Related Experiment Video
Updated: Jul 4, 2026
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Molecular tumor board-guided osimertinib therapy in EGFR L858R/Q701L-mutant lung adenocarcinoma supported by
Corinna Albers-Leischner1, Matthias Ritgen2, Finn-Ole Paulsen1
1Department of Medicine II (Oncology, Hematology, Bone Marrow Transplantation with Section Pneumology) and University Cancer Center (UCC) Hamburg, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Background:
Rare or compound EGFR variants in non-small-cell lung cancer (NSCLC) can create substantial therapeutic uncertainty, particularly when accompanied by additional co-alterations with potential resistance implications. In such settings, molecular tumor boards (MTBs) may integrate genomic, functional, and clinical data to guide treatment selection.
Case Presentation:
A 59-year-old Caucasian woman was diagnosed with metastatic lung adenocarcinoma involving the lungs, bones, and lymph nodes. Histopathology showed a TTF-1 positive pulmonary adenocarcinoma with low PD-L1 expression.
Molecular Findings:
Next-generation sequencing identified a compound EGFR alteration consisting of L858R and Q701L, along with additional alterations in PIK3CA, ATM, and CTNNB1 and loss of CDKN2A/B, MLH1, and BAP1.
Functional And Molecular Tumor Board Assessment:
To resolve this uncertainty, the EGFR mutations were recreated in vitro and characterized within national Network Genomic Medicine (nNGM) preclinical platform. In Ba/F3 models, the EGFR L858R/Q701L co-mutation showed sensitivity to first-, second-, and third-generation EGFR tyrosine kinase inhibitors. After integrating the molecular profile, functional data, and clinical context, the institutional MTB recommended in-label therapy with Osimertinib.
Outcome:
Treatment resulted in rapid clinical improvement and a radiologically confirmed partial remission followed by durable disease control for 18 months. Disease progression occurred thereafter, and the patient died 23.4 months after initial diagnosis.
Conclusion:
This case highlights the importance of functional validation and multidisciplinary tumor board discussion in interpreting complex genomic profiles and guiding personalized therapy in NSCLC.
Insights
This non-small cell lung cancer (NSCLC) case demonstrates how functional validation and molecular tumor boards (MTBs) can guide personalized therapy for complex EGFR mutations. Osimertinib provided durable disease control for 18 months.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Rare or compound epidermal growth factor receptor (EGFR) variants in non-small cell lung cancer (NSCLC) present therapeutic challenges.
- Co-alterations can imply resistance, necessitating integrated data analysis.
Purpose of the Study:
- To investigate the therapeutic implications of a complex EGFR mutation profile in metastatic lung adenocarcinoma.
- To evaluate the utility of functional validation and molecular tumor board (MTB) assessment in guiding treatment decisions.
Main Methods:
- Next-generation sequencing identified compound EGFR mutations (L858R/Q701L) with additional genomic alterations.
- EGFR mutations were recreated in vitro and tested in preclinical models.
- An institutional MTB integrated genomic, functional, and clinical data to recommend therapy.
Main Results:
- The EGFR L858R/Q701L co-mutation demonstrated sensitivity to multiple generations of EGFR tyrosine kinase inhibitors.
- In-label Osimertinib therapy led to rapid clinical improvement and 18 months of durable disease control.
- The patient ultimately progressed and died 23.4 months post-diagnosis.
Conclusions:
- Functional validation and multidisciplinary MTB discussion are crucial for interpreting complex genomic profiles in NSCLC.
- Personalized therapy guided by integrated data can achieve significant disease control in challenging cases.
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