Dr McArthur on Monitoring for ILD When Administering T-DXd in HER2+ Breast Cancer

"[Treatment with T-DXd] has to be a risk;benefit calculation that's individualized to the patient, with increased patient engagement in those decisions.”

Heather McArthur, MD, the Komen Distinguished Chair in Clinical Breast Cancer Research and professor in the Department of Internal Medicine at UT Southwestern Medical Center, as well as clinical director of the Breast Cancer Program at Simmons Cancer Center at UT Southwestern, discussed the clinical importance of vigilant monitoring for interstitial lung disease (ILD) in patients with HER2-positive breast cancer treated with fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu).

T-DXd has emerged as a key component of therapy in advanced setting for patients with HER2-positive breast cancer. With the agent now being investigated in the frontline setting during the phase 3 DESTINY-Breast09 trial (NCT04784715), this has underscored the need for proactive surveillance for treatment-related ILD and pneumonitis, which remain known and potentially serious adverse effects (AEs) associated with T-DXd, McArthur said. In DESTINY-Breast09, the rate of any-grade, drug-related ILD/pneumonitis was 12.1% in patients treated with the combination of T-DXd and pertuzumab (Perjeta; n = 387). Although the majority of these toxicities were grade 1 or 2, 2 patients (0.5%) experienced grade 5 ILD/pneumonitis. There were no grade 3 or 4 instances reported. In contrast, patients treated with trastuzumab (Herceptin) pertuzumab, and a taxane (n = 382) experienced an any-grade, drug-related ILD/pneumonitis rate of 1.0%, with all instances being grade 1 or grade 2 (0.5% each).

McArthur highlighted the importance of recognizing early-stage, asymptomatic ILD (grade 1) to enable timely intervention and mitigate the risk of disease progression to higher-grade pulmonary toxicity. The incorporation of routine imaging—such as high-resolution CT scans—and symptom review remains central to management. Patient education plays a critical role, particularly in ensuring that patients report new respiratory symptoms promptly and understand the potential risks of treatment-related pulmonary toxicities.

Given these risks, McArthur advocated for an individualized risk-benefit assessment when selecting a T-DXd–based regimen, particularly in populations with preexisting pulmonary comorbidities or other risk factors for ILD. She noted that although the therapeutic efficacy of T-DXd supports its use in appropriately selected patients, shared decision-making and increased patient engagement are essential to balancing treatment benefits with the potential for serious adverse events.