Abstract
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 withmutations. Eligible patients hadmutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer withT790M 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. 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 (exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus (D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash. In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with anexon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with anD770_N771insSVD mutation. Osimertinib was well tolerated and had a safety profile consistent with previous studies.
Overview
- The study 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 mutations. Eligible patients had mutations (T790M or rare activating) and received osimertinib 80 mg once daily. Patients with lung cancer withT790M 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. 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 study aims to evaluate the efficacy and safety of osimertinib in patients with mutations in the epidermal growth factor receptor (EGFR) gene. The primary objective is to determine the objective response rate (ORR) of osimertinib in this patient population. Secondary objectives include 6-month progression-free survival (PFS), overall survival, and toxicity. The study seeks to answer the question of whether osimertinib is an effective treatment option for patients with mutations in the EGFR gene.
Comparative Analysis & Findings
- The study compared the outcomes observed under different experimental conditions or interventions detailed in the study. Specifically, it compared the efficacy and safety of osimertinib in patients with mutations in the EGFR gene to previous studies. The study identified significant differences in the results between these conditions. The ORR of osimertinib in this patient population was 15.4% (n = 2 of 13; 90% CI, 2.8 to 41.0), which is lower than the ORR reported in previous studies of osimertinib in patients with non-small cell lung cancer. The two confirmed RECIST responses were observed in a patient with neuroendocrine carcinoma not otherwise specified (exon 20 S768T and exon 18 G719C mutation) and a patient with low-grade epithelial carcinoma of the paranasal sinus (D770_N771insSVD). The most common (>20%) treatment-related adverse events were diarrhea, thrombocytopenia, and maculopapular rash. In this pretreated cohort, osimertinib did not meet the prespecified end point threshold for efficacy, but responses were seen in a neuroendocrine carcinoma with anexon 20 S768T and exon 18 G719C mutation and an epithelial carcinoma with anD770_N771insSVD mutation. The study suggests that osimertinib may not be as effective in patients with mutations in the EGFR gene as previously thought.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice. The study suggests that osimertinib may not be as effective in patients with mutations in the EGFR gene as previously thought. This has important implications for the treatment of patients with these mutations and highlights the need for further research to identify more effective treatment options. The study also identified two confirmed RECIST responses in patients with neuroendocrine carcinoma not otherwise specified and low-grade epithelial carcinoma of the paranasal sinus. These findings suggest that osimertinib may be effective in some patients with these types of cancers and warrant further investigation. The study also highlights the importance of considering the specific genetic mutations present in a patient when selecting a treatment option. Future research should focus on identifying more effective treatment options for patients with mutations in the EGFR gene and on further exploring the potential of osimertinib in patients with neuroendocrine carcinoma not otherwise specified and low-grade epithelial carcinoma of the paranasal sinus.