OncLive® On Air S16 Ep23: Show Me the Data™: Post-TKI Sequencing in EGFR-Mutated NSCLC—Optimizing Current Strategies and Preparing for New Treatment Modalities
Mar 10, 2026
Xiuning Le, MD, PhD, clinician–scientist in thoracic oncology; Lyudmila Bazhenova, MD, precision medicine–focused medical oncologist; Hossein Borghaei, DO, MS, expert in systemic therapy sequencing. They discuss repeat tissue vs liquid biopsy at progression. They cover optimal NGS approaches, MET amplification detection, small‑cell transformation management, sequencing after osimertinib, bispecific antibodies, VEGF/PD‑1 strategies, and ADC considerations.
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Biopsy At Systemic Progression To Guide Therapy
- Do biopsy progressing lesions when systemic progression occurs to rule out small cell transformation and identify actionable resistance mechanisms.
- Hossein Borghaei emphasizes obtaining tissue when plasma NGS is inconclusive, despite logistical delays of scheduling and testing.
Use Liquid First Then Confirm With Tissue If Needed
- Do obtain both liquid biopsy and tissue biopsy at progression; use tissue when plasma results are inadequate or you suspect transformation.
- Hossein Borghaei reports liquid NGS at diagnosis and progression for everyone but pursues tissue if worried about plasma sensitivity.
Prioritize DNA NGS Then Reflex To RNA For Resistance
- Run DNA-based NGS first on resistant tissue, then reflex to RNA for fusions because resistant biopsies are often small and necrotic.
- Xiuning Le explains institutional workflow: prioritize DNA panel, then RNA if needed to capture fusions.