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T. Jiang
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OA11 - Angiogenesis in Advanced Lung Cancer (ID 387)
- Event: WCLC 2016
- Type: Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:L.M. Montuenga, J. Heymach
- Coordinates: 12/06/2016, 11:00 - 12:30, Stolz 2
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OA11.07 - Combining Anti-Angiogenesis and Immunotherapy Enhances Antitumor Effect by Promoting Immune Response in Lung Cancer (ID 4985)
11:00 - 12:30 | Author(s): T. Jiang
- Abstract
- Presentation
Background:
Increasing studies have shown that anti-angiogenic therapy targeting VEGF/VEGFR2 axis are furnishing demonstrable therapeutic effect on lung cancer，but the treatment benefit is transitory in clinic, generally followed by restoration of tumor growth and disease progression. Blockade of VEGF/VEGFR2 pathway can not only induce anti-vascular effect, but also remodel the immunosuppressive tumor microenvironment probably due to promoting suppressive cells infiltration and enhancing PD-L1 expression, resulting in impairing antitumor immunity. Therefore, the current study aimed to investigate whether combining anti-angiogenic and anti-PD-L1 treatments can induce synergistic antitumor effect by enhancing antitumor immune response in murine lung cancer.
Methods:
We evaluated the antitumor effects of anti-VEGFR2 agent (apatinib) as monotherapy or in combination with anti-PD-L1 monoclonal antibody in a murine lung cancer model using Lewis lung cancer cells (LLCs). The changes of immune components in tumor and spleen were dynamically tested in different treatment groups and time points by flow cytometry and immunohistochemistry.
Results:
The results showed that VEGF/VEGFR2 blockade could retard tumor growth and inhibit tumor neovascularization via eradicating Foxp3[+ ]regulatory T cells (Tregs) and myeloid derived suppressive cells (MDSCs) and reducing the density of microvessels in the first two weeks of treatment. On the third week of apatinib monotherapy, the number of Foxp3[+ ]Tregs and MDSCs had increased again. Although VEGF/VEGFR2 blockade induced more tumor infiltrating lymphocytes (TILs), especially CD8[+] T cells, infiltrating into the tumor mass than control group (P < 0.01), the expression of PD-1 and PD-L1was also significantly upregulated than that control group (P < 0.01). Compared to apatinib monotherapy, combining treatment demonstrated that anti-VEGFR2 plus anti-PD-L1 therapy could significantly inhibit tumor growth (P < 0.01) by persistently eliminating Foxp3[+ ]Tregs and MDSCs. Furthermore, combining anti-VEGFR2 and anti-PD-L1 therapy could not only dramatically increase TILs infiltration, especially CD8[+] T cells, but also significantly reduce the expression of PD-1 and PD-L1.
Conclusion:
Simultaneous blockade of VEGF/VEGFR2 and PD-1/PD-L1 pathways induced a synergistic anti-tumor effect in-vivo, possibly through eliminating immunosuppressive components including Tregs and MDSCs and enhance antitumor immune response.
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-031 - Clinical Evaluation of Folate Receptor-Positive Circulating Tumor Cells Detection in Patients with Small Cell Lung Cancer (ID 5480)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
Small cell lung cancer (SCLC) is distinguished by extremely high numbers of circulating tumor cells (CTCs) in comparison to other malignancies, however, the role of CTCs in evaluating chemotherapy effect of SCLC is to be further clarified. The purpose of this study was to investigate the predictive and prognostic role of folate receptor–positive CTCs in unresectable SCLC.
Methods:
In this single-center prospective study, blood samples for folate receptor–positive CTCs analysis were obtained from 80 patients with chemotherapy-naive unresectable SCLC at baseline, after two cycles of chemotherapy, and on disease progression. All patients received chemotherapy with EC or EP regimen for at least two cycles. CTCs number at baseline, after chemotherapy and changes with chemotherapy were evaluated as predictive factors for chemotherapy effect, along with clinical characteristics.
Results:
Of all 80 patients, CTCs was detected at baseline as positive (CTCs>8.7 FU/3mL) in 67 patients, with the percentage of 83.8%, which was not associated with age, sex, smoking status or disease stage. In 72 evaluable patients, the disease control rate was 83.9% (52/62) and 50% (5/10) in CTCs positive and negative patients respectively (P=0.004). In CTCs positive patients, those harboring low levels of folate receptor (8.7
Conclusion:
CTCs number at baseline could be used as a useful prognostic biomarker for SCLC. Reduction in CTCs number with chemotherapy could predict better chemotherapy effect of SCLC.
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-092 - Predictive and Prognostic Effect of Circulating Tumor Cells in Non-Small Cell Lung Cancer Treated with Targeted Therapy (ID 4815)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
We propose a non-invasive, folate receptor (FR)–based circulating tumor cell (CTC) detection approach to interpret treatment response of targeted therapy between baseline and follow-up CTC values and the feasibility whether CTCs as a prognostic factor in advanced NSCLC with EGFR mutation/ALK translocation.
Methods:
This was a prospective, unopen-labeled, single-center trial. From July 25, 2014 to March 11,2016, 308 advanced NSCLC patients were enrolled to quantified CTC level by negative enrichment using immunomagnetic beads in combination with folate receptor-directed polymerase chain reaction(PCR) that allows secondary amplification of tiny amounts of CTCs in 3mL peripheral blood before the start of targeted therapy and after one month, every two months hereafter of treatment. Among whom, 272 NSCLC patients with EGFR mutation (exon 19Del mutation: n=135, L858R mutation: n=137) ,39 ALK translocation or undefined lung cancer patients. Sequential analyses were conducted to monitor CTC values during therapy and correlate radiological effects with treatment outcome.
Results:
There was no significant difference between CTC values and patients’ characristics including stage (P= 0.1015), EGFR mutation status(19 del:14.5 CTCs, L858R:12.6 CTCs, P=0.1868) , age (≤60 versus >60 years), gender, smoking status. Of 272 eligible and evaluable patients received EGFR-TKI, we found that patients harboring lower CTC levels (<20.5)were associated with longer PFS(432days, 95%CI:332.7-541.3) than those with higher CTC levels (≥20.5)(PFS: 308days, 95%CI:245.3-370.7;P=0.017). Patients with CTC <20.5 had a DCR of 77.11% compared with 58.49% in CTC >20.5 groups (P=0.008), patients with CTC <20.5 had a ORR of 51.20% compared with 33.96% in CTC >20.5 groups (P=0.029). Decreased CTC values correlated well with partial response after one month or three months’ treatment of EGFR-TKI (P=0.0082 and P=0.0023),but not with stable disease (P=0.1843 and P=0.8606).Multivariate analysis showed that CTC level was an independent prognostic factor for PFS (CTC level<20.5 vs ≥20.5,hazard ratio, 0.497; P=0.014).
Conclusion:
The change of CTCs correlated significantly with radiological response. This strategy may enable non-invasive, predictive and prognostic, specific biomarker in patients undergoing targeted therapies.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 4
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-075 - Addition of Bevacizumab for Malignant Pleural Effusion as the Manifestation of Acquired EGFR-TKI Resistance in NSCLC Patients (ID 4053)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
This study aimed to investigate the clinical value of bevacizumab in EGFR mutant non-small cell lung cancer (NSCLC) patients who had developed acquired resistance to EGFR-TKIs therapy that manifested as malignant pleural effusion (MPE).
Methods:
A total of 86 patients were included. Among them, 47 patients received bevacizumab plus continued EGFR-TKIs (B+T) and 39 patients received bevacizumab plus switched chemotherapy (B+C).
Results:
The curative efficacy rate for MPE in B+T group was significantly higher than that in B+C group (89.4% vs. 64.1%, P = 0.005). Patients in B+T group had longer progression-free survival (PFS) than those in B+C group (6.3 vs. 4.8 months, P = 0.042). While patients with acquired T790M mutation in B+T group had a significantly longer PFS than those in B+C group (6.9 vs. 4.6 months, P = 0.022), patients with negative T790M had similar PFS (6.1 vs. 5.5 months, P = 0.588). Overall survival (OS) was similar between two groups (P = 0.480). In multivariate analysis, curative efficacy was the independent prognostic factor for these patients (HR 0.275, P = 0.047). Figure 1 Figure 2
Conclusion:
B+T could be a valuable treatment for NSCLC patients presenting with MPE upon resistant to EGFR-TKIs therapy, especially for those with acquired T790M mutation.
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P3.02b-076 - Bisphosphonates Enhance Effect of EGFR-TKIs in NSCLC Patients with EGFR Mutation and Bone Metastases (ID 4817)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
Whether bisphosphonates could enhance the treatment outcome of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in non-small-cell lung cancer (NSCLC) patients with EGFR mutation and bone metastases (BM) remains controversial.
Methods:
251 NSCLC patients with EGFR mutation and BM were identified. As first-line treatment, 44 patients received EGFR-TKIs alone and 56 patients received EGFR-TKIs plus bisphosphonates therapy.
Results:
Comparing to TKIs alone, EGFR-TKIs plus bisphosphonates had significant longer progression-free survival (PFS: 11.5 vs 10.5 months; HR = 0.64, P = 0.030), but similar overall survival (OS: 20.2 vs 20.8 months; HR = 0.95, P = 0.847) in NSCLC with EGFR mutation and BM. Although the incidence of skeletal-related events in combined treatment group was lower than that in EGFR-TKIs alone group, there is no statistical significance (32.1% vs. 45.5%, P = 0.173). Chemotherapy plus bisphosphonates had similar PFS (6.4 VS 6.7 months; HR = 1.09, P = 0.684) and OS (15.5 vs 14.1 months; HR = 0.87, P = 0.486) to chemotherapy alone in patients with EGFR of wild type. In multivariate analysis, EGFR mutation was found to be a significant independent prognostic factor for OS in NSCLC patients with BM (HR = 0.722, P = 0.019). Figure 1
Conclusion:
The addition of bisphosphonates to EGFR-TKIs could enhance the effect of EGFR-TKIs in NSCLC patients with EGFR mutation and BM. Bisphosphonates did not bring additional benefit to chemotherapy in BM patients with EGFR of wild type. EGFR mutation was the significant independent prognostic factor for OS in NSCLC patients with BM.
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P3.02b-091 - Liver Metastases Is the Negative Predictive Factor for First-Line EGFR TKIs Therapy in NSCLC Patients with EGFR Mutation (ID 4054)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
Whether liver metastases (LM) could predict the treatment outcome of patients with non-small-cell lung cancer (NSCLC) and epidermal growth factor receptor (EGFR) mutation receiving first-line EGFR tyrosine kinase inhibitors (TKIs) remains controversial.
Methods:
A total of 598 patients with advanced NSCLC receiving EGFR detection were included. 99 NSCLC patients had LM and 56 of them with EGFR mutation received EGFR-TKIs as first-line therapy.
Results:
In EGFR mutation group, patients with LM had shorter progression-free survival (PFS: 7.4 vs. 11.8 months, P = 0.0002) and overall survival (OS: 20.8 vs. 31.5 months, P = 0.0057) compared to patients without LM when they received first-line EGFR-TKIs therapy. EGFR-mutated patients with LM received first-line chemotherapy had similar PFS and OS to patients without LM (PFS, 4.7 vs. 5.9 months, P = 0.3051; OS, 12.7 vs. 14.5 months, P = 0.3783). In EGFR wild type group, PFS and OS were also similar in patients with LM vs. without LM (PFS, 6.3 vs. 5.1 months, P = 0.2092; OS, 12.6 vs. 16.2 months, P = 0.4885). Univariate cox regression analyses identified only never smoking (HR = 0.536, P = 0.012) were significantly associated with better OS in NSCLC patients with LM. Figure 1
Conclusion:
Liver metastases is not only the negative predictive factor for first-line EGFR-TKIs therapy in NSCLC patients with EGFR mutation but also predicts poor effect of chemotherapy in NSCLC patients with EGFR wild type.
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P3.02b-104 - Rebiopsy for Patients with Non-Small-Cell Lung Cancer after Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Failure (ID 5808)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
All non-small cell lung cancer patients (NSCLC) with mutant epidermal growth factor receptor (EGFR) eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Rebiopsy and retesting plays more important role in clinical application for exploring resistant mechanisms and determining further therapy strategies. This retrospective study was be performed to determine the percentage of patients who underwent rebiopsy and retesting, and the rebiopsy and retesting effect on clinical strategies and patients prognosis.
Methods:
From October 2011 to March 2016, patients with advanced NSCLC who developed resistance to EGFR-TKIs were included into this study. EGFR mutation detection were performed by ARMS PCR in our institution.
Results:
A total of 539 patients were enrolled in this study with a median progression-free survival time (PFS) of 11.1 months according to RECIST criteria. In all, 297 (55.1%) patients underwent rebiopsy for 178 computed tomography (CT)-guided needle biopsies, 87 serous cavity effusion (including 80 pleural effusion, 3 ascitic fluid and 4 pericardial effusion), 21 superficial lymph node biopsy, 11 other procedures. 354 (65.7%) patients after EGFR-TKIs failure were performed EGFR mutation testing used by 288 rebiopsy and 66 plasma samples. 181 (51.5%) had T790M mutation. In 66 plasma samples, 29 (43.9%) hardored T790M mutation, 23 (34.8%) with mutation in accordance with before EGFR-TKIs treatment, 14 with wild-type EGFR. In all patients, 341 recieved further treatment in our hospital; 236 (69.2%) patients treated with chemotherapy, 43 (12.6%) recieved TKI combined local treatment, 42 (12.3%) changed second or third generation TKIs, 30 switched to other treament. But this part of data still underdone.
Conclusion:
Rebiopsy is feasible in patients after EGFR-TKIs failure. Rebiopsy could effect on further treatment strategies after especially third generarion EGFR-TKI in clinical application. While plasma is also an available surrogate of EGFR mutation testing for patients without suitable lesions for rebiopsy after disease progression.
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P3.02c - Poster Session with Presenters Present (ID 472)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02c-049 - Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrate Enhanced Antitumor Effect against Lung Cancer (ID 4411)
14:30 - 15:45 | Author(s): T. Jiang
- Abstract
Background:
Immunotherapy involving dendritic cells (DCs) vaccine has the potential to overcome the bottleneck of cancer therapy.
Methods:
Here, we engineered Lewis Lung cancer cells (LLC) and bone marrow derived DCs to express tumor-associated antigen (TAA), ovalbumin (OVA) via lentiviral vector plasmid encoding OVA gene. We then tested the anti-tumor effect of modified DCs both in vitro and in vivo.
Results:
The results demonstrated that in vitro modified DCs could dramatically enhance T cells proliferation (P < 0.01) and kill LLC significantly than control groups (P < 0.05). Moreover, modified DCs can reduce tumor size and prolong the survival of tumor-bearing mice than control groups (P < 0.01, P < 0.01; respectively). Modified DCs enhanced homing to T-cell-rich compartments and triggered naïve T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice (P < 0.05), suggesting the potential role of eliminating cancer stem-like cells in vivo. Figure 1
Conclusion:
These findings indicated that DCs bioengineered with TAA may enhance antitumor effect against murine lung cancer through novel mechanism that is worth further exploration.
