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Kouzo Yamada
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EP1.01 - Advanced NSCLC (ID 150)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.01-72 - Treatment Outcome of 2nd Generation EGFR-TKI for Non-Small Cell Lung Cancer (Now Available) (ID 1988)
08:00 - 18:00 | Author(s): Kouzo Yamada
- Abstract
Background
Efficacy of EGFR-TKI has been demonstrated in 1st line treatment for EGFR mutation positive NSCLC. Afatinib, 2nd generation EGFR-TKI inhibits HER2 (ErbB2) or ErbB4 in addition to the EGFR (ErbB1), is expected more effective compared to the 1st generation EGFR-TKI. In this study, we investigated retrospectively on the treatment outcome of the cases that received 2nd generation EGFR-TKI treatment at our institution.
Method
The subjects were 70 patients treated with a 2nd generation EGFR-TKI afatinib for the period from May 2014 to April 2018. Age, gender, smoking history, performance status (ECOG), EGFR mutation type, starting dose, dose reduction during treatment period, objective response, presence of brain metastasis, EGFR-TKI treatment line and T790M mutation result were retrospectively analyzed the association with the time to treatment failure and survival.
Result
Among the 70 patients, male 28 cases and female 42 cases, and 42 never smoker included. Median age was 65 years old (43-88 years old). EGFR mutation type included exon 19 deletion 42 cases, exon 21 L858R 13 cases, uncommon mutation 13 cases and compound mutation 2 cases. 18 cases were administered with 40mg initial dose, 28 cases were 30mg and 24 cases were 20mg. 68 cases were good performance status (0 or 1), and 33 (47%) cases had brain metastasis. Dose reduction were performed in 43 (61%) cases, and partial response were observed in 34 (49%) cases. 36 (51%) cases were no pretreatment with EGFR-TKI (afatinib as first EGFR-TKI). Of the 70 cases, 33 (47%) cases were performed re-biopsy, and 15 cases of those were proved T790M acquired resistant mutation.
Conclusion
Good performance status, dose reduction, good objective response, no brain metastasis, early EGFR-TKI treatment line and T790M mutation positivity were significantly associated with prolongation of the time to treatment failure, but no significant characteristics were associated with prolongation of the survival.
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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): Kouzo Yamada
- 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.
