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Osimertinib for Previously Treated Patients With Advanced EGFR T790M Mutation-Positive NSCLC: Tolerability and
Edgardo S Santos1, Barry Kaplan2, Eli Kirshner3
1Lynn Cancer Institute, Boca Raton, FL, USA. esantos@brrh.com.
Introduction:
The osimertinib (AZD9291) US Expanded Access Program (EAP) provided compassionate access to osimertinib prior to US Food and Drug Administration (FDA) approval for patients with advanced/metastatic epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer (NSCLC) following progression on tyrosine kinase inhibitors (TKIs) targeting EGFR. Here, we report the patient demographics, safety and tolerability, and diagnostic methods used for T790M testing in the EAP.
Methods:
Adult patients with EGFR T790M-positive NSCLC following progression on prior EGFR-TKI therapy (irrespective of line of therapy) were enrolled in the EAP and treated with 80 mg osimertinib once daily until dose reduction, discontinuation, or completion of the EAP following FDA approval (November 2015). Various testing methods were allowed for the required T790M testing.
Results:
In total, 248 patients from 25 centers throughout the USA were enrolled in the EAP. The starting dose of 80 mg osimertinib once daily was maintained for 96% (n = 238) of patients over the duration of the EAP (median duration of exposure 84 days). Most patients (overall 83% [n = 205/238]; patients aged ≥ 75 years 83% [n = 48/58]) completed the EAP and transitioned to commercially available osimertinib following FDA approval. Serious adverse events considered to be treatment related by investigators were reported in five patients (2%), all aged ≥ 65 years, and were dyspnea, deep vein thrombosis, femur fracture, alanine aminotransferase increase, and pneumonitis, respectively. A variety of biospecimen types were collected: solid tumor tissue (73%), blood (20%), cytology (6%), and urine (2%). PCR-based methods were most commonly used for determining EGFR mutation status (47%) followed by next-generation sequencing (33%).
Conclusion:
In a real-world setting, osimertinib was well tolerated, and most patients, including patients aged ≥ 75 years, transitioned to commercially available osimertinib following FDA approval. The EAP suggests there has been an uptake of minimally invasive T790M testing methods at some centers.
Funding:
AstraZeneca (Wilmington, DE, USA).
Insights
Osimertinib was well-tolerated in the US Expanded Access Program for EGFR T790M-positive non-small cell lung cancer patients. Most patients successfully transitioned to commercial osimertinib post-FDA approval, showing good tolerability across age groups.
Area of Science:
- Oncology
- Pharmacology
Background:
- The US Expanded Access Program (EAP) provided early access to osimertinib for advanced/metastatic EGFR T790M-positive non-small cell lung cancer (NSCLC) patients.
- This program offered treatment before US Food and Drug Administration (FDA) approval for patients progressing on EGFR tyrosine kinase inhibitors (TKIs).
Purpose of the Study:
- To report patient demographics, safety, and tolerability of osimertinib within the EAP.
- To evaluate the diagnostic methods employed for T790M mutation testing in this patient cohort.
Main Methods:
- Adult patients with EGFR T790M-positive NSCLC after prior EGFR-TKI therapy were enrolled.
- Treatment involved 80 mg osimertinib once daily until dose modification, discontinuation, or EAP completion post-FDA approval.
- Various testing methods were permitted for T790M detection.
Main Results:
- 248 patients from 25 US centers participated; 96% maintained the starting dose.
- 83% of patients completed the EAP and transitioned to commercial osimertinib, including those aged 75 years and older.
- Serious adverse events (2%) were infrequent and primarily observed in older patients; common T790M testing included PCR (47%) and next-generation sequencing (33%).
Conclusions:
- Osimertinib demonstrated good tolerability and efficacy in a real-world setting for EGFR T790M-positive NSCLC.
- The majority of patients, including the elderly, transitioned to commercial osimertinib, indicating successful program outcomes.
- The EAP highlighted an increasing use of minimally invasive T790M testing methods.
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