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O. Burghuber
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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): O. Burghuber
- 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.
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P3.03 - Chemotherapy/Targeted Therapy (ID 719)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.03-024 - Real-Life Experience and Clinical Characterization of BRAF V600E Mutation in Austrian NSCLC Patients (ID 10113)
09:30 - 09:30 | Author(s): O. Burghuber
- Abstract
Background:
Targeted therapy is becoming increasingly important and has improved the overall survival for patients with NSCLC. BRAF[V600E] mutations (Val600Glu) are observed in 1-2% of lung cancer and play a major role in targeted therapy by providing an opportunity for affected patients as possible allocable target. In Austria an effective therapy is available with Dabrafenib and Trametinib. The aim of this retrospective analysis was to support ongoing research on the frequency of this promising genetic alteration by determining the prevalence of BRAF[V600E] mutations among Austrian NSCLC patients. We also examined clinical characteristics of these patients.
Method:
Patient characteristics including age, sex, race, smoking history and localization of biopsy were collected. Tumor tissue from bronchoscopy, CT- and ultrasound guided biopsies as well as surgical specimen with histological type of adenocarcinoma and NSCLC NOS (Not Otherwise Specified) excluding large cell carcinoma and neuroendocrine carcinoma was reflex tested independent of the tumor stage and clinical characteristics (like sex, smoking history, demography) for BRAF mutations. The BRAF mutation detection was performed since February 2017 with the BRAF/NRAS Mutation Test Kit from Roche on a COBAS[®] z 4800 Analyzer.
Result:
BRAF alterations were found in 11 of 118 tested patients (9.3%), of which 7 patients (5.9 %) showed a BRAF[V600E] positive mutation. Out of these patients with BRAF[V600E] positive mutation, 4 were women and 3 men. 3 patients were Never-Smoker, 2 were former smokers and 2 smokers. Biopsies in 5 patients were taken from the primary tumor, in 1 patient from the lymph nodes and in 1 patient the analysis was performed by drainage of pleura effusions. Median age was 69 years. All patients were Caucasian.
Conclusion:
The prevalence of BRAF[V600E] mutation in this real-world data, assessed in a cohort of 118 people, was higher than BRAF[V600E] mutation rates previously reported by other published data, and thus underline the importance of reflex testing for this druggable target independent of clinical characteristics.
