, and in 17.0% of those patients without a history of pneumonitis. There were 16 risk factor variables examined in this study. Those associated with significantly higher risk of developing pneumonitis included male gender, EGFR-negative status, squamous histology, prior radiation therapy, and immunomodulatory monotherapy treatment. These real-world findings on pneumonitis associated with use of targeted NSCLC therapies may direct future research, improve clinical outcomes in patients with NSCLC, and help clinicians direct therapy to reduce the occurrence of pneumonitis.

Source

Tyczynski JE, Potluri R, Kilpatrick R, et al. Incidence and risk factors of pneumonitis in patients with non-small cell lung cancer: an observational analysis of real-world data. Oncol Ther. 2021;9:471-488.