Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC Following EGFR TKI and Platinum-Based Chemotherapy: HERTHENA-Lung01

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