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Motoyasu Okuno



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    MA03 - Clinomics and Genomics (ID 119)

    • Event: WCLC 2019
    • Type: Mini Oral Session
    • Track: Advanced NSCLC
    • Presentations: 1
    • Now Available
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      MA03.11 - Chemotherapy After PD-1 Inhibitors Versus Chemotherapy Alone in Patients with Non–Small Cell Lung Cancer (WJOG10217L) (Now Available) (ID 409)

      10:30 - 12:00  |  Author(s): Motoyasu Okuno

      • Abstract
      • Presentation
      • Slides

      Background

      Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response in patients with non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of subsequent chemotherapy after PD-1 inhibitors (CAP) compared with chemotherapy alone.

      Method

      We conducted a multicenter retrospective cohort study for patients with advanced or recurrent NSCLC who were treated at 47 institutions across Japan between 1 April 2014 and 31 July 2017 with chemotherapy (docetaxel with or without ramucirumab; S-1; or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort). The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors, including age, sex, smoking status, performance status, histology, EGFR or ALK genetic alterations, brain metastasis, and recurrence after curative radiotherapy.

      Result

      A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology, EGFR or ALK alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 10.8% for the control cohort (ORR ratio, 1.75; 95% confidence interval [CI], 1.25–2.45; P = .001). Median PFS was 3.5 and 2.6 months for the CAP and control cohorts, respectively (hazard ratio [HR], 0.862; 95% CI, 0.743–0.998; P = .048). The PFS rate at 3, 6, and 12 months was 53.3%, 28.5%, and 4.6%, respectively, for the CAP cohort, and 44.3%, 19.7%, and 6.1% for the control cohort. Median OS was 9.8 months for the CAP cohort and 10.3 months for the control cohort (HR, 0.979; 95% CI, 0.813–1.179; P = .822).

      Conclusion

      After adjustment for selection bias using propensity score–weighted analysis, CAP showed a significantly higher ORR and longer PFS compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into an OS advantage, and no PFS benefit was apparent at 12 months despite the improvement observed at 3 and 6 months. Our findings suggest that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.

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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): Motoyasu Okuno

      • 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.