ILD Seen in Some Taking ADC for Brain Cancer Metastases

TOPLINE:

In patients with HER2-positive breast cancer brain metastases, treatment with trastuzumab deruxtecan was associated with a 10% incidence rate of interstitial lung disease (ILD)/pneumonitis, with 2% of patients experiencing events of grade 3 or higher and 11% discontinuing treatment. Although no fatal lung complications occurred, the findings highlight the need for careful monitoring in this high-risk population.

METHODOLOGY:

HER2-positive breast cancer frequently metastasizes to the brain, and prior HER2-directed therapies have shown limited intracranial activity. Trastuzumab deruxtecan, a next-generation antibody-drug conjugate, has demonstrated marked intracranial benefits but carries a risk for ILD/pneumonitis. Previous studies have analyzed its safety profile in the general HER2-positive population but have not specifically analyzed outcomes in patients with breast cancer brain metastases.
To address this gap, researchers conducted a systematic review and meta-analysis of nine studies involving 684 patients with HER2-positive breast cancer brain metastases. Most studies included patients with a median age of 51-55 years; 63% had hormone receptor-positive tumors, and the mean follow-up duration was 16 months.
Study outcomes were occurrences of various treatment-emergent adverse events (TEAEs) associated with trastuzumab deruxtecan, with a specific focus on the incidence and severity of ILD/pneumonitis.

TAKEAWAY:

The pooled incidence rates of ILD/pneumonia of all grades and grade 3 or higher were 10% (95% CI, 5%-16%) and 2% (95% CI, 1%-4%), respectively; ILD/pneumonitis prompted treatment discontinuation in 11% (95% CI, 0%-24%) of patients.
Overall, TEAEs occurred in 97% of patients, with events of grade 3 or higher occurring in 48%. Fatigue and nausea were the most common all‐grade TEAEs, occurring in 67% and 60% of patients with breast cancer brain metastases, respectively.
The rate of any fatal TEAEs was 1% (95% CI, 0%-4%). No fatal cases of ILD/pneumonitis were reported in the analyzed cohort, which is “in…contrast to the 2.3% fatal ILD/pneumonitis rate documented in the [breast cancer brain metastasis] cohort of DESTINY-Breast12,” the authors wrote.
Subgroup analyses suggested higher rates of all-grade ILD/pneumonia and higher rates of events of grade 3 or higher in 2024 studies; however, none of these subgroup differences reached statistical significance.

IN PRACTICE:

“This meta‐analysis provides essential safety data specific to this population, confirming that ILD/pneumonitis remains a prevalent and clinically significant TEAE, leading to treatment discontinuation in a fraction of patients,” the authors wrote. Although no fatal ILD events were observed, “the potential association between [brain metastasis] and heightened susceptibility to ILD/pneumonitis highlights the essential need for vigilant monitoring and proactive management to improve survival outcomes in these patients.”

SOURCE:

The study, led by Yiwen Ma, PhD, Cancer Hospital of Dalian University of Technology, Shenyang, China, was published online in Cancer.

LIMITATIONS:

The included studies were predominantly retrospective or subgroup analyses of larger trials, which might have introduced potential selection bias in ILD/pneumonitis monitoring and management protocols. The analysis showed moderate-to-high heterogeneity in pooled estimates, whereas some studies had relatively short median follow-up times that might have underestimated late-onset ILD/pneumonitis events. Additionally, potential confounding factors such as brain metastases activity, proportion of lung metastases, and prior anti-HER2 treatment strategies could not be assessed through subgroup analysis due to inconsistent reporting across studies.

DISCLOSURES:

The study received support from multiple grants, including Liaoning Provincial Key R&D Projects, Shenyang Public Health R&D Special Project, Shenyang Breast Cancer Clinical Medical Research Center (2020-48-3-1), Liaoning Province Joint Fund Project, and Liaoning Cancer Hospital Oncology+ Project. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.