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A. Catino
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P1.02 - Poster Session with Presenters Present (ID 454)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.02-045 - Discordance (FISH+, IHC-) between FISH and IHC Analysis of ALK Status in Advanced Non Small Cell Lung Cancer (NSCLC): A Unexpected Issue in 7 Cases (ID 5757)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
Anaplastic lymphoma kinase (ALK ) rearrangement represents a landmark in the targeted therapy of NSCLC. Several reports showed that IHC is sensitive and specific to detect ALK protein expression, possibly alternative to ALK FISH assay. In this study the concordance between the ALK status by FISH and IHC assay has been determined in a series of 95 advanced NSCLCs; discordant cases were evaluated on the basis of the percentage and the rearrangement pattern of ALK.
Methods:
95 lung NSCLC specimens were tested for ALK rearrangements by IHC assay (ALK D5F3 antibody Ventana,CE-IVD system) and by fluorescence in situ hybridization (FISH). Clinical characteristic and response to crizotinib were reviewed.
Results:
Seven cases (7.3%) showed discordant results with ALK FISH-positive and IHC negative. Among these cases the mean number of FISH positive rearranged nuclei was 40.2% (range 20-54%). All cases showed coexistent split signals pattern positivity with mean percentage 19.1% (range 10-32%.), 5' deletions pattern positivity with mean percentage 21.7% (range 12-34%) and one case also had gene amplifications pattern positivity with percentage of 64%. The polysomy was observed in all cases with mean percentage of 45.7% (range of 16-72%). Five patients with discordant ALK FISH and IHC results received crizotinib; of them, four progressed and one has stable disease.
Conclusion:
In most of discordant cases, a coexistent complex pattern of rearrangements (deleted, invertited and amplified/polysomic patterns) of ALK positive cells in FISH analysis was observed; these complex rearranged cases were not detectable by IHC, probably due to the lack of protein expression. Considering that crizotinib inhibits the ALK protein and not specifically ALK rearrangements, it could be speculated that NSCLCs without IHC ALK expression could be not sensitive to crizotinib. The ALK FISH+/IHC negative discordant group showed a loweer percentage of nuclei positive for ALK rearrangement (19.1% in split signals and 21.7% in 5' deletions) as compared with 64% of gene amplification in one case and with polysomy (45.7%) observed in all cases. These preliminary data highlight the role of IHC analysis and of the percentage of the genetic pattern of ALK rearranged cells in FISH analysis to select patients for anti ALK treatment. Further investigation is suggested about the correlation of complex mutational findings and clinical outcome.
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P1.06 - Poster Session with Presenters Present (ID 458)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.06-046 - Can We Better Manage Advanced NSCLC in the Elderly with the New Therapeutic Agents? Preliminary Analysis of a Real-Life Multicenter Study (ID 5814)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
Systemic treatment of NSCLC has profoundly changed over the past years with novel therapeutic strategies recently implemented in clinical practice. Benefit of these novel agents in elderly patients (pts) is uncertain, given the paucity of prospective data in this population. Moreover, elderly pts are often undertreated, due to comorbidities and toxicity concerns. Therefore, we aimed to evaluate the access, safety and outcome with novel therapeutic agents in pts ≥ 70 years (yrs).
Methods:
We planned an observational study to retrospectively evaluate consecutive elderly patients (≥ 70 yrs) with metastatic NSCLC treated at 9 Italian Centers between January 2014 and December 2015. Data collected include clinical and pathological characteristics, treatment types, safety and outcome report.
Results:
220 patients with stage IV NSCLC were included in this preliminary analysis (53% IVa, 47% IVb). Median age was 74,5 (range 70-85) and 69% were male. 15% of pts aged 80 years or older. ECOG PS was 0, 1, 2 in 37%, 51% and 12% of pts, respectively. According to comprehensive geriatric assessment, 59% of pts were fit, 28% vulnerable and 13% frail. Histology was 23% squamous cell carcinoma, 72% non-squamous cell carcinoma and 5% NOS. EGFR mutation was diagnosed in 24% of cases; 1,4% and 1% of pts had ALK and ROS-1 translocations, respectively. 90% of pts received a systemic therapy: 48% a platinum doublet chemotherapy (CHT), 27% a mono-CHT, 25% an EGFR tyrosine kinase inhibitor (TKI). Only 1% of pts were treated with antiangiogenic drugs. Immunotherapy (IT) was administered in 16% of all treated pts. 7% of pts received only BSC. Second- and third-line treatment were given to 44% and 8% of pts, respectively. 51% of pts who received second line treatment and 60% of pts treated with a third line therapy had a novel therapeutic agent (II line TKI 20%, IT 31%; III line TKI 33%, IT 27%). 31% of pts were included in clinical trials. A dose reduction was reported in 41% of therapies and the discontinuation rate was 9%. Survival data are not mature at this time.
Conclusion:
Our data, albeit preliminary, suggest an evolution in the management of NSCLC in the elderly. The interesting activity and the good safety profile encourage the use of novel agents also in this setting of NSCLC. Adequate selection of elderly pts and personalized approach are still matters of debate. Use of adapted schedule and dose reduction could warrant a good compromise between safety and efficacy.
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P2.02 - Poster Session with Presenters Present (ID 462)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.02-061 - Role of MMP-2-1306C/T in Onset of Hematological Toxicity in Lung Cancer Patients Receiving First Line Platinum Based Therapy (ID 4589)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
Lung cancer is the most common and lethal cancer worldwide. Totally, about 85% of lung cancer cases could be classified as Non-Small Cell Lung Cancer (NSCLC) and most are diagnosed at advanced stage. Matrix Metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components playing a key role in the process of tumor growth/metastasis. Genetic variants in matrix metalloproteinase-2 (MMP-2) gene may influence the biological function of this enzyme changing his role in carcinogenesis, hematopoietic recovery from chemotherapy toxicity and cancer progression. This study has investigated the association of single nucleotide polymorphism (-1306C/T) in the MMP-2 promoter sequence, and the link with a strong hematological toxicity in lung cancer patients receiving first-line, platinum-based chemotherapy.
Methods:
Forthy-seven patients (36 men and 9 women) with IIIA/IV NSCLC stage were enrolled; information about hematologic toxicity (thrombocytopenia, neutropenia, anemia), gastrointestinal toxicity (nausea/vomiting), and smoking habits were collected through the clinical charts. Genotyping was performed using direct DNA sequencing.
Results:
25/47 patients (53%) had the CC genotype, 8/47 (17%) patients had CT genotype and 14/47 (30%) had TT genotype. A grade 2-3 anemia associated to grade 2-3 thrombocytopenia and/or G2-3 neutropenia was observed in 12/22 CC patients compared with only 4/14 TT patients and 3/8 CT patients (p<0.001), after platinum-based therapy; patients with genotype TT showed a better response to treatment as compared with those carrying CT or CC genotype. Besides, this study showed that heavy smokers had a higher allelic frequency CC and this could indicate a possible correlation between genetic polymorphism, smoking status, and clinical outcome.
Conclusion:
These preliminary findings suggest that MMP-2 promoter polymorphism could be correlated with therapeutic response, in particular, the patients with TT genotype seem more protected from the hematological toxicity due to chemotherapy.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 3
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-085 - Neutrophil/Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer: Correlation with Prognosis and Response to Anti-PD1 Therapy (ID 5772)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
The Neutrophil/Lymphocyte ratio (NLR), calculated from peripheral blood tests, represents an independent and easily available prognostic biomarker in numerous cancers, including lung cancer. This study aimed to investigate the prognostic role and the correlation with the therapeutical response of baseline NLR in patients with advanced Non-small cell lung cancer (a-NSCLC) submitted to anti-PD1 therapy.
Methods:
Nivolumab (3 mg/kg intravenously by rapid injection every 14 days) was administered to 47 patients (6 women , 41 men) with a-NSCLC. The mean age of patients was 47 years (range 40-83, SD 9.07), while the histotype was: 28 adenocarcinoma, 18 squamous, 1 adenosquamous. 68% of patients were current/former smokers. 25/47 patients (53%) received more than 2 previous lines of therapy. The baseline absolute neutrophil and lymphocytes count and the Neutrophil /Lymphocytes ratio were recorded. Time to progression (TTP) was statistically evaluated by Kaplan-Meyer method; univariate analysis was conducted by Cox regression method .
Results:
A median of 7.8 (range 1-20) cycles of therapy was administered . A better TTP (3 months vs 1,5 months; Cox regression rate (Hazard Ratio ) 1.000118, p= 0.003 (CI 1.000041-1.000195) was observed in patients with a lower absolute baseline Neutrophil count (Less than 7500); conversely, a higher absolute Lymphocyte baseline count was linked with a longer TTP (3.7 months vs 1.8; Cox regression rate (HR) 0.9994947, p= 0.055 (CI 0.9989785-1.000011). NLR was correlated with Time to Progression (TTP), that was longer in patients with NLR less than 4 (3.71 months vs 1.87 ; Cox regression rate (HR) 1.144335, p= 0.001 (CI 1.068327-1.22575) (Figure) Figure 1
Conclusion:
These preliminary findings highlight the correlation between the NLR and clinical outcome of a-NSCLC patients treated with anti-PD1. Further investigation in this setting is warranted, both to confirm the prognostic role and to investigate if NLR and the microenviromental inflammatory alterations could predict the response to immune-checkpoint inhibitors.
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P3.02c-094 - Italian Nivolumab Advanced Squamous NSCLC Expanded Access Program: Efficacy and Safety in Patients with Brain Metastases (ID 5144)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
The prognosis of NSCLC patients (pts) with brain metastases is still quite poor. These pts usually do not meet the inclusion criteria to be enrolled in clinical trials. Nivolumab Italian Expanded Access Program (EAP) allowed this subpopulation of pts to be included, providing the opportunity to evaluate safety and efficacy of nivolumab treatment in pts with brain metastases.
Methods:
upon physician written request, nivolumab was provided to pts who met the following inclusion criteria: aged ≥18 years, who had received a diagnosis of squamous NSCLC, and who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV squamous NSCLC. Nivolumab is administered intravenously at the dose of 3 mg/kg every 2 weeks for a maximum duration of 24 months. We describe efficacy and safety of nivolumab in pts who received at least one dose. Adverse events were monitored using Common Terminology Criteria for Adverse Events.
Results:
from our cohort of 372 patients diagnosed with squamous NSCLC, we report the results of 38 (10.2%) pts with treated and asymptomatic brain metastases. In these pts, with median follow-up of 4.5 months and median number of doses of 6 (range, 1–18), disease control rate was 47.3%, including 1 complete response, 6 partial responses and 11 stable diseases. Treatment beyond RECIST defined progression was allowed, under protocol defined circumstances, in 4 pts. Median progression-free survival was 5.5 months, and overall survival was 6.5 months (data lock of April 2016). Out of the 38 pts included, only 1 discontinued treatment due to AE (2.6%), whereas 21 pts (55.3%) discontinued treatment for non-toxicity related reasons.
Conclusion:
although preliminary, these results demonstrate efficacy of nivolumab in squamous NSCLC pts with brain metastases. Safety of nivolumab in these pts is consistent with previously reported data from clinical trials. These results suggest nivolumab could be beneficial in this subpopulation of pts with unfavourable prognosis.
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P3.02c-096 - Use of Nivolumab in Elderly Patients with Advanced Squamous NSCLC: Results from the Italian Expanded Access Programme (EAP) (ID 5706)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
The efficacy and safety of nivolumab in patients with squamous NSCLC (sq-NSCLC) have been demonstrated in several trials including the phase 3, randomized, controlled CheckMate 017 study whose results led to the approval of the product for this indication. However, data on the use of nivolumab in the real world setting is still limited and collecting it is paramount. The Italian nivolumab EAP for sq-NSCLC represents an important source of information in that respect. The current analysis describes results of the use of nivolumab in the group of EAP patients aged >75 years.
Methods:
Nivolumab was provided upon physicians’ request for patients aged ≥18 years who had relapsed after a minimum of one prior systemic treatment for stage IIIB/stage IV Sq-NSCLC. Nivolumab 3 mg/kg was administered intravenously every 2 weeks for <24 months. Patients included in the analysis received ≥1 dose of nivolumab and were monitored for adverse events (AEs) using Common Terminology Criteria for Adverse Events.
Results:
70 out of 372 (18.8%) patients with advanced Sq-NSCLC participating in the EAP in Italy were ≥75 years old and 68 of them were evaluable for response. With a median number of doses of 7 (range, 1–20) and a median follow-up of 4.7 months, the disease control rate was 42.9%, including 13 patients with a partial response and 17 with stable disease. 16 pts were treated beyond RECIST-defined progression and 5 of them achieved disease control. As of April 2016, the median progression-free survival and median overall survival among those elderly patients were 3.2 and 7.6 months, respectively. Among 70 pts, 41 pts (58.6%) discontinued treatment for any reason except toxicity; 8 out of 70 discontinued due to AE (11.4%).
Conclusion:
This analysis, conducted on elderly patients with sq-NSCLC in a real life setting, suggests that nivolumab is an effective and well tolerated treatment for this special population.
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P3.05 - Poster Session with Presenters Present (ID 475)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Palliative Care/Ethics
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.05-004 - Psycho-Social Function and Caregiver's Burden in Patients with Advanced Lung Cancer (ID 4469)
14:30 - 14:30 | Author(s): A. Catino
- Abstract
Background:
Patients with advanced lung cancer (a-LC) are often characterized by high tumor burden and comorbidities also correlated to anxiety and depression. The Authors report the preliminary results of a pilot experience on early simultaneous interdisciplinary palliative approach in a-LC patients, referring to the Thoracic Oncology outpatient department of a Clinical Cancer Center. The first aim of the study was to evaluate the quality of life and health status of these patients. Secondly, the caregiver’s burden of care has been investigated.
Methods:
32 patients with a-LC (mean age 65 years; Standard Deviation (SD)= 8,3) were enrolled. Psychological distress and health status were assessed by Hospital Anxiety and Depression Scale (HADS), and Short Form 36 Health Survey (SF-36). 23 caregivers (mean age 57 years; SD= 14) compiled the Caregiver Burden Inventory (CBI) to evaluate their burden of care.
Results:
55% of patients showed higher score in the total scale of anxiety and depression. 35% of caregivers reported higher level of burden. Among caregivers, women reported higher levels of feelings of fatigue (Physical Burden) as compared to men (F= 4,45, p = 0.05) that reported higher levels of Emotional Burden (F= 7,55, p <0.05); the patient’s sons reported higher scores of Emotional Burden with respect to partners (F= 4,75, p <0.05). Finally, younger caregivers showed higher scores about the Social (F= 10,73, p <0.01) and Emotional Burden (F= 26,6, p <0.01). The correlations among the questionnaires are shown in table 1.
Conclusion:
In our sample of a-LC patients, psychological distress was correlated with general quality of life. The highest burden reported by caregivers was linked to the time dedicated to the assistance and to the feeling of fatigue. Our findings suggest to provide psychological support to caregivers, in particular for women to achieve a private and personal space, and for sons to the emotional management.Figure 1
