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T. Mele
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P1.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 206)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.01-044 - Cost-Effectiveness of Chemotherapy Based on the Tumor Genetic Profile in Elderly Patients with Advanced Non-Small-Cell Lung Cancer (ID 1656)
09:30 - 09:30 | Author(s): T. Mele
- Abstract
Background:
Platinum-Based chemotherapy is still the cornerstone in the treatment of Non-Small Cell Lung Cancer (NSCLC), in non oncogene-addicted patients (pts). Therapeutic algorithm is established on the basis of patient and disease characteristics, such as histology and radiologic features. Pharmagenomic-driven trials are investigating the role of different markers in predicting efficacy and toxicity in NSCLC pts. A better selection of a right therapy for the right patient would improve outcomes ameliorating tolerability and optimize the resources available. The aim of the present study is to carry out a cost-effectiveness analysis, in order to evaluate the economic efficiency of 1st line chemotherapy within a clinical trial (EPIC eudract N 2012-001194-81), in elderly pts affected from advanced NSCLC, looking at efficacy and tolerability.
Methods:
The study population consisted in Elderly Patients Individualized Chemotherapy (EPIC) trial enrolled at San Luigi Hospital (Orbassano-Italy, coordinating centre) from July 2012 to August 2014. Main recruitment criteria: chemotherapy-naïve pts diagnosed with stage IV NSCLC, aged≥70 years, no activating EGFR mutations. We evaluated 48 pts randomised (2:1 ratio) to receive pharmacogenomics-driven chemotherapy assessed according to the genetic profile of primary tumours based on expression of ERCC1, RRM1 and TS evaluated by “Real-Time PCR” (arm A) or standard chemotherapy (arm B). Costs of treatments were calculated using National Health System (NHS) direct costs and 12 months time-horizon. Effectiveness was estimated as Progression Free Survival (PFS). The Incremental Cost-Effectiveness Ratio (ICER) was calculated and pharma-economic analysis was performed setting the Willingness To Pay (WTP) threshold value at 40,000€ per free-disease month gained. The reliability of results was assessed by a probabilistic sensitivity analysis based on “Monte Carlo” method (10,000 simulations) changing the costs and effectiveness variables simultaneously. Number and grade of adverse events were used to determine the tolerability profile.
Results:
The average cost per patient was 10,278.38€ (arm A) and 8,659.53€ (arm B). Related ICER was 4,496.80€ per free-disease month gained and 53,961.73€ per year gained (over the WTP threshold). The scatterplot generated in the sensitivity analysis indicated that higher densities of ICERs, calculated for each simulation, took place at the cross over of the Cartesian axes indicating that there is no clear prevalence of treatment cost-effectiveness. Moreover, the Cost-Effectiveness Acceptability Curve (CEAC) was calculated. This curve demonstrated that treatment A had 35% of probability to be cost-effectiveness.
Conclusion:
This preliminary evaluation, conducted in a subgroup of pts, suggests the relevance of pharmacoeconomic analysis within a clinical trial looking at the best way to identify a tailored treatment in non-oncogene addicted NSCLC pts. Further data will be collected in a larger simple size. Personalised chemotherapy is a potential method addressing both the optimisation of the effectiveness of therapeutic agents and the minimisation of adverse events, objectives even more relevant for elderly and fragile patients, given the possibility to optimize the use of scarce resources available.
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-104 - Lung Cancer Patients Derived Xenografts: Prospective Molecular Profiling and Potential Evaluation of Drug Resistance (ID 1278)
09:30 - 09:30 | Author(s): T. Mele
- Abstract
Background:
The discovery of “driver mutations” such as the Epidermal Growth Factor Receptor (EGFR) and the Anaplastic Lymphoma Kinase (ALK) has led to a remarkable improvement in the outcomes of lung adenocarcinoma, which accounts 50% of the non-small cell lung cancer (NSCLC) diagnoses. Up today, no druggable molecular targets have been identified for squamous carcinoma or small cell lung cancer, which are still treated with the “one-fits-all” therapeutic approach, as it is for a relevant percentage of adenocarcinomas too. The precise definition of molecular profile and, possibly, the description of predictive factors are research priority in the thoracic oncology field. The vast majority of preclinical data are based on in vitro studies, but cell lines models do not entirely reflect tumour characteristics and are hampered by genetic divergence from primary tumours. Patient derived tumour xenografts (PDTX) are a valuable alternative to closely reproduce tumour biology and to prospectively characterize in vivo mechanisms of cancer growth and therapeutic response. Through the generation of a cohort of lung cancer xenopatients, the project aims to confirm the reliability of such models in this disease and to prospectively characterize its biomolecular features.
Methods:
Metastatic and early stages lung cancer cases are considered for the enrolment. Written informed consent is requested from each patient. Fresh tumour tissue from lung biopsies or lung resections is collected and kept in serum free medium (4° C), embedded in 20% matrigel and subcutaneously engrafted into NSG and NOD SCID mice, within 24 hours from sample collection. The exponentially growing tumours are passaged subcutaneously to other mice for a second passage after which they are archived for subsequent analyses (formalin fixed, snap frozen and RNA later). Each sample from surgical resection is also stored to create a DNA lung cancer bank.
Results:
Fourteen samples from TC-guided lung biopsies and sixty-six from radically resected NSCLC were engrafted in NSG and NOD SCID mice lineage in a 1:1 ratio. Due to the low engraftment rate and high morbidity observed in NGS mice in the first 73 samples, subsequent engraftments and expansions were performed in NOD SCID mice only. The overall engraftment rate in biopsy samples was 0 % in NGS and 7.14 % in NOD SCID mice as opposed to 0 % in NGS and 27,27 % in NOD SCID for surgical samples (50% adenocarcinomas, 44,45% squamous carcinomas and 5,55% sarcomatoid carcinomas). Nineteen samples underwent the second passage: of those, 10 samples have been archived after the second successful passage and will be used for further analyses.
Conclusion:
The trial is still ongoing and a longer follow-up is needed. In biopsy-derived samples, engraftment is deeply limited by the paucity of tissue. The results of this study will possibly confirm the reliability of PDTX in lung cancer and provide prospective biomolecular characterization for different histological types.
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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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P3.04-060 - Non Small Cell Lung Cancer in Women: Identification of Molecular Biomarkers Towards Sex Specific Tailored Treatments (ID 1272)
09:30 - 09:30 | Author(s): T. Mele
- Abstract
Background:
Lung cancer is the leading cause of cancer mortality in both men and women in more developed countries, with a four-fold increase in lung cancer in women in US over the past 30 years. This was confirmed in Europe where, in the last 5 years, lung cancer mortality fell in men (−6%) and increased in women (+7%). Several studies documented sex differences in lung cancer in terms of clinical presentation, survival, pathological patterns and treatment related toxicities; younger age at diagnosis, higher frequency of adenocarcinoma histology, different metabolism of tobacco-related carcinogens, differential gene expression are commonly seen in women. Furthermore, previous studies showed in female gender the expression of functional aromatase enzyme in lung tumor tissues as well as the interaction between Estrogen Receptors (ERs) and Epidermal Growth factor Receptor (EGFR) pathways in lung cancer cells. The aim of this study is to collect a prospective series of advanced stage non small cell lung cancers (NSCLC), to identify, through the Next Generation Sequencing (NGS) technology, potential gender sex differences of selected tumor-associated genes, assessing their both mutational status and gene expression levels.
Methods:
One hundred patients, including 50 women and 50 men, with newly diagnosed stage IV NSCLC will be prospectively enrolled. Smoking history, clinical and anamnestical data will be collected for all patients. Female patients will also provide obstetrical-gynecological anamnesis, while men will provide urological one, if present. Formalin fixed, paraffin embedded diagnostic sample of each patient will be collected and sectioned to obtain: a DNA genomic library to define the mutational profile of a selected panel including 50 tumor-associated genes, a mRNA library to obtain gene expression levels of the corresponding transcripts and protein expression of estrogen receptor Beta (ERß) and DNA repair enzyme ERCC1. Immunohistochemistry reaction, for both ERCC1 and ERβ, will be scored according to the H-score method. NGS analyses will be performed by means of the Ion Torrent Personal Genome Machine (PGM, Life Technologies, Grand Island, NE). Tumor tissues will be tested with commercial library kits: Ion AmpliSeq Cancer Hotspot Panel v.2 to investigate 50 cancer-associated genes and significant gene variations will be further confirmed using Sanger Sequencing method; Ion AmpliSeq™ RNA Cancer Panel to define also gene expression of the same 50 cancer-associated genes (Life Technologies). Correlations among mutational profile, transcriptional pattern, protein levels and clinico-pathological characteristics will be assessed.
Results:
Not Applicable
Conclusion:
Lung cancer incidence in women is increasing worldwide and genetic predisposition, sex hormones or specific molecular features could all account for the clinical differences observed between females and males. Up to the current date, the clinical approach to lung cancer treatment does not rely on gender. The identification of differential status of specific biomarkers can deepen knowledge on the molecular basis of this disease, guiding clinicians towards sex-based treatments.
