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A. Kotsakis
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MINI 37 - SCLC Therapy (ID 165)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Small Cell Lung Cancer
- Presentations: 1
- Moderators:D. Ettinger, G.R. Simon
- Coordinates: 9/09/2015, 18:30 - 20:00, 605+607
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MINI37.08 - Pazopanib as Second Line Treatment of Platinum Sensitive SCLC Patients: A Multicenter Phase II Trial of the Hellenic Oncology Research Group (ID 1683)
18:30 - 20:00 | Author(s): A. Kotsakis
- Abstract
- Presentation
Background:
Pazopanib is a small anti-angiogenic molecule inhibiting the tyrosine kinase of VEGFR‑1, VEGFR‑2, VEGFR‑3, PDGF, and c‑kit. An increased angiogenesis and VEGF expression has been reported in SCLC which is correlated with disease dissemination and poor prognosis. A multicenter phase II study of second line pazopanib in patients with SCLC was conducted.
Methods:
Patients with histologically confirmed SCLC who relapsed at least 3 months after the completion of front line VP-16/CDDP chemotherapy (platinum sensitive disease) were enrolled. Eligible patients should have measurable disease and ECOG performance status (PS) 0-2. Treatment consisted of daily p.o. pazopanib 800 mg in cycles of 28 days until disease progression. The primary endpoint was progression-free rate (PFR) at 8 weeks since anti-angiogenic factors are not associated with objective tumor shrinkage.
Results:
Thirty seven out of 39 enrolled patients (2 pts are still ongoing) were evaluable for response and toxicity. The median age was 65 years (range 39-82); male=33 pts; PS 0=22 pts; PS 1=15 pts. Eleven (28.2%) patients had only local relapse. The median interval from previous treatment was 5.4 months (3.0-38.2). One (3%) CR, 10 (26%) PR and 10 (26%) SD were documented, for an overall progression free rate (PFR) of 55% (95% CI: 39.4- 71.2%). The median PFS and OS was 3.7 and 10.6 mo, respectively, while the estimated 1-year survival was 58% (median follow up= 18.9 mo). Grade 4 adverse events (AEs) included neutropenia (n=2 pts) and diarrhea (n=2 pts) whereas grade 3 AEs were fatigue (n=4pts), nausea (n=1 pt), diarrhea (n=2 pts), hand-foot syndrome (n=1 pt) and transaminasaemia (n=1 pt). Epistaxis (gr 2) was reported in 3 pts, proteinuria (gr 2) and hypertension (gr 2) in 2 pts each. There were no treatment-related deaths.
Conclusion:
Second line treatment with pazopanib of patients with sensitive SCLC, was well-tolerated and resulted in a promising overall survival and disease control rate, including objective responses.
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ORAL 18 - Non PD1 Immunotherapy and Angiogenesis (ID 114)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:C. Butts, K. Reckamp
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F1+F2
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ORAL18.06 - Effect of Anti-VEGF Therapy on MDSCs' Population in the Peripheral Blood of Non-Small Cell Lung Cancer (NSCLC) Patients (ID 689)
10:45 - 12:15 | Author(s): A. Kotsakis
- Abstract
- Presentation
Background:
Bevacizumab is an anti-VEGF monoclonal antibody approved for the treatment of non-squamous NSCLC. It is widely accepted that immunosuppressive mechanisms dominate in patients (pts) with solid tumors, including NSCLC. MDSCs are a heterogeneous population of immature cells of myeloid origin, whose expression is induced by VEGF. We recently identified two monocytic and one granulocytic MDSC subpopulation which are significantly increased and functional in the peripheral blood of NSCLC pts.
Methods:
Peripheral blood immune cells from 46 pts with unresectable NSCLC were analyzed by flow cytometry before the initiation of chemotherapy and after 3 cycles. Changes in the frequencies of the three MDSCs subpopulations were correlated with clinical outcome. Isolated MDSCs were co-cultured with T cells in order to confirm their functionality through estimation of IFN-γ secretion.
Results:
At diagnosis, the CD15(-) monocytic MDSCs’ levels were significantly increased in male pts (p=0.03) and in smokers (p=0.01). Overall, chemotherapy had no effect on the frequency of the distinct MDSC subpopulations. However, after 3 cycles of therapy, levels of all three MDSC subpopulations numerically decreased in responders (n=11) compared to non-responders (n=4). In addition, bevacizumab-based chemotherapy regimens significantly reduced the frequency of the granulocytic MDSC subpopulation when compared to the effect of non-bevacizumab based therapy (p=0.02). Lastly, suppression of IFN-γ secretion in vitro, confirmed the inhibitory effect of isolated MDSCs on T-cell cytotoxic capacity.
Conclusion:
These data indicate that although chemotherapy has no effect on the levels of different immunosuppressive MDSC subpopulations, bevacizumab–based regimens seem to exert an effect on the granulocytic MDSC subpopulation. Additional studies are needed in a larger cohort of pts in order to document its impact in the clinical outcome of NSCLC pts.
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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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P1.01-014 - Long Term Clinical Benefit of EGFR wt in Advanced NSCLC Patients Treated for Long Time with Salvage Erlotinib. A Retrospective Analysis (ID 687)
09:30 - 17:00 | Author(s): A. Kotsakis
- Abstract
Background:
Erlotinib (E) has been approved for the management of NSCLC patients (pts) after failure of the first or subsequent line of chemotherapy. Although the efficacy of E is clearly associated with the presence of drivers EGFR mutations, there is a subset of pts with EGFR wild type (EGFR wt) tumors who impressively respond. We retrospectively analyzed the clinical and pathological characteristics of a group of pts with unresectable EGFR wt NSCLC treated for a prolonged period with salvage (≥ 2[nd] line setting) E.
Methods:
Patients with unresectable EGFRwt NSCLC who received ≥ 2[nd] line treatment with E without disease progression for at least 6 months, were sought from the database of HORG. Pts with available tumor material were molecularly (KRAS, BRAF, PI3K, HER2 mutations and ALK-EML4 translocation) characterized.
Results:
Among 1450 pts treated in different HORG’s collaborating centers (from 2004-2013), 44 (3.03%) received E for >6months (median: 10.1 mo; range, 6.0-36.5). 17 were women, 57% had no history of smoking, 42 had a PS (ECOG) of 0-1; 16% had squamous cell histology and 73% adenocarcinoma. KRAS mutations were detected in 20.5% (9/42 tested) of the pts, PI3K mutations in 9% (3/30 tested) and ALK-EML4 translocation in 9.5% (2/21 tested); there was no patient with HER2 or BRAF mutated tumor. 11(25%) pts experienced a partial response and 26 (59%) stable disease (Tumor growth control rate 84%). The median PFS and OS was 10.1 (6.0-40.6) and 24.1 (6.0- 89.1) months, respectively. Pts with KRAS wt tumors had a significantly (p=0.018) better OS compared to pts with KRAS mutant tumors. There was a trend of improved PFS (p=0.083) and OS (p=0.053) in favor of pts with adenocarcinoma compared to pts with squamous cell carcinoma.
Conclusion:
Treatment with E significantly improves the clinical outcome in a subset of NSCLC pts with EGFR wt tumors. Pts with non-squamous pathology and no smoking history seem to benefit most from such therapy. KRAS mutation was the only molecular alteration correlated with the clinical outcome. Further molecular analysis of these pts could help to more appropriately define this particular group of patients.
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P2.01 - Poster Session/ Treatment of Advanced Diseases – NSCLC (ID 207)
- Event: WCLC 2015
- Type: Poster
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P2.01-083 - Prognostic Significance of CK19mRNA Positive Cells in the Peripheral Blood of Patients with Advanced Non Small Cell Lung Cancer (NSCLC) (ID 760)
09:30 - 17:00 | Author(s): A. Kotsakis
- Abstract
Background:
Circulating Tumor Cells (CTCs) have been shown to be a useful prognostic tool in several cancers. Non-small-cell-lung cancer (NSCLC) lacks validated prognostic biomarkers and, thus, this study aimed to explore the sensitivity and clinical significance of the detection of CK19mRNA (+) CTCs in NSCLC patients.
Methods:
Peripheral blood was obtained from 642 patients with previously untreated stage IIIB/IV NSCLC and from 455 patients after the completion of 1[st] line chemotherapy. RNA extracted from the Calu-3 and ARH-77 cell lines was used as positive and negative controls, respectively. The detection of CK19mRNA-positive cells was performed using an RT-qPCR assay.
Results:
The analytical detection limit of the method was found to correspond to 0.42 Calu-3 cell equivalents/5μg RNA. One hundred and sixty seven (26.0%) patients had detectable CK19mRNA (+) CTCs at baseline; the detection of CK19mRNA (+) CTCs post chemotherapy was associated with significantly decreased PFS and OS (PFS: 2.6 vs 3.8 months, p=0.008; OS: 5.7 vs 10.0 months, p=0.006). Multivariate analysis revealed that gender, performance status and the detection of CK19mRNA (+) CTCs post chemotherapy emerged as independent factors associated with reduced PFS (HR=1.350, p=0.010) and OS (HR=1.608; p=0.001).
Conclusion:
Detection of peripheral blood CK19mRNA (+) CTCs post chemotherapy is an adverse prognostic factor correlated with poor clinical outcome in patients with stage IIIB/IV NSCLC.
