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L. Ramírez-Tirado
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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)
16:45 - 18:15 | Author(s): L. Ramírez-Tirado
- 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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ORAL 30 - Community Practice (ID 141)
- Event: WCLC 2015
- Type: Oral Session
- Track: Community Practice
- Presentations: 1
- Moderators:P.S.S. Kho, R. Jotte
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 2c-3c
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ORAL30.07 - Different Mutation Profiles and Clinical Characteristics Among Hispanic Patients with NSCLC Could Explain The 'Hispanic Paradox' (ID 748)
16:45 - 18:15 | Author(s): L. Ramírez-Tirado
- Abstract
- Presentation
Background:
Sixteen percent of the U.S. population is Hispanic, predominantly of Mexican ancestry. Recently, two independent American reports demonstrated a higher overall survival (OS) in Hispanic populations compared with non-Hispanic-white populations (NHW) in patients with non-small-cell lung cancer (NSCLC) diagnosis. The latter even when most of the Hispanics are diagnosed at advanced stages of disease and are low-income patients. The aim of our study was to analyze the clinical, pathological, and molecular characteristics as well as the outcomes in a cohort of NSCLC Hispanic patients from the National Cancer Institute of Mexico that could explain this "Hispanic Paradox".
Methods:
A cohort of 1260 consecutive NSCLC patients treated at the National Cancer Institute of Mexico from 2007-2014 was analyzed. Their clinical- pathological characteristics, the mutation-status of EGFR and KRAS and the prognosis were evaluated.
Results:
Patients presented with stages of disease: II (0.6%), IIIa (4.8%), IIIb (18.4%) and IV (76.3%). NSCLC was associated with smoking in 56.5% of the patients (76.7% of male vs. 33.0% of female patients). Wood smoke exposure (WSE) was associated with 37.2% of the cases (27.3% in men vs. 48.8% in women). The frequency of EGFR mutations was 28.1% (18.5% in males vs. 36.9% in females, p<0.001) and the frequency for KRAS mutations was 10.2% (10.3% men vs. 10.1% in women p= 0.939). The median OS for all patients was 23.0 months [CI95% 19.4-26.2], whereas for patients at stage IV, it was 20.1 months [CI 95% 16.5-23.7]. The independent factors associated with the OS were as follows, the ECOG Performance Status, stage of disease, EGFR and KRAS mutation status.
Conclusion:
The high frequency of EGFR mutations and low frequency of KRAS mutations in Hispanic populations and different prevalence in lung cancer-related-developing risk factors compared with Caucasian populations, such as the lower frequency of smoking exposure and higher WSE, particularly in women, might explain the prognosis differences between foreign-born-Hispanics, US-born-Hispanics and NHWs.
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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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P3.04-090 - Association of Nuclear Expression of RAR Beta and YY1 with Prognosis in Advance Non-Small Cell Lung Cancer (ID 1697)
09:30 - 17:00 | Author(s): L. Ramírez-Tirado
- Abstract
Background:
Lung cancer is the most common cause of cancer-related death worldwide and it is responsible for approximately 1.4 million deceases per year. In Mexico, the NSCLC cause more than 6,697 deaths annually. Approximately, 85% of all lung cancer corresponds to NSCLC and unfortunately at diagnosis 60% patients have advanced unresectable disease with a very poor prognosis. The standard of care treatment for advanced disease is platinum-based doublet chemotherapy, this present an objective response rates of 19% to 37% with a 7 to 10 months of median survival. The identification of molecular alteration in NSCLC has transformed the clinical management of this disease, increasing the survival and improves the response in patients. The genetic alterations affect a common group of oncogenic signaling pathways such as retinoid receptors (RR) and yin and yang 1 (YY1) resulting in lung cancer development and progression. The nuclear RR may play a critical role in the process of lung carcinogenesis. In NSCLC, reduction in the levels of mRNA RARβ and RARα have associated with lack of response to treatment and progression. As the same manner, YY1 is a key regulator of multiple signaling pathways involved in differentiation, replication, cellular proliferation and oncogenic transformation. The role of YY1 in development of cancer depend upon the context in which it binds. It could activate a variety of oncoproteins attenuates the stability of the tumor suppressor such as p53 or mediates the activation of genes with tumor-suppressive functions. The aim of this study was to analyze the expression of RARα, RARβ and YY1 and its relationship with overall survival in patients with advanced NSCLC.
Methods:
This was an observational study, where patients with advanced NSCLC at the National Cancer Institute of Mexico City from July 2005 to December 2011 were enrolled. The expression of RARα, RARβ and YY1, was determinate with immunohistochemistry by mean digital pathology and analyzed by Image-Pro Plus.
Results:
Eighty-five patients were included for the analysis. The mean and standard deviation of the nuclei expression of RARα, RARβ and YY1 were (106.7±97), (14±13) and (13±12). Patients with a high RARβ total expression have a better ECOG 0-1 vs 2-3 performance status (92.9 vs 74.4%). Non-smokers had a high nuclei expression of YY1 (61.9 vs <40.5%) and better median OS 15.6 (4.5-26.7 months). Nuclei expression of RAR-β was associated with the nuclei expression of YY-1 (R2 = 0.28; p-Value <0.0001). Also, the higher nuclei expression of RARβ was associated with a higher OS (27.5 vs 8.7 months) in both, the univariate analysis and multivariate analysis (p=0.016; p=0.037).
Conclusion:
The nuclei expression of both RARβ and YY1, could be used as biomarkers to NSCLC prognosis, specifically YY1 predicted a better response in patient that had never smoke.
