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Norikazu Matsuo
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P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.01-04 - A Phase II Trial of Weekly Nab-Paclitaxel in the Salvage Setting for Advanced Non-Small Cell Lung Cancer: Results of NICE Salvage Study (ID 1534)
09:45 - 18:00 | Author(s): Norikazu Matsuo
- Abstract
Background
The optimal treatment in patients with advanced non-small cell lung cancer (NSCLC) after failing second- or third-line chemotherapy, i.e. NSCLC in salvage setting, has yet to be established. A small study reported that solvent-based paclitaxel (sb-P) monotherapy was safe and efficacious and could be a treatment option for NSCLC in salvage setting (Anticancer Res 2005). Nanoparticle albumin-bound paclitaxel (nab-P) showed a higher overall response rate (ORR) and better tolerability than sb-P when combined with carboplatin (CBDCA) as a first-line chemotherapy (J Clin Oncol 2012). These results suggest that nab-P monotherapy could be better therapeutic option than sb-P monotherapy for NSCLC in salvage setting. We therefore planned NICE Salvage study aiming to assess the efficacy and safety of nab-P monotherapy for NSCLC patients in salvage setting.
Method
NICE Salvage study was a multicenter single arm phase II study. Eligibility criteria included patients aged >= 20 years, with PS 0-2 and adequate organ function, and who have failed two or three prior lines of chemotherapy including at least a platinum-containing regimen for pathologically-proven advanced NSCLC. Patients who had treatment history with sb-P or nab-P, or had tumors harboring EGFR mutation or ALK fusion gene were excluded. Nab-P was administered at a dose of 80 mg/m2 on days 1,8 and 15 of a 28-days cycle and repeated until progressive disease, unacceptable toxicity, or patient’s refusal. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), ORR, disease control rate (DCR), efficacy according to prior use of docetaxel, quality of life, and safety. The study is powered to detect a 1.5-month improvement in median PFS in the investigational arm beyond the 2.0-month median PFS estimated from historical data. Assuming a one-sided 0.10 level of Type I error and 80% power, target sample size is calculated at 35. (UMIN000016173).
Result
Thirty-eight patients were enrolled and a patient was excluded from efficacy and safety analysis. Patient’s characteristics (n = 38) were as follows: median age = 68 years, male/female = 31/7, adenocarcinoma/squamous cell carcinoma /others = 20/15/3. Median PFS and OS was 3.5 month (95% confidence interval (CI), 1.7-3.8), and 13.4 month (95%CI, 9.1-25.1), respectively. ORR and DCR were 10.8% (95%CI, 2.9-24.8 ) and 56.8% (95%CI, 38.3-71.3 ), respectively. Grade 3 or 4 treatment-related adverse events were neutropenia (10.8%), anemia (2.7%), hepatotoxicity (2.7%) and diarrhea (2.7%). One treatment-related death (pulmonary infection) was observed.
Conclusion
This study failed to meet predefined primary endpoint. However the results showed that nab-P monotherapy was moderately efficacious and well-tolerated, suggesting the need for further investigation for NSCLC in salvage setting.
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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 | Presenting Author(s): Norikazu Matsuo
- 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: 2
- 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): Norikazu Matsuo
- 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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P2.04-85 - Clinical Significance of the PD-L2 Expression in Patients with NSCLC Receiving Anti-PD-1 Inhibitors (ID 1611)
10:15 - 18:15 | Author(s): Norikazu Matsuo
- Abstract
Background
The programmed cell death 1 (PD-1) receptor–ligand interaction is a major pathway often hijacked by tumors to suppress immune control. Programmed cell death-ligand 1 (PD-L1), a ligand of PD-1, can potentially predict the response to anti-PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC); however, the role of PD-L2, another ligand of PD-1, remains unclear in patients receiving anti-PD-1 inhibitors. This retrospective study aims to determine the significance of the PD-L2 expression in anti-PD-1 inhibitors–treated patients with NSCLC.
Method
We enrolled 82 patients with advanced or recurrent NSCLC who received anti-PD-1 inhibitors. The PD-L2 expression was assessed by immunohistochemical analysis staining with an antibody of PD-L2 (1:200, clone 176611), and cases with >1% tumor staining of PD-L2 were considered positive. Furthermore, we analyzed correlations between PD-L2 expression and patients’ characteristics, efficacy, and immune-related adverse events (irAEs) of anti-PD-1 inhibitors.
Result
In this study, 59 (72.0%) and 56 (68.3) patients with NSCLC exhibited positive tumor PD-L2 and PD-L1 staining, respectively. Overall, 39 irAEs developed in 36 patients. The PD-L2 expression markedly correlated with the development of irAEs; however, we observed no correlation between PD-L2 expression and the efficacy of anti-PD-1 inhibitors. Other factors, including the PD-L1 expression, age, sex, smoking status, histology, did not correlate with the development of irAEs.
Conclusion
This study suggests that the PD-L2 expression could be accountable for the development of irAEs in anti-PD-1 inhibitors–treated patients with NSCLC.
