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Chongrui Xu
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-85 - Treatment for Advanced NSCLC with EGFR Mutations and De Novo MET Amplification/Overexpression (ID 2190)
09:45 - 18:00 | Author(s): Chongrui Xu
- Abstract
Background
Combination of epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) tyrosine kinase inhibitors (TKIs) are effective in advanced non-small-cell lung cancer (NSCLC) patients harboring EGFR mutation and acquired MET-amplification. However, there are few reports about treatments of patients with EGFR mutation and de novo MET amplification/ overexpression.
Method
We retrospectively screened 88 consecutive advanced NSCLC patients harboring EGFR mutation and de novo MET amplification/overexpression at Guangdong Provincial People's Hospital of China from January, 2014 to December, 2018. Among them, a total of 41 patients receiving first-line targeted therapy were included and stratified into EGFR-driven, MET-driven and EGFR/MET co-driven groups illustrated respectively in Table 1.
Table 1. Classification of advanced NSCLC with EGFR mutation and MET overexpression/amplification. Group EGFR mutation MET overexpression/amplification Response to first-line TKI EGFR-driven Exon 19 deletion or exon 21 L858R mutation (tested by next generation sequencing (NGS) or amplification refractory mutation system (ARMS) or polymerase chain reaction (PCR)). Overexpression: strong intensity staining was in more than 50% of tumor cells (tested by immunohistochemistry (IHC)).
Amplification: CNG≥5, or MET/centromeric portion of chormosome 7 ratio≥2.2, with an additional criterion of focal amplification was in more than 10% of tumor cells (tested by fluorescence in situ hybridization (FISH)).
PFS＞3 months, best response is complete response (CR)/partial response (PR)/stable disease (SD); not receiving MET-TKIs in later-line treatment, or had MET-TKIs but PFS≤3 months. MET-driven PFS≤3 months, receive MET-TKIs monotherapy or MET-TKIs plus EGFR-TKIs in later-line treatment and PFS＞3months, or PFS≤3 months，but with acquired mechanism to MET. EGFR/MET co-driven Response to EGFR-TKIs at least one time, receiving EGFR-TKIs plus MET-TKIs in later-line treatment and PFS＞3 months, or PFS≤3 months, but with acquired mechanism to MET.
Result
Among enrolled patients, 40 of them received first-line first-generation EGFR-TKIs while 1 treated with MET-TKI. Twenty-eight received targeted therapy in the later-line treatments after resistance. Thirty-one (75.6%), 5 (12.2%) and 5 (12.2%) patients were classified into EGFR-driven, MET-driven and EGFR/MET co-driven groups. Median progression-free survival (PFS) was 12.1, 1.0 and 5.3 months respectively in the first-line setting. Objective response rates were 58.1%, 0.0% and 20.0% (P=0.028) respectively. Among 28 patients receiving subsequent targeted therapies, 58.1% (18/31), 100.0% (5/5) and 100.0% (5/5) were EGFR-driven, MET-driven and EGFR/MET co-driven respectively. Median PFS was 7.0, 6.5 and 10.3 months for the EGFR-driven group receiving subsequent EGFR-TKIs, the MET-driven group receiving MET-TKIs with or without EGFR-TKIs, and the EGFR/MET co-driven group treating with EGFR-TKIs plus MET-TKIs respectively (P=0.399). Also, no significant difference was observed in overall survival for these 28 patients (33.8 vs. 11.8 vs. 27.9 months, P=0.098).
Conclusion
Subsequent individualized targeted therapy or co-targeted therapies might favor clinical outcomes for both MET-driven and EGFR/MET co-driven patients with advanced NSCLC after resistance to first-line EGFR-TKIs.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-80 - Clinical Outcomes in Advanced EGFR-Mutant NSCLC Patients Treated with First-Generation EGFR TKIs Followed by Subsequent Osimertinib (ID 1732)
10:15 - 18:15 | Author(s): Chongrui Xu
- Abstract
Background
Treatment with first-line epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) plus subsequent osimertinib is standard of care for advanced (EGFR)-mutant non-small cell lung cancer (NSCLC) harboring T790M mutation. However, few data are available that have assessed the cumulative survival benefit of sequential EGFR TKIs in patients with EGFR-mutant NSCLC with T790M mutations in ‘real-world’ clinical practice.
Method
We retrospectively identified advanced EGFR-mutant NSCLC patients treated with first-line EGFR TKIs plus subsequent osimertinib between January 27th, 2015 and December 1st, 2018 at our institute. Clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). The primary endpoint was overall survival (OS) calculated from first-line treatment start to death or the last follow-up, and the secondary endpoint was progression-free survival (PFS) with osimertinib defined as the time from the first dose of osimertinib to disease progression or death. Primary resistance to osimertinib was defined as PFS≤4 months for T790M-mutant patients treated with osimertinib. The last follow-up time was January 27th, 2019. Median follow-up time was 52.0 months (range, 9.0~108.0 months).
Result
Among 117 eligible patients treated with first-line EGFR TKIs plus subsequent osimertinib, 96 had T790M mutation and 21 showed negative T790M mutation or unknown status at the baseline of osimertinib treatment,. Median OS was significantly prolonged in T790M-mutant patients than those with negative/unknown T790M mutation (58.0 vs. 28.3 months, p＜0.001). However, there was no significant difference in median PFS with osimertinib between the two groups. Furthermore, there was no significant difference in both median OS and PFS with osimertinib between the non-brain metastatic and brain metastatic groups (median OS, 58.0 vs. 54.8 months, p=0.840; median PFS, 11.8 vs. 9.1 months, p=0.145). Median OS was significantly shortened in patients (N=20) with primary resistance to osimertinib than those (N=72) with PFS＞4 months (38.2 vs 54.8 months, p=0.027).
Conclusion
In real-world clinical practice, treatment with first-generation EGFR TKIs plus subsequent osimertinib for T790M-mutant patients can significantly prolong OS than those with negative/unknown T790M mutation. However, survivals are similar between the patients with and without brain metastases at the baseline of osimertinib. OS is significantly shorter in those with primary resistance to osimertinib.
Non-brain metastasis at the baseline
(n=55)
Brain metastasis at the baseline
(n=41)
P-value
Osimertinib PFS≤4m
(n=20)
Osimertinib PFS＞4m
(n=72)
P-value
Sex
Male
21 (38.2%)
20 (48.8%)
0.299
7 (35.0%)
32 (44.4%)
0.450
Femal
Age,years
≤55
＞55
34 (61.8%)
19(34.5%)
36(65.5%)
21 (51.2%)
18(43.9%)
23(56.1%)
0.357
13 (65.0%)
9 (45.0%)
11(55.0%)
40 (55.6%)
27(37.5%)
45(62.5%)
0.543
ECOG PS
0-1
54(98,2%)
38(92.7%)
0.000
20(100%)
68(94.4%)
0.281
2-4
1(1.8%)
3(7.3%)
0(0%)
4(5.6%)
Histology
adenocarcinoma
53 (96.4%)
41 (100%)
0.217
18 (90.0%)
72 (100%)
0.007
non-adenocarcinoma
2 (3.6%)
0 (0%)
2 (10.0%)
0 (0%)
