Trastuzumab deruxtecan may lead to interstitial lung disease (ILD)/pneumonitis in a subset of patients with cancer, according to research published in ESMO Open

Researchers pooled data from 9 trials of trastuzumab deruxtecan and found the risk of ILD/pneumonitis was associated with patient age, time since cancer diagnosis, dose of the drug, and other factors.

The analysis included data from phase 1 and 2 trials of trastuzumab deruxtecan monotherapy. The trials encompassed a total of 1150 patients. The patients’ median age was 60 (range, 20-96) years, and 65.7% were women.

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The patients had breast cancer (44.3%), gastric cancer (25.6%), lung cancer (17.7%), colorectal cancer (9.3%), and other cancers (3.0%). They had received a median of 4 prior lines of therapy (range, 1-27). The median duration of trastuzumab deruxtecan treatment was 5.8 (range, 0.7-56.3) months. 

The overall incidence of drug-related ILD/pneumonitis was 15.4%, with 224 events occurring in 177 patients. Most patients had grade 1 (4.2%) or grade 2 (7.7%) ILD/pneumonitis, but grade 3 (1.2%), grade 4 (0.1%), and grade 5 (2.2%) cases were observed as well.

For most patients with ILD/pneumonitis (87.0%), the first event occurred within the first 12 months of treatment. The median time to onset was 5.4 (range, <0.1-46.8) months.

Factors associated with an increased risk of ILD/pneumonitis included:

  • Age younger than 65 years (hazard ratio [HR], 1.56; 95% CI, 1.02-2.38)
  • Trial enrollment in Japan (HR, 2.08; 95% CI, 1.45-2.98)
  • Lung comorbidities (HR, 1.75; 95% CI, 1.03-2.98)
  • A moderate/severe decrease in baseline renal function (HR, 2.73; 95% CI, 1.65-4.52)
  • Cancer diagnosis more than 4 years prior (HR, 1.82; 95% CI, 1.20-2.75) 
  • Trastuzumab deruxtecan dose greater than 6.4 mg/kg every 3 weeks (HR, 2.92; 95% CI, 1.32-6.42)
  • Baseline oxygen saturation less than 95% (HR, 2.14; 95% CI, 1.11-4.13).

“Specific risk factors should be confirmed in ongoing and future trials,” the researchers wrote. “Phase III randomized controlled trials across multiple tumor types and in earlier lines of therapy are ongoing, and this analysis further supports the benefit-risk profile of T-DXd [trastuzumab deruxtecan] in advanced cancer.”

Disclosures: This research was supported by AstraZeneca Pharmaceuticals and Daiichi Sankyo Company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.  


Powell CA, Modi S, Iwata H, et al. Pooled analysis of drug-related interstitial lung disease and/or pneumonitis in nine trastuzumab deruxtecan monotherapy studies. ESMO Open. Published online August 10, 2022. doi:10.1016/j.esmoop.2022.100554