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kenta Murotani
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-14 - Early Changes in Plasma CXCL2 and MMP2 Levels Predicts the Response to Anti-PD-1 Therapy in Non-Small-Cell Lung Cancer (ID 1675)
09:45 - 18:00 | Author(s): kenta Murotani
- Abstract
Background
Previously we reported that changes in the plasma levels of CXCL2 and MMP2, measured by a bead-based multiplex assay: Bio-Plex 200 system, were significantly associated with the clinical outcomes of anti-PD-1 therapy (Matsuo, et al. IJC. 2018). Here we attempted to validate CXCL2 and MMP2, measured by ELISA, as a marker of the effectiveness of anti-PD-1 therapy in expanded patient cohort.
Method
Peripheral blood samples were taken from 97 patients with non-small cell lung cancer before nivolumab or pembrolizumab treatment and after 4-10 weeks from the patients who continued these drugs. The levels of CXCL2 and MMP2 were examined before and after anti-PD-1 therapy. We employed Cox regression analysis for CXCL2 and MMP2 as a single explanatory carriable. In comparing the fitness of CXCL2 and MMP2 Cox models, discrimination was assessed by the Harrell’s C-statistic for survival data. Bootstrap methods with 10000 resamplings were used to assess the stability of the regression analysis predictors. The optimal cutoff point was determined as the point at which the Youden index was maximized by ROC curve. Survival curves were generated using the Kaplan–Meier method and comparisons made using the log-rank test.
Result
The changes in the plasma levels of CXCL2 after treatment were significantly correlated with PFS (HR 1.003, 95%CI: 1-1.005, P=0.026) and OS (HR 1.004, 95%CI: 1.001-1.007, P=0.003). The C-statistic of the CXCL2 model for PFS and OS were 0.652 (95% CI: 0.437-0.727) and 0.626 (95% CI: 0.528-0.722), respectively. The decreasing revels of CXCL2 tended to be related to better DCR (P=0.134). The changes in the plasma levels of CXCL2 < 29.1 pg/ml was associated with better PFS (HR 2.872, 95%CI: 1.785-4.618, P<0.001) and OS (HR 2.800, 95%CI: 1.633-4.801, P<0.001). The changes in the plasma levels of MMP2 after treatment were also significantly correlated with PFS (HR 0.998, 95%CI: 0.996-0.999, P=0.003) and OS (HR 0.998, 95%CI: 0.996-0.999, P=0.001). The C-statistic of the MMP2 model for PFS and OS were 0.599 (95% CI: 0.515-0.673) and 0.614 (95% CI: 0.523-0.703). The increasing revels of MMP2 was significantly related to better DCR (P=0.020). The changes in the plasma levels of MMP2 > 0.847 ng/ml was associated with better PFS (HR 0.614, 95%CI: 0.388-0.971, P=0.037) and OS (HR 0.501, 95%CI: 0.295-0.852, P=0.011).
Conclusion
The early change of CXCL2 and MMP2 were significantly associated with the clinical outcomes of anti-PD-1 therapy. Since these factors in plasma can be easily measured by minimally invasive method, they could be clinically applicable as biomarkers for predicting the clinical benefit of anti-PD-1 therapy for NSCLC patients.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-01 - Changes of BCR Repertoire Are Predictive Biomarker for the Efficacy of Immune Checkpoint Inhibitor in NSCLC (ID 1688)
10:15 - 18:15 | Author(s): kenta Murotani
- Abstract
Background
Clonal diversity of T cell receptor (TCR) and/or B cell receptor (BCR) repertoires might play a major role in antitumor immunity in cancer patients. Assessment of TCR and BCR repertoires might enable us to predict the efficacy of immune checkpoint inhibitors (ICI).
Method
The study population comprised 30 patients with non-small-cell lung cancer (NSCLC), who started treatment with nivolumab (3mg/kg, every two weeks) or pembrolizumab (200mg, every three weeks) between February 2016 and August 2017. Patient blood samples were collected before and four to six weeks after the initiation of treatment. TCR and BCR chain sequences were determined by using the unbiased gene amplification method with Adaptor-Ligation PCR. The diversity of TCR and BCR repertoires was evaluated with inverse Shannon-Weaver index (iSWI).
Result
We compared the iSWI between before and after treatment. The fold changes of iSWI in BCR repertoire after treatment in patients with PR were significantly higher than those with SD or PD. In contrast, the fold changes of iSWI in TCR repertoire after treatment were not associated with tumor responses. When the cut-off value of fold change of iSWI in BCR repertoire after treatment was determined as 0.85, 25 (83%) and 5 (17%) patients were considered as high and low fold change group, respectively. Progression free survival in the high fold change group was significantly longer compared with that in the low fold change group (182 vs 49 days; 95% confidence interval (CI);99-N.R. vs 31-168 days, respectively; P=0.01).
Conclusion
Our findings suggest that reduced repertoire diversity in BCR, but not in TCR, might be associated with better clinical outcomes in advanced NSCLC patients treated with ICI. Assessment of the changes of BCR repertoire after treatment might be useful for predicting the efficacy of ICI. The present results require confirmation in a large-scale prospective study.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-11 - Retreatment with EGFR-TKI for 541 NSCLC Patients with EGFR Mutation (ID 2633)
10:15 - 18:15 | Author(s): kenta Murotani
- Abstract
Background
Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) is remarkably effective against non-small cell lung cancer (NSCLC) harboring EGFR activating mutation. However, tumors almost inevitably develop resistance approximately after one year of EGFR-TKI treatment. In addition, some patients can not tolerate an EGFR-TKI treatment because of adverse events and result in discontinuation of the treatment. In such cases, the same or other EGFR-TKI may be re-administered. However, its efficacy is not fully evaluated.
Method
We retrospectively investigated patients who received EGFR-TKI between January 2008 and August 2017. Among these patients, the response rate and time to treatment failure (TTF) for each re-administered TKI were assessed. We assessed each TTF for patients who discontinued the prior EGFR-TKI because of progressive disease (PD group) and patients who discontinued TKI because of adverse events (AE group). We also evaluated the overall survival (OS) for the patients who received the retreatment with EGFR-TKI and who did not.
Result
A total of 1400 patients from 11 institutions were enrolled in this study. Among them, 570 patients received retreatment with EGFR-TKI, and 541 were eligible. Among the 395 patients who discontinued prior EGFR-TKI because of disease progression, the response rate and the median TTF of subsequent Gefitinib/Erlotinib/Afatinib were 8%/8%/18%, and 4.9/3.2/4.3 months, respectively. The median TTF for the AE group was significantly longer than that for the PD group (10.8 months vs 3.8 months, p<0.0001). In the AE group, The OS for patients receiving retreatment with EGFR-TKI was significantly better than the OS for patients without retreatment (Hazard Ratio = 0.256, p < 0.0001). Similarly, in the PD group, the OS for patients receiving retreatment with EGFR-TKI was significantly better than the OS for patients without retreatment (Hazard Ratio = 0.456, p < 0.0001).
Conclusion
Retreatment with EGFR-TKI was shown to be effective for both patients who discontinued prior EGFR-TKI because of disease progression as well as adverse events.
