Optimal Therapeutic Strategy for PD-L1 Negative Metastatic Non-Small Cell Lung Cancer: A Decision-Making Guide Based
Mariana Malvicini1, Maysa Silveira Vilbert2, José N Minatta3
1Cancer Immunobiology Laboratory, Instituto de Investigaciones en Medicina Traslacional, Universidad Austral-Consejo Nacional de Investigaciones Cientificas y Tecnologicas (CONICET), Buenos Aires, Argentina.
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.
Insights
Immune checkpoint inhibitors (ICIs) offer new lung cancer treatments. This guide helps clinicians choose optimal therapies for non-small cell lung cancer (NSCLC) patients with PD-L1-negative tumors.
Area of Science:
- Oncology
- Immunotherapy
- Cancer Research
Background:
- Immune checkpoint inhibitors (ICIs) have transformed lung cancer treatment by enhancing antitumor immune responses.
- ICIs function by blocking regulatory cell surface molecules like CTLA-4, PD-1, and PD-L1 using specific antibodies.
- Anti-PD-1 therapies have shown significant long-term survival benefits and durable responses in non-small cell lung cancer (NSCLC) patients.
Purpose of the Study:
- To address the undefined optimal treatment approach for patients with PD-L1-negative NSCLC.
- To provide a clinical decision-making guide for managing PD-L1-negative NSCLC.
- To synthesize the latest data on treatments, prognostic factors, predictive biomarkers, and real-world evidence for this patient group.
Main Methods:
- Review of recent clinical trial data on ICI efficacy in NSCLC.
- Analysis of prognostic factors and predictive biomarkers relevant to PD-L1-negative NSCLC.
- Incorporation of real-world evidence for treatment strategies.
Main Results:
- Combination therapy with anti-PD1/PD-L1 and platinum chemotherapy improves survival outcomes compared to chemotherapy alone, irrespective of PD-L1 expression.
- While high PD-L1 expression shows promising results with ICIs, optimal strategies for PD-L1-negative NSCLC require further definition.
- Evidence suggests a need for tailored therapeutic approaches based on individual patient data.
Conclusions:
- Optimal treatment strategies for PD-L1-negative NSCLC are still evolving.
- A comprehensive guide integrating current data is proposed to aid clinicians in therapeutic decision-making.
- Further research and real-world data are crucial for refining treatment protocols for PD-L1-negative NSCLC.
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