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V. Georgoulias
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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)
11:39 - 11:50 | Author(s): V. Georgoulias
- 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 - 09:30 | Author(s): V. Georgoulias
- 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.
