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J. Negueb
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MINI 16 - EGFR Mutant Lung Cancer 2 (ID 130)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:G.J. Riely, M.C. Garassino
- Coordinates: 9/08/2015, 16:45 - 18:15, Four Seasons Ballroom F3+F4
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MINI16.11 - Plasma HGF Reduction Is Associated with Better Prognosis in EGFR-Positive Advanced Lung Adenocarcinoma Patients Treated with Afatinib (ID 1729)
17:45 - 17:50 | Author(s): J. Negueb
- Abstract
- Presentation
Background:
Afatinib, an irreversible tyrosine kinase inhibitor (TKI), has shown clinical benefits and prolonged progression free survival in EGFR mutated patients. HGF, a ligand of c-MET, may be involved in resistance to EGFR-TKIs.
Methods:
A total of 66 patients with advanced lung adenocarcinoma (stage IIB and IV) and documented progression to first-line chemotherapy were enrolled to receive afatinib 40 mg/day. Mutational EGFR and HER-2 status were assessed by RT-PCR. HER2 amplification was evaluated by FISH. Plasma HGF levels were measured by ELISA before and 2 months after the start of treatment with afatinib. We assessed the change in plasma HGF levels and the association with objective response rate (ORR), progression free survival (PFS) and overall survival (OS). The protocol is registered in ClinicalTrials.gov (NCT01542437).
Results:
We identified 2 patients carrying a HER2 mutation and both presented stable disease (SD). HER2 amplification was not detected. HGF-positive plasma reduction status had a significant higher ORR (75.0% vs 44.1% p= 0.011), and was strongly associated with longer PFS (HR 0.40 [95% CI 0.18 - 0.87], p= 0.02) and OS (HR 0.31 [0.13 - 0.71] p=0.006). A stratified multivariate analysis in EGFR mutated patients showed that the HGF plasma levels reduction remains as a significant and independent factor associated with longer PFS (HR 0.34 [95% CI 0.13 - 0.89] p= 0.04) and OS (HR 0.34 [95% CI 0.13 - 0.88] p= 0.02).
Conclusion:
HGF plasma levels reduction is strongly related to better outcomes with afatinib therapy, irrespective of EGFR mutation status. The lack of reduction might allow the identification of a subgroup of patients who will not expected to respond and could benefit with the use of drugs targeting the HGF-c-Met axis. Further studies are warranted.
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P3.06 - Poster Session/ Screening and Early Detection (ID 220)
- Event: WCLC 2015
- Type: Poster
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.06-026 - Gene Expression Signature to Predict Early Development of Brain Metastasis in Lung Adenocarcinoma (ID 1273)
09:30 - 09:30 | Author(s): J. Negueb
- Abstract
Background:
Advances in systemic treatment have substantially improved the overall survival of advanced lung adenocarcinoma patients, and risk of brain metastases(BM) is higher. The survival of patients with symptomatic BM is poor. The identification of NSCLC patients with a high risk of developing BM would enable pre-emptive intervention to improve the outcome.
Methods:
A total of 53 biopsies of primary lung tumor adenocarcinoma stage IV treatment-naïve were analyzed for gene expression profiling using Affymetrix HuGene 1.0 ST and were processed in R using Bioconductor libraries. All patients were evaluated with brain MRI at diagnosis with a 3-month follow-up for BM development. Patients were classified into two groups: early-BM( < 6 months) and late-BM( > 6 months). A second independent cohort of 55 patients was analyzed to validate the gene expression signature (ClinicalTrials.gov: NCT00862173).
Results:
Samples were classified as early-BM(17) and late-BM(6), the remainder 30 never developed BM. Significant changes in gene expression of about100 genes were found. Eleven highly significant genes (B-stat > 12) were associated with process of cell-migrationCNN3(down-reg.) and adhesionCDH10(up-reg); anti-apoptosisBAG1(up-reg); immunological evasionSSX2(up-reg) and RAET1E(up-reg); signaling pathways related to RAS gene RAB9A(up-reg) and RAPGEF5(down-reg); mRNA-tRNA translocationDUS2L(up-reg); methylation controlNOC2L(up-reg); and members of the EGFR family EPGN(up-reg) and IGFR, IGF2BP1(up-reg).
Conclusion:
We describe an 11-gene signature that may predict the risk of BM which has the potential to classify patients and evaluate screening strategies that would facilitate pre-emptive interventional trials such as prophylactic cranial irradiation.
