What question did this study set out to answer?

This report aims to highlight the response of a non-small cell lung cancer patient with an EGFR D770_N771insG mutation to osimertinib.

May 20, 2026

C79-12 Non-small Cell Lung Cancer With EGFR D770ₙ771insg Demonstrating an Extended Response to Osimertinib: Case Report

Key Points

This report aims to highlight the response of a non-small cell lung cancer patient with an EGFR D770_N771insG mutation to osimertinib.
Patient presented with worsening symptoms and was diagnosed with lung adenocarcinoma via biopsy.
Next-generation sequencing identified an EGFR D770_N771insG mutation, and the patient was treated with osimertinib off-label.
Progression-free survival and side effects were monitored over an 11-month period.
Patient showed a 35% reduction in tumor burden after 8 weeks of osimertinib treatment with grade 1 toxicity.
Disease control was maintained for 11 months before progression necessitated chemotherapy.
Case contributes to the limited evidence of osimertinib efficacy in specific exon 20 mutations.

Abstract

Abstract Introduction Lung cancer remains the leading cause of cancer-related death worldwide. GLOBOCAN 2022 estimates ∼2. 48 million new cases and 1. 82 million deaths. Non-small-cell lung cancer (NSCLC) comprises ∼85% of cases. Routine genotyping has shifted care toward personalized therapy. Third-generation EGFR inhibitors, notably Osimertinib, are standard first-line treatment for tumors with exon 19 deletions or exon 21 L858R substitutions. In the phase III FLAURA trial, Osimertinib nearly doubled progression-free survival (18. 9 vs 10. 2 months) and improved overall survival versus earlier TKIs. EGFR exon 20 insertions constitute a biologically distinct subgroup (1-2% of NSCLC). Retrospective data show modest activity for Osimertinib monotherapy (PFS 2. 3-3. 6 months; ORR 5-6%), underscoring the need for variant-specific strategies. Case Presentation A 63-year-old non-smoker female presented with worsening dyspnea and cough. Chest CT showed a right upper-lobe mass, mediastinal lymphadenopathy, and scattered bilateral pulmonary nodules, without extrathoracic disease. Bronchoscopic biopsy confirmed lung adenocarcinoma, positive for TTF-1 and Napsin A. Next-generation sequencing identified an EGFR D770N771insG exon 20 insertion; ALK, ROS1, and KRAS were wild type, and the PD-L1 tumor proportion score was 1%. As no approved targeted option was available for this mutation at the time, she began off-label Osimertinib 80 mg daily. After eight weeks, CT imaging showed 35% reduction in tumor burden, accompanied by symptom relief. Toxicities were limited to grade 1 rash and diarrhea. Disease control was maintained for 11 months before radiographic progression prompted a transition to platinum-pemetrexed chemotherapy. Discussion Exon 20 insertions remain a challenging subset of EGFR mutations. Their position within the loop region of the tyrosine kinase domain alters the drug-binding pocket and limits activity of first- and second-generation TKIs. Amivantamab combined with platinum-pemetrexed chemotherapy is currently the most effective first-line option, with a reported progression-free survival of approximately 11. 4 months, and newer TKIs—including Sunvozertinib and CLN-081—are under investigation. Previous reports include a patient with the same D770N771insG variant who experienced disease control beyond two years on first-line Osimertinib, and another case describing a complete radiographic response with the related D770N771insSVD insertion. While most exon 20 insertions confer resistance to approved EGFR TKIs, select variants near codons 770-771 may retain partial sensitivity. Our patient achieved an 11-month response to standard-dose Osimertinib, adding to a small number of encouraging reports. In settings where exon 20-specific inhibitors are unavailable, a carefully monitored trial of Osimertinib may be reasonable. Continued molecular profiling and reporting of rare responders are needed to refine mutation-specific treatment strategies. This abstract is funded by: None

Mark Helpful

Bookmark

Relay