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M. Jakopovic
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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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P1.01-063 - Efficacy and Safety of Erlotinib in Squamous Cell Lung Cancer (ID 1327)
09:30 - 17:00 | Author(s): M. Jakopovic
- Abstract
Background:
Erlotinib is epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor which showed efficacy and tolerability in patients with advanced non-small cell lung cancer (NSCLC), especially in patients which harbor activating mutations in EGFR. However, erlotinib also showed efficafy in patient with unknown or wild type EGFR mutation status. The iam of the study was to determine safety and efficacy of erlotinib in patients with advanced (stage IIIB and IV) squamous NSCLC.
Methods:
patients with advanced squamous NSCLC who had failed prior chemotherapy were treated with oral erlotinib 150 mg daily until disease progression or unaccaptable toxicity. Data was analyzed retrospectively.
Results:
a total of 122 patients (107 men and 15 women, mean age 62±8 years) with advanced squamous NSCLC were enrolled in the study from 2006 to 2012 in 14 centers throughout Croatia. More than 50% of patients were active smokers at time of enrollment. Most of the patients had performance status ECOG 1 and 2 (91%). Vast majority of patients were treated with erlotinib in third line setting. After cycle 2, 10% of patients had partial response (PR), and 45% of patients had stable diseases. In total, 55% of patients had disease control after cycle 2. Progression free survival (PFS) was 3.7 months in overall population. Statistically significant differences in PFS were recorded according to response to treatment; patients with PR after two cycles had PFS of 6.2 months comparing to patients with progressive disease (PFS 2.0 months, p<0.001). Patients with better ECOG status (ECOG 1 and 2) had trend to improved PFS (3.8 vs 1.9 months) compared to ECOG 2 and patients with rash after cycle 2 also showed trend to improved PFS (4.1 vs 2.4 months) compared to no rash. There were no grade 3 and 4 toxicities noticed during the study. Overall survival in our study was meaningfully prolonged.
Conclusion:
erlotinib as a single agent showed efficacy in treatment of patients with squamous cell lung cancer without significant toxicities. The best predictive factor of response to treatment was response to erlotinib after 2 months of treatment.
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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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P3.04-059 - Non-Small Cell Lung Cancer Mutation Analysis in Purely Caucasian Croatian Population (ID 1575)
09:30 - 17:00 | Author(s): M. Jakopovic
- Abstract
Background:
Molecular profiling in lung cancer patients is crucial before starting treatment. Driver mutations in EGFR and ALK genes are targets for tyrosine kinase inhibitors. Mutation rate in domain of EGFR, ALK and KRAS genes varies between populations of lung cancer patients. The aim of the study was to analyze rates of mutation in these genes in purely Caucasian Croatian population.
Methods:
Reflex testing was performed on all non-squamous NSCLC in a period of 6 months, regardless of staging and received therapy. There were altogether 387 patients with adequate (histological and cytological) material for testing. EGFR mutations were tested first (cobas® EGFR Mutation Test, Roche), all negative were than tested for KRAS mutations (cobas® KRAS Mutation Test, Roche), and double negative samples were than tested for ALK mutation using immunohistochemistry (IHC) (clone D5F3, Ventana).
Results:
Out of 387 samples 57 had EGFR mutation (14.72%). Most common mutation was exon 19 deletion (23/57, 40.35%), while 8/57 (14.04%) had two simultaneous mutations. KRAS mutations were present in 158 samples out of 330 samples that were tested (47.88%). ALK immunohistochemistry was performed on 172 double negative samples, resulting in 12 positive cases (6.98%). When calculating with the whole cohort, we had 14.72% of EGFR positive cases, 40.82% with KRAS mutations and 3.10% of ALK IHC positive cases.
Conclusion:
gene changes rates in EGFR and ALG gene are in Croatian lung cancer patients in concordance with previously reported rates in Caucasian population, while KRAS rates are higher than previously reported. For the first time, rates of genetic changes are reported for representative sample of purely Caucasian Croatian population.
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P3.08 - Poster Session/ Thymoma, Mesothelioma and Other Thoracic Malignancies (ID 226)
- Event: WCLC 2015
- Type: Poster
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.08-007 - Fibulin-3: A Potential Prognostic Biomarker in Malignant Pleural Mesothelioma? (ID 1668)
09:30 - 17:00 | Author(s): M. Jakopovic
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a highly aggressive asbestos-induced cancer arising from the mesothelium lining the thoracic cavities. The definitive diagnosis of MPM in most instances depends on the availability of a biopsy. A number of biomarkers have been proposed to assist in making the MPM diagnosis but none of them has yet reached the accuracy required for routine clinical use. Among the candidates is the secreted extracellular glycoprotein Fibulin-3 (FBLN3) (Pass et al, NEJM 2012; 367(15)). In this study, we have further investigated the potential of FBLN3 to serve as a biomarker for MPM.
Methods:
Cellular and secreted FBLN3 was measured (ELISA) in MPM and normal mesothelial cell lines, plasma of xenograft tumour-bearing mice, plasma from two independent series of MPM and non-MPM patients, and in malignant and non-malignant pleural effusions. The diagnostic and prognostic potential of FBLN3 was assessed by receiver operating characteristics curve analysis and the Kaplan-Meier method, respectively.
Results:
FBLN3 levels were significantly higher in MPM cells than in mesothelial cells, with a strong correlation between secreted and cellular levels. Human FBLN3 was also detectable in the plasma of tumour-bearing mice, suggesting that MPM cells were the origin of circulating FBLN3. Plasma FBLN3 levels found in MPM patients were lower than previously reported (Pass et al, NEJM 2012; 367(15)), but were comparable to those appearing in subsequent validation studies (Creaney et al, Thorax 2014; 69(10), Corradi et al, Anticancer Res 2013; 33(12)). Plasma FBLN3 was significantly elevated in MPM patients from a Sydney cohort, but far less in a Vienna cohort and the diagnostic accuracy of FBLN3 was insufficient in both cohorts [63%, (95%CI: 50.1-76.4) and 56% (95%CI: 41.5-71.0), respectively]. FBLN3 levels found in pleural effusions were comparable to those reported in previous studies, but the difference between cases and controls did not reach significance. In our series low levels of pleural effusion FBLN3 were again associated (p=0.002) with prolonged survival. In multivariate analysis taking histological subtype, age and gender into account FBLN3 remained significant with a hazard ratio of 9.92 (95%CI: 2.14–45.93).
Conclusion:
FBLN3 is overexpressed in MPM cell lines and may point to a potential oncogenic role for this protein. In contrast to the initial report linking FBLN3 to diagnosis in MPM, the levels of FBLN3 measured in plasma and pleural fluid of our series of MPM patients lacked diagnostic accuracy. However, the potential prognostic value of FBLN3 levels measured in pleural fluid was confirmed and in line with previous validation studies. These data underline the importance of validation studies for newly proposed biomarkers.
