Diagnosis of drug-induced interstitial lung disease (DILD) in early-phase oncology clinical trials is complicated by its variable onset and diverse clinical and radiological findings, according to a recent study.

DILD, also called pneumonitis, can be a life-threatening toxicity of anticancer treatments. To better understand the clinical and radiological features of DILD, researchers looked at 2499 consecutive patients with advanced cancers who were enrolled in phase 1 clinical trials.

The study revealed that 2.4% of patients developed DILD with a median time to onset of 63 days. Time to onset ranged from 14 days to 336 days. Almost half (45%) of patients who developed DILD were clinically asymptomatic.

DILD occurred most often in patients who receiving drug conjugates (7.4%) followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). Incidence was highest in patients with breast cancer (5.7%) followed by lung cancer (3.8%) and patients with gynecologic tumors (3.6%).


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Hypersensitivity pneumonitis was most common (33.3%), followed by nonspecific interstitial pneumonia (30%) and cryptogenic organizing pneumonia (26.7%).

“[Computed tomography] patterns were consistent throughout the patient’s clinical course in all cases,” the researchers noted. “The different [computed tomography] patterns of DILD showed significant associations with the severity of clinical symptoms as per [Common Terminology Criteria for Adverse Events] grading.”

The researchers also found that higher the DILD score (odds ratio, [OR], 1.47; 95% CI, 1.19-1.81; P <.001) and the pattern of DILD (OR, 5.83; 95% CI, 0.38-90.26; P =.002) were significantly associated with a higher Common Terminology Criteria for Adverse Events grading. The researchers found that the only predictive factors for improvement in DILD was an interruption of treatment (OR, 0.5; 95% CI, 0.01-0.35; P =.01).

“Microbiological testing was undertaken in all of our patients, most commonly in the form of sputum cultures, and blood or urine samples for [polymerase chain reaction]. These tests were negative in the majority of patients,” the researchers wrote. “With the increasing number of complex combinations of novel agents being tested, this study provides a benchmark for the development of a well-defined algorithm for the management of DILD in the early-phase clinical setting.”

Reference

Terbuch A, Tiu C, Candilejo IM, et al. Radiological patterns of drug-induced interstitial lung disease (DILD) in early-phase oncology clinical trials. Clin Cancer Res. Published August 12, 2020. doi:10.1158/1078-0432.CCR-20-0454