Expert oncologist Helena Yu, MD, reviews data from HERTHENA-Lung01 following the IASLC 2023 World Conference on Lung Cancer and considers how patritumab deruxtecan will fit into clinical practice.
Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01
Background
EGFR-activating mutations occur in 14% to 38% of patients with NSCLC
Salvage therapies after EGFR TKI therapy and platinum-based chemotherapy provide only limited and transient clinical benefit
CNS metastases are common in this population, and therapies to ensure CNS control are needed
A phase 1 study of HER3-DXd for advanced NSCLC demonstrated efficacy in patients with EGFR-activating mutations and diverse mechanisms of resistance to EGFR TKIs
Promising data from the phase 1 trial led to initiation of the phase 2 HERTHENA-Lung01 trial of HER3-DXd in patients with EGFR-mutated NSCLC who were treated previously with EGFR TKI and platinum-based chemotherapy
Study Design
Patient population had advanced EGFR-mutated NSCLC
Progression on most recent systemic therapy
Prior EGFR TKI and prior platinum-based chemotherapy
Inactive or previously treated asymptomatic brain metastases allowed
Pretreatment tumor tissue required
R1:1 to fixed dose HER3-DXd IV Q3W or HER3-DXd uptitration
Primary endpoint was cORR by BICR
Key secondary endpoint was DOR by BICR
Results/Conclusions
Clinically meaningful efficacy was observed in the overall population and across subgroups
The safety profile of HER3-DXd was manageable and tolerable and consistent with previous reports
HER3-DXd emerged as a promising therapy for patients with EGFR-mutated NSCLC after the failure of EGFR TKI and platinum-based chemotherapy, for whom available treatment options provide only limited efficacy