Dr Herbst on the Evolution of Targeted Therapies for EGFR+ NSCLC

Roy S. Herbst, MD, PhD, Ensign Professor of Medicine (Medical Oncology), professor, pharmacology, deputy director, Yale Cancer Center; chief, Medical Oncology, director, Center for Thoracic Cancers, Yale Cancer Center and Smilow Cancer Hospital; assistant dean, Translational Research, Yale School of Medicine, discusses the evolution of targeted therapies for patients with EGFR-mutated non–small cell lung cancer (NSCLC), as well as hurdles associated with biomarker testing in NSCLC.

The exploration of targeted therapies in early-stage NSCLC, particularly for patients with EGFR mutations, has shown promising results, Herbst begins. According to Herbst, EGFR mutations have similar prevalence in early and late disease stages. They are present in approximately 10% to 15% of patients with NSCLC in the United States and 25% to 30% of those in Asia, he adds. The phase 3 ADAURA trial (NCT02511106) demonstrated that adjuvant osimertinib (Tagrisso) administered for 3 years following complete resection in patients with stage IB to IIIA NSCLC with EGFR exon 19 or 21 mutations significantly improved disease-free survival and reduced the risk of death by 51% (HR, 0.49; 95.03% CI, 0.34-0.70; P < .001) compared with placebo. These data support the use of targeted therapies in early disease settings, potentially preventing the emergence of treatment resistance, Herbst says. The phase 3 ALINA trial (NCT03456076), which is examining alectinib (Alecensa) in patients with resected ALK-positive NSCLC, and similar studies in patients with other driver mutations, are anticipated to produce similar findings, Herbst notes.

In studies evaluating minimal residual disease, investigators can use a bespoke model that sequences tumors and monitors mutations via liquid biopsy, Herbst adds. These studies have shown that liquid biopsy can predict disease recurrence earlier than tissue biopsy and suggest that some patients may benefit from prolonged osimertinib treatment, Herbst explains. Osimertinib has also demonstrated efficacy in the treatment of patients with NSCLC and brain metastases, and data from the phase 3 LAURA trial (NCT03521154) have shown the agent’s activity in stage III disease, Herbst emphasizes.

Biomarker testing often includes several challenges, Herbst notes. Adequate tissue or liquid biopsy samples need to be collected at the start of treatment to develop predictive markers of response, Herbst says. Ensuring adequate sample collection, especially in global studies, and obtaining on-treatment biopsies are critical aspects of biomarker testing but are often difficult to achieve due to logistical and procedural hurdles, Herbst emphasizes. Despite these challenges, early implementation of targeted therapies based on biomarker testing results could improve outcomes for patients with NSCLC harboring actionable driver mutations, Herbst concludes.