Radiological Patterns of Drug-induced Interstitial Lung Disease (DILD) in Early-phase Oncology Clinical Trials

• Published in: Clinical cancer research 2020-09, Vol.26 (18), p.4805-4813
• Main Authors: Terbuch, Angelika, Tiu, Crescens, Candilejo, Irene Moreno, Scaranti, Mariana, Curcean, Andra, Bar, Dan, Estevez Timon, Miriam, Ameratunga, Malaka, Ang, Joo Ern, Ratoff, Jonathan, Minchom, Anna R, Banerji, Udai, de Bono, Johann S, Tunariu, Nina, Lopez, Juanita S
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Agents - adverse effects; Clinical Trials, Phase I as Topic; Female; Humans; Incidence; Lung - diagnostic imaging; Lung - drug effects; Lung Diseases, Interstitial - chemically induced; Lung Diseases, Interstitial - diagnosis; Lung Diseases, Interstitial - epidemiology; Male; Middle Aged; Neoplasm Staging; Neoplasms - diagnosis; Neoplasms - drug therapy; Time Factors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-20-0454

Drug-induced interstitial lung disease (DILD) is a rare, but potentially fatal toxicity. Clinical and radiological features of DILD in the early experimental setting are poorly described. A total of 2,499 consecutive patients with advanced cancer on phase I clinical trials were included. DILD was identified by a dedicated radiologist and investigators, categorized per internationally recognized radiological patterns, and graded per Common Terminology Criteria for Adverse Events (CTCAE) and the Royal Marsden Hospital (RMH) DILD score. Clinical and radiological features of DILD were analyzed. Sixty patients overall (2.4%) developed DILD. Median time to onset of DILD was 63 days (range, 14-336 days). A total of 45% of patients who developed DILD were clinically asymptomatic. Incidence was highest in patients receiving drug conjugates (7.4%), followed by inhibitors of the PI3K/AKT/mTOR pathway (3.9%). The most common pattern seen was hypersensitivity pneumonitis (33.3%), followed by nonspecific interstitial pneumonia (30%), and cryptogenic organizing pneumonia (26.7%). A higher DILD score [OR, 1.47, 95% confidence interval (CI), 1.19-1.81; < 0.001] and the pattern of DILD (OR, 5.83 for acute interstitial pneumonia; 95% CI, 0.38-90.26; = 0.002) were significantly associated with a higher CTCAE grading. The only predictive factor for an improvement in DILD was an interruption of treatment (OR, 0.05; 95% CI, 0.01-0.35; = 0.01). DILD in early-phase clinical trials is a toxicity of variable onset, with diverse clinical and radiological findings. Radiological findings precede clinical symptoms. The extent of the affected lung parenchyma, scored by the RMH DILD score, correlates with clinical presentation. Most events are low grade, and improve with treatment interruption, which should be considered early.