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Gang Cheng
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-037 - Understanding Mechanisms of Resistance to Osimertinib by Circulating Tumor DNA Genotyping in Advanced Non-Small-Cell Lung Cancer (ID 9267)
09:30 - 09:30 | Presenting Author(s): Gang Cheng
- Abstract
Background:
Epidermal growth factor receptor (EGFR) T790M mutation is the most common mechanism for resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKI). Osimertinib has been demonstrated to overcome EGFR T790M non-small cell lung cancer (NSCLC). However, most of these patients eventually developed resistance after 10 months. Here we performed a comprehensive next generation sequencing (NGS) using circulating tumor DNA (ctDNA) to study resistance mechanisms in patients with advanced NSCLC who had developed resistance to osimertinib, and to provide potential opportunities for treatment.
Method:
10 advanced NSCLC patients were enrolled in this study after progression from first-generation EGFR-TKI treatment. Patients received osimertinib with 80mg daily, the response rate and progression-free survival (PFS) was assessed during treatment. 10ml peripheral blood was collected from patients after progression from osimertinib, and ctDNA genotyping was performed by next-generation sequence (NGS).
Result:
There were 3 patients received gefitinib and 7 patients received erlotinib before osimertinib therapy. All patients confirmed a partial response (PR) on osimertinib, the median PFS was 13.3 months. The initial gene mutation patterns before osimertinib therapy could be classified into two groups: L858R/Exon 19 Deletion (19Del) +T790M, and L858R/19Del+T790M unknown or wild-type. However, after progression from osimertinib, mutation patterns varied from groups. In the L858R/19Del+T790M group, two of six patients detected with L858R/19Del+T790M+C797S, two patients with L858R (+T790M) +HER2 amplification, and two patients with only 19Del+T790M; In the L858R/19Del+T790M unknown or wild-type group, there was only one patient detected with L858R/19Del+C797S mutation, the other three patients detected with only L858R mutation. For the C797S-mutated patients, it showed that T790M and C797S mutation presented in the same allele (cis) in two patients, while in both trans and cis in one patient. Other EGFR mutations were also detected, such as A750P, L792F, E709K, A1013V, L718V, and EGFR amplification.
Conclusion:
Genotyping of ctDNA in osimertinib resistant patients showed that the resistance might be related to specific gene mutation, e.g., EGFR C797S and HER2 amplification. Our findings provide insight that resistance to osimertinib might be different between T790M-mutated patients and T790M wilt-type patients. Combination therapy of osimertinib with other agents may be candidate to overcome the acquired mutation.
