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R. Fritz
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-025 - Prevalence of EGFR T790M Mutation in NSCLC Patients after Afatinib Failure, and Subsequent Response to Osimertinib (ID 8797)
09:30 - 09:30 | Author(s): R. Fritz
- Abstract
Background:
In patients with EGFR-mutant non-small-cell lung cancer (NSCLC), progression inevitably occurs after 9 to 14 months of treatment with EGFR tyrosine kinase inhibitors (TKIs). EGFR T790M mutations have been identified as the most common mechanism of acquired resistance. Analyses assessing the frequency of acquired T790M mutations have mainly been conducted in patients receiving the first-generation EGFR TKIs erlotinib and gefitinib, however limited data is available on the prevalence of this mutation after failure of the ErbB family blocker afatinib. This retrospective analysis aimed at determining the prevalence of EGFR T790M mutation in patients who had benefitted from afatinib therapy, but ultimately developed progression. Another objective was the assessment of response to the subsequent treatment with the third-generation EGFR TKI osimertinib, which is the treatment of choice for patients who have developed T790M mutations.
Method:
The analysis included consecutive patients with stage IV adenocarcinoma of the lung and sensitizing EGFR mutations who had progressed on first-, second- or third-line afatinib treatment after experiencing at least 3 months of disease stabilization. Mutation status was assessed using liquid biopsy or both liquid biopsy and tissue re-biopsy. Patients with confirmed T790M mutation received osimertinib.
Result:
T790M mutations were found in 27 of 48 patients, corresponding to a prevalence rate of 56.3%. The concordance rate between liquid biopsy and re-biopsy was 80%. In the total cohort, the objective response rate (ORR) obtained with afatinib was 89.6%, and in the patients who developed T790M mutation, 92.6%. Complete responses (CR) occurred in 25.0% and 37.0%, respectively, and partial responses (PR) in 64.6% and 55.6%, respectively. In the patients who received osimertinib after the discovery of T790M mutations, ORR was 81.5%, with CR and PR rates of 22.2% and 59.3%, respectively.
Conclusion:
The prevalence of acquired T790M mutations as assessed in this cohort was consistent with the mutation rates reported for patients who progressed on first-generation EGFR TKI treatment. T790M mutation appears to be the main mechanisms of acquired resistance to afatinib. The development of this mutation was not affected by any baseline characteristics. These real-world data confirm that for patients with advanced, EGFR-positive NSCLC who progressed on afatinib and developed T790M mutations, osimertinib therapy elicited excellent response rates, with a substantial proportion of patients achieving complete remissions.
