Efficacy of patritumab deruxtecan on brain metastases in non-small-cell lung cancer carcinoma

After positive results in breast cancer patients, new data from the TUXEDO-3 phase 2 recently published on The Lancet Oncology confirm a promising clinical activity for patritumab deruxtecan (HER3-DXd) on brain metastases in non-small-cell lung cancer (NSCLC) carcinoma too.

For this part of the TUXEDO-3 phase 2 trial, 20 patients with NSCLC and radiologically documented metastatic disease, newly diagnosed brain metastases or progressing brain metastases after local treatment, at least one brain lesion and no need for immediate local therapy, were enrolled and treated with HER3-DXd once every 3 weeks. As authors point out, «HER3, a member of the EGFR family that is implicated in treatment resistance through the activation of downstream signalling pathways, has been found in NSCLC regardless of the mutational status and in more than 70% of NSCLC brain metastases. HER3-DXd has shown promising objective response rates in heavily pretreated patients with EGFR-mutated NSCLC, but no data were currently available on the efficacy of HER3-DXd in active brain metastases of advanced NSCLC». After a median follow-up of 5.3 months, 30% of patients had intracranial responses; treatment-related adverse events occurred i80% of patients, the most common of which were nausea, diarrhea and asthenia; no new safety signals were identified. «The study shows a clinically relevant intracranial and extracranial objective response rate, clinical benefit rate, and disease control rate in patients with or without activating driver mutations», authors say. «Furthermore, the observed survival rates are promising and are accompanied by a tolerable safety profile and stabilization of neurological function and quality-of-life parameters in this pretreated and high-risk population. Finally, exploratory analyses done within the TUXEDO-3 trial indicate that HER3 tissue expression might not be a suitable predictive biomarker for HER3-DXd activity». Authors thus conclude that «The prospective findings of the TUXEDO-3 trial support the use of HER3-DXd in patients with NSCLC and active brain metastases, once this drug is approved for the therapy of metastatic NSCLC. Notably, its intracranial efficacy is not restricted to patients with EGFR-mutated disease. Therefore, future trials should investigate HER3-DXd in a broader population».