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Patritumab deruxtecan (HER3-DXd) may overcome treatment resistance in patients with EGFR-mutant non-small cell lung cancer (NSCLC), according to trial results presented at the 2023 World Conference on Lung Cancer.1
In this phase 2 trial, patritumab deruxtecan provided “clinically meaningful and durable efficacy” in patients whose disease had progressed after treatment with an EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy, said study presenter Helena A. Yu, MD, of Memorial Sloan Kettering Cancer Center in New York, New York.
This trial, HERTHENA-Lung01 (ClinicalTrials.gov Identifier: NCT04619004), included 225 patients with EGFR-mutant NSCLC who had previously received EGFR TKI therapy and platinum-based chemotherapy. Patients’ disease had progressed on their most recent systemic therapy.
The patients had received a median of 3 prior lines of therapy (range, 1-11). Half of patients (51%) had a history of central nervous system metastasis, 32% had brain metastasis at baseline, and 33% had liver metastasis at baseline. The median age was 64 (range, 37-82) years.
The patients received patritumab deruxtecan at 5.6 mg/kg once every 3 weeks. The median follow-up was 18.9 months.
The confirmed objective response rate (ORR) was 29.8%. One patient had a complete response, and 66 patients had a partial response. The median duration of response was 6.4 months. The median progression-free survival (PFS) was 5.5 months, and the median overall survival (OS) was 11.9 months.
In the subset of patients who had previously received a third-generation EGFR TKI, the ORR was 29.2% (1 complete response and 60 partial responses). The median duration of response, PFS, and OS were the same as in the overall cohort.
Dr Yu noted that ORRs were similar regardless of the mechanism of EGFR TKI resistance. The confirmed ORR was 32.4% in patients with EGFR-dependent resistance, 27.2% in patients with EGFR-independent resistance, 37.5% in patients with both types of resistance, and 27.3% in patients who had an unknown mechanism of resistance.
Among patients with measurable brain metastases at baseline and no prior radiotherapy, the confirmed intracranial ORR was 33.3%, with 9 complete responses and 1 partial response. The median duration of intracranial response was 8.4 months.
Dr Yu said safety outcomes in this study were in line with previous results. The rate of treatment-related adverse events (AEs) was 95.6%, and the rate of grade 3 or higher treatment-related AEs was 45.3%. There were 4 fatal AEs related to treatment (pneumonitis, respiratory failure, gastrointestinal perforation, and pneumonia).
The most common treatment-emergent AEs of any grade were nausea (66%), thrombocytopenia (44%), decreased appetite (42%), neutropenia (36%), constipation (34%), anemia (33%), and fatigue (31%).
Patritumab deruxtecan “provided clinically meaningful and durable efficacy with a response rate of 30% in patients with advanced EGFR-mutant non-small cell lung cancer that progressed following EGFR TKI and platinum-based chemotherapy,” Dr Yu concluded. “Efficacy was observed across diverse mechanisms of resistance and across a broad range of pretreatment tumor HER3 expression.”
Results from this trial were also published in the Journal of Clinical Oncology.2
Disclosures: This research was supported by Daiichi Sankyo, Inc. Please see the journal article for a full list of author disclosures.
References
1. Yu HA, Goto Y, Hayashi H, et al. Patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC following EGFR TKI and platinum-based chemotherapy: HERTHENA-Lung01. Presented at WCLC 2023. September 9-12, 2023. Abstract OA05.03.
2. Yu HA, Goto Y, Hayashi H, et al. HERTHENA-Lung01, a phase II trial of patritumab deruxtecan (HER3-DXd) in epidermal growth factor receptor–mutated non–small-cell lung cancer after epidermal growth factor receptor tyrosine kinase inhibitor therapy and platinum-based chemotherapy. J Clin Oncol. Published online September 10, 2023. doi:10.1200/JCO.23.01476
This article originally appeared on Cancer Therapy Advisor
