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H. Astudillo
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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): H. Astudillo
- 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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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-020 - ALK Rearrangements Epidemiology in Latin America (CLICaP) (ID 2957)
09:30 - 09:30 | Author(s): H. Astudillo
- Abstract
Background:
Latin American countries are heterogeneous in terms of lung cancer incidence, ethnicity, and exposure to potential carcinogens. The discovery of the echinoderm microtubule-associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) translocation as an oncogenic driver has led to the development of novel therapies with activity in vitro and in the clinic. In this study we evaluated the frequency and clinical characteristics of ALK rearrangements in six Latin-American countries.
Methods:
A total of 2799 biopsies of advanced NSCLC patients from 6 countries of Latin America (Argentina, Colombia, Costa Rica, Panama, Ecuador, and Mexico) were evaluated by the method fluorescence in situ hybridization (FISH) for detection of ALK-rearrangements. Demographic and clinicopathologic characteristics were analyzed.
Results:
The FISH analyses showed positive ALK fusion gene status in 6.55% (181/2761) of the total sample from all participating countries. ALK+ for each country was a follows: Argentina 6.08% (105/1726), Colombia 4.83% (10/207), Costa Rica 4.83% (2/49), Mexico 8.57% (64/746), and Panama 0% (0/33). Ecuador only used immunohistochemistry for ALK detection rearrangement; therefore, these samples were excluded from FISH technique analysis.
Conclusion:
The frequency of ALK rearrangement in Latin America is higher than previously reported for the Caucasian and Japanese populations. In addition, there is significant continental variability. Until now, FISH for ALK testing is not widely available in Latin America due to its high cost, time-consumption and result interpretation. There is an increased need to develop a common platform for genomic evaluation in developing countries.
