TOPLINE:

In a secondary analysis, trastuzumab deruxtecan (T-DXd) demonstrated meaningful systemic responses in patients with ERBB2-mutant non-small cell lung cancer (NSCLC) with or without brain metastases. T-DXd also demonstrated intracranial effectiveness in patients with baseline brain metastases, with most patients experiencing a reduction in brain lesion size.

METHODOLOGY:

• Patients with ERBB2-mutant NSCLC may be at a higher risk of developing brain metastases, which are associated with worse survival. T‑DXd, the first approved ERBB2‑directed antibody-drug conjugate for patients with previously treated unresectable or metastatic ERBB2-mutant NSCLC, could help manage brain metastases in this patient population.
• In the current trial, researchers evaluated T-DXd safety and effectiveness in this patient population with or without baseline brain metastases. The team pooled patient-level data from two phase 2 trials (DESTINY‑Lung01 and DESTINY‑Lung02).
• The trial included 243 patients with previously treated unresectable or metastatic ERBB2-mutant NSCLC who received intravenous T‑DXd every 3 weeks at either 5.4 mg/kg or 6.4 mg/kg. Patients with measurable (≥ 10 mm) or nonmeasurable (< 10 mm) brain metastases or no brain metastases at baseline were included.
• Overall, 102 patients received T‑DXd at 5.4 mg/kg, 31% of whom had brain metastases at baseline; 141 patients received T‑DXd at 6.4 mg/kg, 38% of who had brain metastases at baseline. Approximately half of patients with brain metastases at baseline received prior treatment for these metastases: 53% in the 5.4-mg/kg group and 44% in the 6.4-mg/kg group.

TAKEAWAY:

• In the T-DXd 5.4-mg/kg group, systemic confirmed objective response rates were 47% in patients with brain metastases and 50% in those without brain metastases. In the T-DXd 6.4-mg/kg group, the rates were 50% and 59%, respectively. Median duration of response was shorter in patients with vs without brain metastases (median durations, 4.6 months vs 16.8 months for the 5.4-mg/kg group and 7.2 months vs 14.1 months for the 6.4-mg/kg group).
• Among patients with measurable brain metastases at baseline, intracranial confirmed objective response rates were 50% with the 5.4-mg/kg dose and 30% with the 6.4-mg/kg dose. The median intracranial duration of response was 9.5 months in the 5.4-mg/kg group and 4.4 months in the 6.4-mg/kg group, with at least 78% of patients experiencing reductions in the size of brain lesions.
• As expected, progression-free survival (PFS) and overall survival were shorter among patients with brain metastases than in those without. Median PFS was 7.1 months at both doses in patients with brain metastases compared with 18.0 months at the lower dose and 11.9 months at the higher dose in those without brain metastases. Overall survival duration was 13.6 vs 19.5 months at the lower dose and 13.8 vs 27.9 months at the higher dose in those with vs without brain metastases.
• The most common treatment‑emergent adverse events of grade 3 or higher were neutropenia, vomiting, decreased neutrophil count, and hypokalemia in the 5.4-mg/kg group and decreased neutrophil count, anemia, and nausea in the 6.4-mg/kg group.

IN PRACTICE:

This analysis “showed the effectiveness of T-DXd monotherapy in patients with previously treated ERBB2-mutant metastatic NSCLC, regardless of whether brain metastases were present at baseline,” the authors concluded. “Additionally, T-DXd demonstrated intracranial effectiveness among patients with baseline brain metastases.”

SOURCE:

The study, led by Pasi A. Jänne, MD, PhD, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, was published online in JAMA Network Open.

LIMITATIONS:

The exploratory and retrospective design, small sample size, and lack of a comparator arm limited result interpretation. Patients with symptomatic or untreated brain metastases requiring steroids or anticonvulsants were excluded, limiting generalizability to those with less aggressive central nervous system disease. Additionally, the lack of serial brain imaging in patients without brain metastases at baseline may have resulted in underestimating intracranial progression, while the heterogeneity of prior local brain metastasis treatments complicated attributing benefits exclusively to T-DXd. 

DISCLOSURES:

This study was supported by Daiichi Sankyo, Inc. Three authors reported being employees of or holding stocks with Daiichi Sankyo. Several authors reported receiving grants or personal fees from and having other ties with various sources. Full disclosures are noted in the original article.

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