Treatment Considerations for Patients With Small Cell Lung Cancer, Pre-Existing Interstitial Lung Disease

At the World Conference on Lung Cancer 2024 in San Diego, California, Daichi Fujimoto, MD, PhD, from the Hyogo Medical University in Japan shared treatment considerations for individuals diagnosed with small cell lung cancer (SCLC) with pre-existing interstitial lung disease (ILD)—emphasizing the importance of chemoimmunotherapy as a safe and effective treatment option.

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Fujimoto noted that ILD is characterized by damage to the lung structure caused by inflammation and fibrosis, which can be detected through imaging tests like CT scans. Additionally, ILD includes a wide range of patterns, but fibrotic ILD, particularly idiopathic pulmonary fibrosis (IPF), has been shown to be associated with an increased risk of lung cancer. According to previous reports, whether in early stage or advanced cases, nearly 10% of lung cancer patients also have coexisting ILD.

“It is very common to encounter lung cancer patients with ILD in clinical practice. It is crucial to distinguish between patients with ILD and adults without it. This distinction is important because the risk of severe pneumonitis induced by cancer treatment is significantly higher in patients with ILD,” Fujimoto said.

Severe pneumonitis, also known as acute exacerbation of ILD can be triggered by cancer treatment, occurring often among patients. Due to the elevated risk of pneumonitis, patients with ILD are often excluded from clinical trials. Fujimoto noted that because of this, the standard cancer treatments may differ between lung cancer patients with or without ILD. Additionally, individuals with “honeycomb lung”—the presence of destroyed and fibrotic lung tissue holding cystic airspaces with thick fibrous walls along with reduced lung function, face a particularly high risk of developing pneumonitis.

Immune checkpoint inhibitors (ICIs) are currently used as the standard first line therapy to treat lung cancer as chemoimmunotherapy is the standard treatment among individuals with extensive SCLC, Fujimoto noted. However, the potential risks and benefits of immunotherapy should be discussed with patients that have pre-existing ILD and some ICIs are not recommended in many countries. Research has displayed that the frequency of ICI-related pneumonitis is higher among individuals with lung cancer with ILD, compared to individuals without ILD, Fujimoto noted.

To assess these therapies, the phase 2 AMBITIOUS trial was the first known study that assessed the safety and efficacy of atezolizumab among individuals with non-squamous lung cancer with pre-existing ILD. Fujimoto noted that the trial was terminated early due to a high incidence of pneumonitis, with 30% of patients developing pneumonitis, and all cases with honeycomb lung being severe. Additionally, the IDL-NIVO trial investigated whether chemo-immunotherapy could be safely used in patients with extensive stage small cell lung cancer and mild ILD who meet the HAV criteria—of having honeycomb lung, auto-antibodies and a vital capacity less than 80%. Fujimoto provided that the trial met its predefined primary endpoint with only one case of severe pneumonitis, suggesting that chemo-immunotherapy could be a potential option for this specific patient population.

“ILD patients face significant risk of pneumonitis with cancer treatments. However, with careful selection based on ILD status, chemoimmunotherapy can be safe and effective among pre-existing ILD patients,” said Fujimoto.

REFERENCE

Fujimoto D. Novel Immunotherapy Options for Patients With Neuroendocrine Tumors, Treatment Considerations for Patients diagnosed with Small Cell Lung Cancer with Pre-existing ILD. 2024 World Conference on Lung Cancer, San Diego, California. Presented September 9, 2024. Accessed online September 12, 2024.