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Z. Dong



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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-027 - Combination of Biomarker and Clinicopathologic Characters May Circle out Beneficiaries through Second-Line Immunotherapy: A Meta Analyse (ID 8265)

      09:30 - 16:00  |  Author(s): Z. Dong

      • Abstract
      • Slides

      Background:
      Programmed cell death ligand 1 (PD-L1) expression had been proposed as predictive biomarker to immune-checkpoint inhibitors. Yet treatment responses are not always consistent with this single agent in the second-line therapy of NSCLC. Whether combination of PD-L1 and clinicopathologic characters could circle out optimal beneficiaries are still unknown.

      Method:
      We performed a meta-analysis of randomized control trials that compared immune-checkpoint inhibitors against chemotherapy in second-line therapy. Data including smoking status, EGFR status, KRAS status and histology were extracted as subgroup analyse to estimate the potential predictor of efficacy for anti PD-1/L1.

      Result:
      Five clinical trials that compared immune-checkpoint inhibitors against chemotherapy for second-line therapy were included. Both PD-L1 positive (HR=0.64, 95%CI=0.56-0.73, P<0.00001) and PD-L1 negative (HR=0.88, 95%CI=0.78-1.00, P=0.05) favored anti PD-1/L1. Subgroup analyse indicated that adenocarcinoma (ADC) as well as squamous cell carcinoma (SCC) preferred anti PD-1/L1. Never smokers may not benefit from anti PD-1/L1 but current/ever smokers did (HR=0.70, 95%CI=0.63-0.79, P<0.00001). Patients with EGFR mutation could not gain benefit from anti PD-1/L1 while the EGFR wild type could (HR=0.67, 95%CI=0.60-0.76, P<0.00001). Both KRAS mutation (HR=0.60, 95%CI=0.39-0.92, P=0.02) and wild type/unknown (HR=0.81, 95%CI=0.67-0.97, P=0.02) were apt to anti PD-1/L1. Figure 1



      Conclusion:
      Regardless of PD-L1 status, immune-checkpoint inhibitors could achieve better efficacy than chemotherapy in second-line therapy. Current/ever smokers without EGFR mutations may benefit more from anti PD-1/L1. Combination of PD-L1 and strongly relevant clinicopathologic characters should be considered to tailor optimal patients for anti PD-1/L1.

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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-042 - PD-L1 and CD8 Expression in EGFR-Mutant or ALK-Rearranged Patients with Lung Cancer (ID 10407)

      09:30 - 16:00  |  Author(s): Z. Dong

      • Abstract
      • Slides

      Background:
      Several studies indicate no response to check-point inhibitors on non-small-cell lung cancer with either EGFR-mutant or ALK-rearranged patients,of whom majority of international clinical trials involving PD-1/L1 inhibitors excluded. No solid evidences to interpret the underlying mechanism of poor clinical benefit to patients through PD-1/L1 inhibitors with driver genes mutation.

      Method:
      From 2010 to 2016, 482 patients and 263 patients with clinically operable lung cancer and advanced lung cancer respectively were collected at Guangdong Lung Cancer Institute (GLCI). All patients have detected for EGFR as well as ALK status. CD8 and PD-L1 expression was scored by immunohistochemistry with SP142 antibody. Five years survival rate was also analyzed.

      Result:
      Patients were assigned to EGFR/ALK positive group (344 cases) or negative group (401 cases). EGFR/ALK positive group contains 5.52% PD-L1+/CD8+; 11.92% PD-L1-/CD8+; 18.90% PD-L1+/CD8- and 63.66% PD-L1-/CD8-. EGFR&ALK negative group contains 13.97% PD-L1+/CD8+; 6.98% PD-L1-/CD8+; 30.42% PD-L1+/CD8- and 48.63% PD-L1-/CD8-. In EGFR/ALK positive group, PD-L1+/CD8+ is lower but PD-L1-/CD8- is higher than that of EGFR&ALK negative group (P<0.001). Significant statistical differences of 5 years survival rate were observed between four subgroups in EGFR/ALK positive group (PD-L1+/CD8+:41.9%, PD-L1-/CD8+: 91.0%, PD-L1+/CD8-: 75.4%, PD-L1-/CD8-: 69.7%; P=0.003). And there were no survival differences in EGFR&ALK negative group((PD-L1+/CD8+: 66.5%, PD-L1-/CD8+: 76.9%, PD-L1+/CD8-: 62.3%, PD-L1-/CD8-: 70.6%; P=0.341).

      Conclusion:
      Immunotherapy with PD-1/L1 inhibitors may not be suitable for EGFR-mutant or ALK-rearranged lung cancer patients with little co-expression of PD-L1 and CD8. However, these patients with such diver genes mutation reveal the best survival in PD-L1-/CD8+ subgroup and the worst survival in PD-L1+/CD8+ subgroup. Figure 1



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