Phase II study of osimertinib in patients with epidermal growth factor receptor mutations: Results from the NCI-MATCH ECOG-ACRIN (EAY131) trial subprotocol E Journal Article
| Authors: | Chen, M. F.; Song, Z.; Yu, H. A.; Sequist, L. V.; Lovly, C. M.; Mitchell, E. P.; Moscow, J. A.; Gray, R. J.; Wang, V.; McShane, L. M.; Rubinstein, L. V.; Patton, D. R.; Williams, P. M.; Hamilton, S. R.; Umemura, Y.; Tricoli, J. V.; Conley, B. A.; Arteaga, C. L.; Harris, L. N.; O'Dwyer, P. J.; Chen, A. P.; Flaherty, K. T. |
| Article Title: | Phase II study of osimertinib in patients with epidermal growth factor receptor mutations: Results from the NCI-MATCH ECOG-ACRIN (EAY131) trial subprotocol E |
| Abstract: | PURPOSEThe 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.METHODSEligible 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.RESULTSA 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.CONCLUSIONIn 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. © 2024 by American Society of Clinical Oncology. |
| Keywords: | adult; cancer survival; clinical article; human tissue; treatment response; aged; survival rate; gene mutation; overall survival; exon; drug tolerability; fatigue; erlotinib; diarrhea; drug efficacy; drug safety; side effect; systemic therapy; cancer patient; glioma; cancer grading; anorexia; progression free survival; multiple cycle treatment; ovary cancer; phase 2 clinical trial; anemia; leukopenia; nausea; thrombocytopenia; qt prolongation; epidermal growth factor receptor; cohort analysis; pruritus; hyponatremia; maculopapular rash; lung adenocarcinoma; glioblastoma; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; carcinoma; telomerase reverse transcriptase; brain cancer; adenosquamous carcinoma; gastroesophageal reflux; dry skin; astrocytoma; neuroendocrine carcinoma; paranasal sinus carcinoma; body weight loss; response evaluation criteria in solid tumors; afatinib; human; male; female; article; osimertinib; ecog performance status |
| Journal Title: | JCO Precision Oncology |
| Volume: | 8 |
| ISSN: | 2473-4284 |
| Publisher: | American Society of Clinical Oncology |
| Date Published: | 2024-01-01 |
| Start Page: | e2300454 |
| Language: | English |
| DOI: | 10.1200/po.23.00454 |
| PUBMED: | 38591867 |
| PROVIDER: | scopus |
| PMCID: | PMC10896470 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed; MSK corresponding author is Helena Yu -- Source: Scopus |
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