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M. Samarzija
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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. Samarzija
- 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: 2
- 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. Samarzija
- 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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P3.04-103 - Evaluation of the TGF Beta Superfamily Member Activin-A as a Novel Circulating Prognostic Marker in Lung Cancer (ID 2720)
09:30 - 17:00 | Author(s): M. Samarzija
- Abstract
Background:
Identification of biomarkers that can facilitate early detection and therapeutic decision making in lung cancer (LC) is urgently needed. Growth factors of the activin family are deregulated in a number of malignancies including thoracic tumors. Recent studies provided data regarding the tumor tissue expression levels of activin-A in lung adenocarcinoma (ADC): High activin-A expression was associated with poor prognosis, enhanced metastasis and shorter progression-free survival in stage I ADC. Since activin-A is secreted to the circulation and can be detected in plasma, this study aims to determine, for the first time, the value of circulating activin-A as a biomarker in LC patients.
Methods:
Plasma samples from patients with small cell lung cancer (SCLC, n= 79), ADC (n=87) and squamous cell carcinoma (n=36) were collected between 2009 and 2013 at the time of diagnosis or before surgical resection. Additional samples, serving as age- and sex-matched controls, consisted of individuals without malignancies (n=66). Measurement of samples was performed using the Quantikine activin-A Elisa kit (R&D Systems) and all statistical analyses were performed using the PASW Statistics 20.0 package and GraphPad Prism 6.0.
Results:
Mean plasma activin-A levels (PAL) (pg/ml) were the following: 628,8±38,42 (ADC, range: 112,4-1875), 613,5±68,22 (SCC, range: 194-2076), 771±77,06 (SCLC, range: 174,1-3627) and 433,3±16,27 (controls, range: 194,1-808,8). A gender-related variation in the PAL of controls (female (n=31, mean PAL 469,5±24,54 (range 212,95-808,79)) vs. male (n=35; mean PAL 401,3±20,49 (range 194,1-759,02)), p= 0.0319) was observed. PAL was significantly increased in patients with ADC (p=0.0009), SCC (p=0.0061) and SCLC (p<0.0001) compared to controls. There was no difference in PAL with regard to patients´ age, gender, BMI, smoking status or other co-morbidities in all 3 LC types. A significant TNM stage-dependent increase of PAL was observed in all 3 LC types. PAL was elevated in T3 SCC, in T4 ADC and in T3 and T4 SCLC. PAL was also clearly associated with N status and metastatic disease in all 3 LC types. Importantly, in case of SCLC, PAL was associated with extensive disease and showed metastatic site specificity. In ADC patients, elevated PAL was associated with significantly worse overall survival (OS) (p<0.0001). Of note, in locally advanced ADC, elevated PAL also proved to be a significant negative prognosticator (p=0.048). Moreover, elevated PAL was associated with a poor OS in SCLC patients (p=0.0009). Multivariate analysis revealed that PAL was an independent prognostic factor in ADC and SCLC patients. Survival and multivariate analysis data of the SCC cohort will be presented at the conference. ROC curve analysis showed an AUC of 0.691 in SCLC and an AUC of 0,657 in ADC for PAL.
Conclusion:
Our findings suggest that PAL is significantly elevated in a disease stage-dependent manner in LC patients. Moreover, elevated PAL is associated with poor prognosis in ADC and SCLC patients.
