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Optimal Therapeutic Strategy for PD-L1 Negative Metastatic Non-Small Cell Lung Cancer: A Decision-Making Guide Based on Clinicopathological and Molecular Features

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Opinion Statement

Strategies using immune checkpoint inhibitors (ICI), which can enhance antitumor immune responses, have revolutionized the lung cancer therapeutic landscape. The ICI mechanism of action involves the blockade of regulatory cell surface molecules using antibodies against the Cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) (ipilimumab, tremelimumab); the programmed death receptor-1 (PD-1; nivolumab, pembrolizumab); or the PD ligand-1 (PD-L1; atezolizumab, durvalumab). Notably, anti-PD-1 demonstrated long-term survival benefits, durable objective responses, and a manageable safety profile in patients with non-small cell lung cancer (NSCLC). The combination of anti-PD1 or anti-PD-L1 and platinum chemotherapy achieved better survival outcomes than chemotherapy alone, which was observed irrespective of PD-L1 expression on cancer cells. Although promising results have been reported from large clinical trials, especially for patients with high PD-L1 expression, the optimal treatment approach for patients with PD-L1-negative NSCLC has yet to be defined. We propose a guide for clinicians in the therapeutic decision-making process based on the latest data available about treatments, prognostic factors, predictive biomarkers, and real-world evidence in PD-L1-negative NSCLC patients.

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Authors and Affiliations

  1. Cancer Immunobiology Laboratory, Instituto de Investigaciones en Medicina Traslacional, Universidad Austral-Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires, Argentina

    Mariana Malvicini PhD & Manglio M. Rizzo MD, PhD

  2. Princess Margaret Cancer Center, University of Toronto, Toronto, Canada

    Maysa Silveira Vilbert MD

  3. Clinical Oncology Unit, Hospital Universitario Austral, Av. Presidente Perón 1500, (B1629ODT) Derqui-Pilar, Buenos Aires, Argentina

    José N. Minatta MD & Manglio M. Rizzo MD, PhD

  4. Departamento de Oncología Médica, Oncosalud – AUNA, Lima, Perú

    Valeria Colomo Costas MD

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Malvicini, M., Vilbert, M.S., Minatta, J.N. et al. Optimal Therapeutic Strategy for PD-L1 Negative Metastatic Non-Small Cell Lung Cancer: A Decision-Making Guide Based on Clinicopathological and Molecular Features. Curr. Treat. Options in Oncol. 24, 1550–1567 (2023). https://doi.org/10.1007/s11864-023-01132-w

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