- Adjuvant chemotherapy is recommended in patients with resected stages II to IIIA (and select IB) NSCLC; however, recurrence rates are high. In the phase 3 ADAURA study (NCT02511106), osimertinib was found to have a clinically meaningful improvement in disease-free survival (DFS) in patients with resected stages IB to IIIA EGFR-mutated (EGFRm) NSCLC. Here, we report prespecified and exploratory analyses of adjuvant chemotherapy use and outcomes from ADAURA.
- In 2018, durvalumab was approved by the U.S. Food and Drug Administration as consolidation immunotherapy for patients with stage III NSCLC after definitive chemoradiotherapy (CRT). However, whether durvalumab benefits patients with EGFR-mutated NSCLC remains unknown.
- EGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).
- The survival of patients with EGFR mutation-positive lung cancer has dramatically improved since the introduction of EGFR tyrosine kinase inhibitors (EGFR-TKIs). Recently, osimertinib showed significantly prolonged progression-free survival than first-generation EGFR-TKI in first-line treatment, suggesting that a paradigm change that would move osimetinib to first-line treatment is indicated. We performed N-ethyl-N-nitrosourea (ENU) mutagenesis screening to uncover the resistant mechanism in first- and second-line osimertinib treatment.
- Osimertinib, a third-generation EGFR tyrosine kinase inhibitor has demonstrated efficacy in tumors harboring the EGFR T790M resistance mutation. Inevitably, resistance to third-generation inhibitors results in disease progression, with the EGFR C797S mutation being one of several resistance pathways identified to date. On the basis of preclinical data, we report what is the first known case of a patient harboring the T790M and C797S mutations in trans treated with combination gefitinib and osimertinib.
- The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as EGFR C797S. In vitro study proved that cells harboring EGFR C797S in trans with T790M are sensitive to a combination of first- and third-generation EGFR tyrosine kinase inhibitors. However, this has not been reported clinically.
- Osimertinib is an EGFR inhibitor licensed for the treatment of EGFR-mutant, T790M-positive NSCLC. Previously unreported, frequent transient asymptomatic pulmonary opacities were noted in patients during osimertinib therapy at the University of Colorado.