Advances and challenges of first-line immunotherapy for non-small cell lung cancer: A review
Haiyang Guo1,2, Jun Zhang2,3, Chao Qin2,3
1Institute of Surgery, School of Medicine and Life Sciences, Chengdu University of TCM, Chengdu, China.
Abstract:
The current use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has dramatically changed the clinical strategy for metastatic non-small cell lung cancer (mNSCLC). As a result of great achievements in clinical trials, 6 programmed death-1 inhibitors (sintilimab, camrelizumab, tislelizumab, pembrolizumab, cemiplimab, and nivolumab), 2 programmed death-ligand 1 inhibitors (sugemalimab and atezolizumab), and 1 cytotoxic T lymphocyte-associated antigen-4 inhibitor (ipilimumab) have been approved as first-line treatment for mNSCLC by the US Food and Drug Administration. Recently, research on ICIs has shifted from a large number of second-line to first-line settings in clinical trials. Results from first-line trials have shown that almost all driver-negative mNSCLC are treated with ICIs and significantly prolong patient survival; however, the low response rate and adverse reactions to immunotherapy remain to be addressed. Here, we summarize the use of ICIs, including monotherapy and combination therapy, in the first-line treatment of mNSCLC in recent years and discuss the low response rate and adverse reactions of ICIs as well as the challenges and expectations for the first-line treatment of mNSCLC in the future.
Insights
Immune checkpoint inhibitors (ICIs) have transformed first-line treatment for metastatic non-small cell lung cancer (mNSCLC), improving survival. However, challenges like low response rates and side effects require further research for optimal immunotherapy strategies.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Immune checkpoint inhibitors (ICIs) have revolutionized metastatic non-small cell lung cancer (mNSCLC) treatment.
- Several programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors are now FDA-approved for first-line mNSCLC therapy.
- Clinical research has shifted focus from second-line to first-line ICI settings.
Approach:
- This review summarizes recent advances in first-line ICI monotherapy and combination therapy for mNSCLC.
- It analyzes the efficacy and safety profiles of approved ICI agents.
- The discussion includes current challenges and future directions in mNSCLC immunotherapy.
Key Points:
- First-line ICI treatment significantly prolongs survival in driver-negative mNSCLC patients.
- Despite advancements, low response rates and immunotherapy-related adverse events remain critical issues.
- Optimizing ICI efficacy and managing toxicity are key areas for future research.
Conclusions:
- ICIs represent a major breakthrough in first-line mNSCLC treatment, enhancing patient survival.
- Addressing the limitations of response rates and adverse reactions is crucial for further progress.
- Continued research into novel combinations and treatment strategies is expected to improve outcomes for mNSCLC patients.
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