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Tomohiro Ozaki

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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): Tomohiro Ozaki

      • Abstract
      • Presentation
      • Slides


      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.


      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.


      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).


      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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