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PD-1/PD-L1 checkpoint blockades in non-small cell lung cancer: New development and challenges
Xiangjiao Meng1, Yanli Liu2, Jianjun Zhang3
1Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academic of Medical Science, Jinan, 250117, China.
Abstract:
PD-1/PD-L1 checkpoint blockades have dramatically changed the landscape for second-line treatment of non-small cell lung cancer (NSCLC). Based on the promising results of Keynote-024 presented so far, pembrolizumab has been approved as first-line treatment for advanced PD-L1 positive NSCLC patients. However, overall response rate (ORR) is limited to PD-1/PD-L1 checkpoint blockades when used as single agent. Combining with chemotherapy, anti-CTLA-4 antibodies, targeted therapy, radiotherapy or other treatment options is perceived as an appealing method aimed at achieving higher efficacy. There are many clinical trials on going or finished assessing the efficacy and safety of the PD-1/PD-L1 blockades alone or combining with other approaches in first-line or second-line treatments. A lot of challenges need to be overcome before PD-1/PD-L1 checkpoint blockades are widely used in the patients with NSCLC including the identification of optimal combination, treatment-related adverse effects, the high cost and lack of effective predictive markers. In this review, we focus on outlining current clinical trials and challenges for future research of PD-1/PD-L1 pathway checkpoint blockades in NSCLC.
Insights
Programmed cell death protein 1 (PD-1)/PD-L1 checkpoint inhibitors show promise for non-small cell lung cancer (NSCLC). Combinations with other therapies are being explored to improve response rates, despite challenges in optimal use and predictive markers.
Area of Science:
- Immunotherapy
- Oncology
- Pharmacology
Background:
- Programmed cell death protein 1 (PD-1)/PD-L1 checkpoint blockade has transformed non-small cell lung cancer (NSCLC) treatment, particularly in second-line settings.
- Pembrolizumab is approved for first-line treatment in advanced, PD-L1 positive NSCLC based on positive trial data.
Purpose of the Study:
- To review current clinical trials assessing PD-1/PD-L1 checkpoint inhibitors in NSCLC.
- To outline challenges and future research directions for PD-1/PD-L1 pathway inhibitors in NSCLC treatment.
Main Methods:
- Review of ongoing and completed clinical trials evaluating PD-1/PD-L1 inhibitors.
- Analysis of combination strategies including chemotherapy, anti-CTLA-4 antibodies, targeted therapy, and radiotherapy.
- Assessment of efficacy and safety data for single-agent and combination therapies.
Main Results:
- Single-agent PD-1/PD-L1 blockade shows limited overall response rates (ORR) in NSCLC.
- Combination therapies are being investigated to enhance efficacy in first-line and second-line NSCLC treatments.
- Numerous clinical trials are evaluating these approaches.
Conclusions:
- Significant challenges remain for widespread PD-1/PD-L1 inhibitor use in NSCLC.
- Key challenges include identifying optimal combinations, managing treatment-related adverse effects, addressing high costs, and developing effective predictive biomarkers.
- Further research is crucial to overcome these hurdles and optimize PD-1/PD-L1 pathway blockade in NSCLC management.
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