HERTHENA-Lung01: HER3-DXd in Previously Treated Advanced EGFR-Mutated NSCLC

EP: 1.PAPILLON: Amivantamab Plus Chemotherapy in EGFR Exon 20 Insertion–Mutated Advanced NSCLC

EP: 2.LIBRETTO-431: Selpercatinib in RET Fusion–Positive NSCLC

EP: 3.MARIPOSA: Amivantamab Plus Lazertinib in EGFR-Mutated Advanced NSCLC

EP: 4.TROPION-Lung05: Dato-DXd in Previously Treated NSCLC

EP: 5.MARIPOSA-2: Amivantamab, Lazertinib, and Chemotherapy in EGFR-Mutated Advanced NSCLC

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EP: 6.HERTHENA-Lung01: HER3-DXd in Previously Treated Advanced EGFR-Mutated NSCLC

EP: 7.Key Data Overview in NSCLC From ESMO 2023

This is a synopsis of a Readout 360 series featuring Sandip P. Patel, MD, of UC San Diego Moores Cancer Center; Joshua K. Sabari, MD, of NYU Langone’s Perlmutter Cancer Center; and Alexander I. Spira, MD, PhD, FACP, of Virginia Cancer Specialists.

Alexander I. Spira, MD, PhD, FACP, from Virginia Cancer Specialists and US Oncology Research, discussed the intracranial efficacy of patritumab deruxtecan (HER3-DXd) in patients with previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC) based on results from the HERTHENA-Lung01 study, presented by Dr. Johnson and colleagues at the European Society for Medical Oncology (ESMO) 2023 conference.

Currently available therapies provide limited benefits for patients with EGFR-mutated NSCLC after failure of tyrosine kinase inhibitors (TKIs) and platinum-based chemotherapy, and many of these patients have central nervous system (CNS) metastases, which portend a poor prognosis. Patritumab deruxtecan is an antibody-drug conjugate consisting of a fully human HER3-directed monoclonal antibody attached to a topoisomerase I payload via a stable tetrapeptide-based cleavable linker. In the phase 2 HERTHENA-Lung01 study, patritumab deruxtecan demonstrated promising activity and safety, including in patients with stable brain metastases.

The study included patients with advanced EGFR-mutated NSCLC who had received prior treatment with osimertinib and at least one platinum-based chemotherapy regimen and had an Eastern Cooperative Oncology Group (ECOG) performance status of 1 or less. Patients were excluded if they had prior treatment with patritumab, active brain metastases, a history of interstitial lung disease (ILD), pneumonitis, or leptomeningeal disease. Patients were randomized to receive patritumab deruxtecan at doses of 5.6 mg/kg or 3.2 mg/kg, with the latter dose subsequently escalated.

The exploratory analysis focused on intracranial response assessed by blinded independent central review using magnetic resonance imaging (MRI) at baseline and every 6 weeks up to week 24. The median treatment duration was 4.2 months, and the median duration of response was 8.5 months. The clinical overall response rate in the CNS by blinded independent central review was 20% overall and 37% in patients who had never received prior radiotherapy to the brain. Sixty percent of patients had a CNS best objective response of stable disease, and 14% had progressive disease. In patients with target lesions, 15 out of 23 had a reduction in the sum of diameters, resulting in an overall response rate of 22%.

Dr. Spira concluded that patritumab deruxtecan demonstrated efficacy in EGFR-mutated NSCLC with CNS metastases, with durable responses. These data add to the growing evidence that systemic treatment is feasible in patients with brain metastases and support further investigation and development of patritumab deruxtecan in this context.

*Video synopsis is AI-generated and reviewed by Cancer Network editorial staff.