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D.B. Ong
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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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P3.01-088h - Resistance Mechanisms Causing First-line Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Treatment Failure (ID 9990)
09:30 - 09:30 | Author(s): D.B. Ong
- Abstract
Background:
Patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer receiving first-line EGFR-tyrosine kinase inhibitor (TKI) inevitably developed disease progression after 9-13 months.
Method:
Before 1[st] January 2017, patients were investigated for resistance mechanisms upon failure of first-line EGFR-TKI by tissue re-biopsy. Liquid biopsy to detect secondary T790M mutation in plasma cell free tumor-DNA (cfDNA) was only performed if tissue re-biopsy was not feasible. Starting 2017, liquid biopsy was the first-choice of investigation. Tumor re-biopsy was only perfomed when cfDNA was negative for T790M mutation or if the patients had rapidly enlarging tumors.
Result:
Of 45 patients who were tested, 31(68.9%) underwent tissue re-biopsy and 14 (31.1%) underwent liquid biopsy as the first investigation to determine the presence of T790M mutation. For the latter group, 4 (8.9%) patients subsequently also had tumor re-biopsy. T790M mutation was detected in 30 (66.7%) of the 45 patients. C-Met amplification was tested in 7 T790M mutation-negative patients for possible recruitment into a clinical trial with 4 of them showing c-Met amplification. Small cell lung cancer transformation and ALK rearrangement were detected in 2 (5.7%) and in 1 (2.9%) of the re-biopsy tissue specimens, respectively. The resistance mechanisms in 8 patients (17.8%) was unknown. In short, two-third (66.7%) of our patients had T790M mutation upon first-line EGFR-TKI failure; while another one-third (33.3%) failed first-line EGFR-TKI due to other resistance mechanisms. The demographic, clinical and treatment characteristics were equally distributed among these 2 groups of patients. (Table 1)Table 1. Demographic, clinical and treatment characteristics of 45 patients with first-line EGFR-TKI treatment failure
Characteristic Total patients (n = 45) T790M mutation (n = 30) Other resistance mechanims (n =15) p value of univariate analysis Gender, No (%). Male Female 18 (40.0) 27 (60.0) 13 (43.3) 17 (56.7) 5 (33.3) 10 (66.7) 0.780 Smoking history, No (%). Never Ex or current smoker 36 (80.0%) 9 (20.0%) 22 (73.3) 8 (26.7) 14(93..3) 1 (6.7) 0.963 EGFR mutation subtype, No (%) Exon 19 deletion Exon 21 L858R Others Unknown 26 (57.8) 16(35.6) 2 (4.4) 1(2.2) 17 (56.7) 12 (40.0) 1 (3.3) 0 9 (60.0) 4 (26.7) 1 (6.7) 1 (6.7) 0.999 Treatment received, No (%) EGFR-TKI EGFR-TKI followed by chemotherapy 34 (75.5) 11 (24.5) 22 (73.3) 8 (26.7) 12 (80.0) 3 (20.0) 0.484 Best tumor response, No (%) Partial response Stable disease Disease progression 38 (84.4) 6 (13.3) 1 (2.2) 27 (90.0) 2 (6.7) 1 (3.3) 11 (73.3) 4 (26.7) 0 0.419 Initial progression free survival, months Median 13.0 13.0 11.7 0.538
Conclusion:
T790M mutation is the commonest acquired resistance mechanism causing first-line EGFR-TKI treatment failure. There was no difference in the clinical and treatment characteristics between patients with and without acquired T790M mutation as causes of resistance to first-line EGFR-TKI treatment.
