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J.S. Yun
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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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P2.03-024 - Phase II Trial of AZD9291 in Second-Line Treatment after Acquired Resistance with T790M Mutation Detected From Circulating Tumor DNA (ID 8736)
09:30 - 09:30 | Author(s): J.S. Yun
- Abstract
Background:
Administering the best treatment after acquiring resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) requires the knowledge of the resistance status. In this trial, the treatment efficacy of osimertinib (AZD9291) was assessed in patients with non-small-cell lung carcinoma (NSCLC) harboring T790M resistance mutation, which was detected in the circulating tumor DNA (CtDNA) without re-biopsy of the tumor tissue.
Method:
To prove 60% response rate of osimertinib compared to 30% as null hypothesis, and considering 10% drop out rate, 19 subjects were recruited. To extract CtDNA, 15 mL of peripheral blood was withdrawn and centrifuged immediately before storage. Cobas® v2 RUO (Roche diagnostics) and PANA mutyper® (Pangene, Korea) were used to detect the EGFR mutations from CtDNA. Osimertinib was prescribed as an 80 mg tablet once in a day irrespective of the food intake.
Result:
Eighty patients with acquired resistance to prior EGFR TKIs were screened for T790M resistance mutation, and the CtDNA of 21 subjects (26.3%) showed T790M mutation. T790M mutation was detected by both PANA mutyper® and Cobas® in 13 cases, T790M was detected only by PANA mutyper® in 4 cases, and only by Cobas® in 4 cases. Nineteen subjects (age: 64.4 ± 11.6 years old, 14 women, 5 men) were enrolled in this prospective single arm trial from September 2016 to April 2017. Prior EGFR TKIs were afatinib (n=3), erlotinib (n=4), gefitinib (n=10), erlotinib and afatinib (n=1), and gefitinib and afatinib (n=1). Twelve subjects had exon 19 deletion of EGFR gene, 4 had L858R point mutation, one showed exon 19 deletion and L858R, 1 had G719X, and 1 case showed no activating mutation. The response to osimertinib was evaluable in 15 subjects; 4 subjects dropped out from this trial before response evaluation. Among the 15 subjects (efficacy analysis set), partial remission was observed in 10 cases (66.7%).
Conclusion:
Assuming 40% of screened patients are harboring T790M mutation, sensitivity of CtDNA testing is 65% using both tests, and 53% with either test. Toxicity and survival analyses will be followed. (ClinicalTrials.gov Identifier: NCT02769286)
