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Luis Cabrera-Miranda
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EP1.12 - Small Cell Lung Cancer/NET (ID 202)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.12-16 - CD47 Expression and Prognosis in Patients with Small Cell Lung CancerCD47 Expression and Prognosis in Patients with Small Cell Lung Cancer (ID 2935)
08:00 - 18:00 | Author(s): Luis Cabrera-Miranda
- Abstract
Background
CD47 is an integral membrane protein expressed in all cells. CD47 present two opposing roles in cell survival. CD47 can interact with signal-regulatory protein-α (SIRP-a) on macrophages, prevents phagocytic clearance. Besides, CD47 signaling through the thrombospondin-1 limits self-renewal and suppresses expression of the stem cell transcription factors cMyc, Sox2, Oct4, and Klf4 in non-transformed cells. Data on the clinical significance of CD47 expression in patients with small cell lung cancer remain limited.
Method
Forty-five naive patients with small cell lung cancer diagnosis were evaluated. Tumor samples obtained by biopsy or surgical resection, were collected for CD47 evaluation. Tumor samples were scored according to the fraction of stained cells at each intensity. The staining intensity of the cell membrane was scored within a scale ranging from 0-3. To determine the prognostic and predictive biomarkers of CD47, patients were stratified according to a cutoff point. This cutoff was optimized as a function of overall survival (OS) using the X-tile and Cutoff Finder software
Result
Preliminary results showed that CD47 was present in 26.7% of population. We stratified the CD47 in two cohorts: CD47 positive-negative and a score of CD47>80. The CD47>80 was present mainly in patient with more than 60 years old (35% vs. 8.0%, p=0.024). Longer overall survival was associated with ECOG-PS 0-1 (20.2 vs. 6.9 p=0.001), disease stage IIIB (49.4 vs. 8.0, p=0.020), absent of CNS metastases (14.1-6.8, p=0.016) and absent of pleural effusion (16.2 vs. 6.99, p=0.002). Interestingly, patient with CD47 positive present better OS (10.8 vs. 6.99, p=0.485) but not reaching significance and patient with a score of CD47>80 have better OS (14.0 vs 9.2, p=0.296).
Conclusion
Immune checkpoint CD47 expressed on the surface of tumor cells allows them to escape immunosurveillance. We previously reported that high CD47 expression was associated with the presence of somatic EGFR mutations in patients with NSCLC. In these patients, high CD47 expression was an independent prognostic factor of worse progression-free survival. Recent studies have indicated that the signal-regulatory protein (SIRP)α–CD47 pathway regulate a phagocytosis checkpoint in macrophages and other innate immune cells. In contrast, in this report we found that high CD47 expression was associated with <60 years old patient and better overall survival. Previously, studies in small cells lug cancer express high levels of CD47 and the blocking of CD47 enhances phagocytosis inhibits tumor growth. CD47 have a dual role, when interact with SIRPα avoid clearance of cells, but it interacts with thrombospondin 1 inhibits cell cycle progression and induces senescence in endothelial cells. Previous studies have shown that the protein TSP1 is as potent inhibitor of angiogenesis and its antiangiogenic activity is mediated by its receptors, CD36 and CD47. In conclusion CD47 have different function according to the ligand, and is a potential biomarker in cancer
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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
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-40 - Normalization of Carcinoembryonic Antigen Levels Is Associated with Survival Improvement in Patients with Advanced Non-Small Cell Lung Cancer (Now Available) (ID 2611)
10:15 - 18:15 | Author(s): Luis Cabrera-Miranda
- Abstract
Background
Serum carcinoembryonic antigen (CEA) levels are elevated in approximately 65% of the Non-small cell lung cancer (NSCLC) patients with adenocarcinoma histology. Elevated CEA levels are an independent prognostic factor for overall survival (OS) in early and advanced NSCLC stages. Previous reports from our group suggest that the decrease or increase in CEA serum levels is strongly associated with response and progression to systemic treatment. However, determination of CEA levels is not included in standard guidelines, such as National Comprehensive Cancer Network (NCNN). The aim of this study is to analyze the progression-free survival (PFS) and overall survival (OS) in NSCLC patients with elevated CEA levels at diagnosis and its association with systemic treatment response.
Method
We performed a retrospective analysis of patients with advanced NSCLC with an elevated serum level baseline of CEA (>20 ng/ml) that received treatment according to international guidelines. The serum CEA levels were measured every two cycles of platinum-based chemotherapy or a tyrosine kinase inhibitor (TKI) treatment. The change in serum CEA levels in response to treatment and the association with overall survival and progression free survival was evaluated.
Result
Between March 2004 and February 2018, 748 patients with diagnosis of advanced NSCLC and CEA levels >20 ng/mL were included in the analysis. Median age was 60.2 years old, 631 patients (84.4%) had adenocarcinoma histology. From 338 patients evaluated for EGFR mutations, 139 (31.3%) harbored an EGFR mutation. The median OS was 23.3 months (95% CI 19.4-26.9) in patients who completely normalized CEA vs 10.0 months (95% CI 8.9-11.2) in patients who did not achieved CEA normalization, with a HR 0.48 95% CI (0.35 -0.67) p <0.0001. The median OS was 15.5 months (95% CI 13.4-17.6) in patients who showed a decrease in CEA levels vs 8.8 months (95% CI 7.5-10.1) in those who did not. Reduction in CEA levels was associated with better OS, either in patients treated with TKI or platinum-based chemotherapy.
Conclusion
The normalization or decrease of the serum CEA levels is a biological marker that serves as tool associated with OS. Based on these findings and previous reports, CEA determination should be included in the clinical guidelines for NSCLC as response biomarker. Serum CEA levels should be part of the standard follow-up of NSCLC patients.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-43 - Cost-Effectiveness of 1st-Line Treatment EGFR-TKIs for Advanced NSCLC Patients Harboring EGFR Mutation in Mexico (Now Available) (ID 1146)
10:15 - 18:15 | Author(s): Luis Cabrera-Miranda
- Abstract
Background
As cancer care costs are rising at an unprecedented rate, it is crucial to provide evidence-based justification for promising but expensive therapeutic approaches such as Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). EGFR-TKIs such as gefitinib, erlotinib and afatinib had become the standard first-line treatment for EGFR gene mutation-positive non-small cell lung cancer (NSCLC) improving progression-free survival (PFS) and overall survival (OS) of these patients. However, the economic impact of them remain unclear. Hence, we aimed to assess healthcare costs during and after progression to treatment and to compare the cost-effectivess and safety of the 1st-line treatment with EGFR-TKIs in patients with advanced non-small cell lung cancer (NSCLC) in Mexico.
Method
The health and economic outcomes of three first-line strategies (gefitinib, erlotinib, and afatinib) among NSCLC patients harboring EGFRmutations were estimated and assessed. Costs in the Mexican setting were obtained from local hospital data and public national purchasing sources. The structure used in this analysis was a Markov model with three possible health states: free of progression, progression and death considering a time horizon of 3 and 5 years. The probabilities of transition and the use of resources used to feed the model were retrospectively collected by reviewing medical records of patients who were treated at the Instituto Nacional de Cancerologia (INCan) of Mexico between April 2013 and June 2017. Probabilistic sensitivity analysis (PSA) was conducted with a Monte Carlo simulation.
Result
Similar hazards of progression and death were obtained when constrasting afatinib vs. erlotinib, [HR:0.91 (95% CI: 0.59 -2.07) and 0.82 (95% CI: 0.56-2.65), respectively] as well as when contrasting the hazards of progression and death of afatinib vs. gefininib [HR:0.87 (95% CI: 0.87-1.53) and 0.94 (95% CI: 0.74-1.55), respectively]. However, statistically significant differences were identified between the costs of the treatment both the total cost (p<.001) and the daily cost (p <0.001) of treatment. The most expensive treatment was with afatinib, followed by erlotinib and gefitinib. In addition, treatment with afatinib showed the highest cost associated with adverse events. PSA with Monte Carlo simulations showed robustness of estimations.
Conclusion
Although equivalent effectiveness and safety of the three arms of the study was found, substantial differences in treatment costs were observed. Nonetheless, we should highlight that patient selection is absolutely critical for cost-efectiveness analyses; as well as longer follow-up of existing data could substantially alter the conclusions of this analysis.
