Related Experiment Video
Updated: Jun 29, 2025
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
Phase II Study of Osimertinib in Patients With Epidermal Growth Factor Receptor Mutations: Results From the NCI-MATCH
Monica F Chen1, Zihe Song2, Helena A Yu1
1Memorial Sloan Kettering Cancer Center, New York, NY.
Purpose:
The National Cancer Institute Molecular Analysis for Therapy Choice trial is a signal-finding genomically driven platform trial that assigns patients with any advanced refractory solid tumor, lymphoma, or myeloma to targeted therapies on the basis of next-generation sequencing results. Subprotocol E evaluated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with EGFR mutations.
Methods:
Eligible patients had EGFR mutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer with EGFR T790M were excluded. The primary end point was objective response rate (ORR), and the secondary end points were 6-month progression-free survival (PFS), overall survival, and toxicity.
Results:
A total of 19 patients were enrolled: 17 were evaluable for toxicity and 13 for efficacy. The median age of the 13 included in the efficacy analysis was 63 years, 62% had Eastern Cooperative Oncology Group performance status 1, and 31% received >three previous systemic therapies. The most common tumor type was brain cancers (54%). The ORR was 15.4% (n = 2 of 13; 90% CI, 2.8 to 41.0) and 6-month PFS was 16.7% (90% CI, 0 to 34.4). The two confirmed RECIST responses were observed in a patient with neuroendocrine carcinoma not otherwise specified (EGFR exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus (EGFR D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash.
Conclusion:
In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with an EGFR exon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with an EGFR D770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.
Insights
Osimertinib showed limited efficacy in pretreated patients with advanced cancers and EGFR mutations, failing to meet primary endpoints. However, notable responses occurred in specific neuroendocrine and epithelial carcinomas, with a manageable safety profile.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- The National Cancer Institute Molecular Analysis for Therapy Choice (NCI-MATCh) trial is a genomically driven platform study for advanced cancers.
- Subprotocol E investigated osimertinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in patients with specific EGFR mutations.
Purpose of the Study:
- To evaluate the efficacy and safety of osimertinib in patients with advanced refractory solid tumors, lymphoma, or myeloma harboring EGFR mutations.
- To determine the objective response rate (ORR) as the primary endpoint.
Main Methods:
- Patients with EGFR mutations (T790M or rare activating mutations), excluding lung cancer with T790M, received osimertinib 80 mg daily.
- Primary endpoint: objective response rate (ORR). Secondary endpoints: 6-month progression-free survival (PFS), overall survival, and toxicity.
Main Results:
- 13 patients were evaluable for efficacy; median age 63, 62% ECOG PS 1, 31% received >3 prior therapies. Brain cancers comprised 54% of cases.
- Objective response rate (ORR) was 15.4% (2/13), with 6-month progression-free survival (PFS) at 16.7%.
- Responses observed in neuroendocrine carcinoma (EGFR exon 20 S768T, exon 18 G719C) and epithelial carcinoma (EGFR D770_N771insSVD). Common adverse events: diarrhea, thrombocytopenia, maculopapular rash.
Conclusions:
- Osimertinib did not meet the primary efficacy endpoint in this pretreated cohort with diverse advanced cancers and EGFR mutations.
- Responses in specific rare EGFR mutations (S768T, G719C, D770_N771insSVD) suggest potential in certain tumor types.
- Osimertinib demonstrated a well-tolerated safety profile consistent with prior studies.
More Related Videos
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
09:38Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
