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Outstanding clinical efficacy of PD-1/PD-L1 inhibitors for pulmonary pleomorphic carcinoma

  • Jiyun Lee
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Yoon La Choi
    Affiliations
    Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Hyun Ae Jung
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Se-Hoon Lee
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Jin Seok Ahn
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Myung-Ju Ahn
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Keunchil Park
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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  • Jong-Mu Sun
    Correspondence
    Corresponding author: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. Fax: +82 2 3412 3996.
    Affiliations
    Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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      Highlights

      • Pulmonary pleomorphic carcinomas (PCs) are known to express a high level of PD-L1.
      • Given its poor prognosis, the role of PD-L1 in PCs warrants further investigation.
      • In this study, 89.6% were PD-L1 positive (≥1%) and 80.0% had high PD-L1 expression.
      • Immunotherapy showed ORR 49%, mPFS 7.2 months and mOS 22.2 months.
      • High PD-L1 expression group showed longer PFS (7.2 versus 1.5) and OS (22.2 versus 3.5).

      Abstract

      Background

      We evaluated programmed death ligand 1 (PD-L1) expression and efficacy of PD-1/PD-L1 inhibitors in patients with pulmonary pleomorphic carcinoma (PC).

      Methods

      We created two cohorts of patients diagnosed with pulmonary PC from 2016 to 2019, PD-L1 expression and programmed death 1 (PD-1)/PD-L1 inhibitor efficacy cohorts. The PD-L1 expression cohort included all patients evaluated for PD-L1 expression, irrespective of PD-1/PD-L1 inhibitor therapy. High PD-L1 expression was defined as ≥50% positive tumour cells (TC) for 22C3, ≥25% for SP263 or ≥10%/5% TC/immune cell (IC) for SP142. The PD-1/PD-L1 efficacy cohort included patients treated with PD-1/PD-L1 inhibitors, irrespective of PD-L1 tests.

      Results

      One hundred twenty-five of 175 patients diagnosed with pulmonary PCs were included in the PD-L1 expression cohort. Among them, 112 patients (89.6%) had PD-L1-positive (≥1%) tumours and 100 (80.0%) had tumours with high PD-L1 expression. A total of 49 patients were included in the efficacy cohort: 40 received pembrolizumab, 7 nivolumab and 2 atezolizumab. The objective response rate was 49.0%, with a median progression-free survival (PFS) of 7.2 months and a median overall survival of 22.2 months. In the efficacy cohort, high PD-L1 expression (n = 41) was associated with longer PFS (median: 7.2 versus 1.5 months, hazard ratio [HR]: 0.53 [0.22–1.29], p = 0.16) and overall survival (median: 22.2 versus 3.5, HR: 0.21 [0.08–0.57], p = 0.001) than low/negative/unknown PD-L1 expression (n = 8).

      Conclusion

      PD-1/PD-L1 inhibitors show outstanding efficacy for pulmonary PCs, and this is possibly attributable to high PD-L1 expression in these tumours.

      Keywords

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