Study 1 (n=201) showed an ORR of 57% (95% CI: 50%, 64%).
Study 1 (n=201) showed an ORR of 57% (95% CI: 50%, 64%).
Study 2 (n=210) the ORR was 61% (95% CI: 54%, 68%).
The majority (96%) of patients in both trials had ongoing responses at the time of primary analysis and the median DOR had not been reached with duration of ongoing responses ranging from 1.1 to 5.6 months after a median duration of follow-up of 4.2 months (Study 1) and 4.0 months (Study 2). The dose finding phase of Study 1 (n=63) showed an ORR of 51% and median DOR of 12.4 months.
Safety data was evaluated in 411 patients who received osimertinib at a dose of 80 mg daily. The most common adverse events were diarrhea (42%), rash (41%), dry skin (31%), nail toxicity (25%), eye disorders (18%), nausea (17%), decreased appetite (16%), and constipation (15%). The majority of the above adverse events were grade 1-2. The most common Grade 3-4 adverse reactions were pneumonia and pulmonary embolism (2% each).
The most common nonfatal serious adverse events (SAEs) included pneumonia and pulmonary embolus.
The most common nonfatal serious adverse events (SAEs) included pneumonia and pulmonary embolus.
Dose reductions due to adverse events occurred in 4.4% of patients. The most frequent adverse reaction leading to dose reductions or interruptions were prolonged QTc and neutropenia (2% each). Adverse events leading to discontinuation included ILD/pneumonitis (2%), and cerebrovascular accident (1%). Fatal adverse events occurred in 3.2% of patients, including 4 cases of pneumonitis attributed to osimertinib.
The recommended dose and schedule for osimertinib is 80 mg given orally once daily.
The cobas® EGFR Mutation Test v2 (US-IVD), identifies mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissue DNA from non-small cell lung cancer (NSCLC) patients and is intended to be used as an aid in identifying patients with NSCLC for therapy with the EGFR tyrosine kinase inhibitors (TKI) Tarceva® or TAGRISSO™.The test utilizes tissue samples that have been formalin-fixed and paraffin embedded.
The cobas® EGFR Mutation Test v2 (US-IVD), identifies mutations in the epidermal growth factor receptor (EGFR) gene in tumor tissue DNA from non-small cell lung cancer (NSCLC) patients and is intended to be used as an aid in identifying patients with NSCLC for therapy with the EGFR tyrosine kinase inhibitors (TKI) Tarceva® or TAGRISSO™.The test utilizes tissue samples that have been formalin-fixed and paraffin embedded.
The cobas® EGFR Mutation Test v2 identifies 42 mutations in exons 18, 19, 20 and 21 of the EGFR gene using tissue as a sample
The cobas® EGFR Mutation Test v2 US-IVD can be performed in less than 8 hours from isolation to result
Automated result interpretation and test reporting provide consistent, objective and reproducible results from laboratory to laboratory
Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world.
Approximately 1500 patients will be recruited in Europe. The recruitment will be increased beyond that as the study will expand in other regions of the world.
67 patients met the following two eligibility criteria for acquired resistance analysis:
67 patients met the following two eligibility criteria for acquired resistance analysis:
T790M positive on plasma or tumor genotyping at enrollment
Detectable EGFR-TKI-sensitizing mutation in plasma at progression on AZD9291
Of those, 15 (22%) had detectable C797S on ddPCR, all with detectable T790M
C797S was more common with EGFR exon 19 del (13/43, 30%) vs those with L858R (2/24, 8%, p=0.06)
69-year-old female with EGFR-mutant NSCLC metastatic to liver, adrenal, bones who had progression after first-line chemotherapy and subsequent erlotinib
Resistance biopsy was inadequate for genotyping, but plasma genotyping positive for L858R (26%) and T790M (4%)
Initiated AZD9291 and responded on the first scan (-40%) but progressed after 24 weeks
Resistance biopsy undergone for targeted NGS:
Positive for L858R, negative for T790M, positive for MET amplification
MET protein overexpression also seen on IHC
49-year-old male with metastatic NSCLC positive for EGFR exon 19 deletion
49-year-old male with metastatic NSCLC positive for EGFR exon 19 deletion
Developed resistance to first-line erlotinib after 11 months, T790M positive biopsy
Had a confirmed PR to AZD9291 but growth of lung mass, effusion after 5 months
Targeted NGS of progression biopsy shows exon 19 deletion (8% of reads), no T790M, BRAF V600E (6% of reads)
