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H. Lu
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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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P3.03-030 - TP53 Alteration, a Potential Primary Cause of Early Progression in EGFR-Mutated NSCLC Patients Treated with First-Line TKIs (ID 9426)
09:30 - 09:30 | Author(s): H. Lu
- Abstract
Background:
EGFR-TKIs are recommended first-line treatment for patients with EGFR-mutant advanced non-small cell lung cancer (NSCLC). Most patients develop resistance after an average of approximately 12 months. Among various mechanisms, about half are acquired with T790M in EGFR exon 20. Little is known about the mechanisms in patients progressed within 6 months after first-line treatment of EGFR-TKIs. Therefore, we prospectively designed this study to investigate the possible mechanisms of resistance in this group of patients.
Method:
NSCLC patients with sensitive EGFR mutations who treated with first-line EGFR-TKI in Zhejiang Cancer Hospital from Jun 2014 to Jan 2017 were screened prospectively. Tissue samples pre-TKI and after disease progression (RECIST1.1) were collected. Blood samples were collected after disease progression. The study was approved by hospital research ethics committees. Of the total 50 patients enrolled for the study, 21 patients were included and further divided into two groups: patients suffered disease progression within six months after taking EGFR-TKI were classified as Group A (rapid progress group, n=13); patients took EGFR-TKI more than two years were classified as Group B (long term survival group, n=8). Patients with a PFS between 6 months to two years were excluded. We performed NGS of ~416 cancer related genes from the primary cancer samples collected before TKI treatment. Differences of gene alterations between two groups were analyzed.
Result:
The median age was 55 years old (range: 34-75 years). There were 47.6% female and 53.8% non-smokers. All patients in Group A carried TP53 mutation before treatment, none was found in Group B. The average cancer-related genetic mutations is 6.46 (range 3-16, 6 in Group A, 5.6 in Group B, P>0.05). There was enrichment for co-alterations in TP53 (100%), RB1 (38%), NKX2-1 (31%), BIM (30.8%) in pre-treated tissues from Group A. ERCC2 (38%), JAK3 (38%), BRCA2 (25%) were enriched in pre-treated tissues from Group B. Mutation rate of EGFR T790M after resistance was lower in Group A (2/13,15.4%) than in Group B (2/5, 40%). Three patients (3/8) are still benefit from first-line EGFR-TKI without disease progression in Group B. The median PFS was 3 months for Group A (range 1-5 months) and 26.5 months for Group B (range 24-52 months).
Conclusion:
This data highlights a model of genetic collectives as potential mechanisms of rapid progression in first-line EGFR-TKIs treatment. TP53 mutation reduced responsiveness to TKIs and worsen prognosis in EGFR-mutated NSCLC patients, contributing to rapid disease progression. EGFR T790M mutation seems uncommon in rapid progression patients.
