The latest clinical trials of lung cancer immunotherapies: a review of literature

Lung cancer remains a leading cause of cancer-related mortality worldwide. While chemotherapy has been the mainstay treatment, the emergence of immune checkpoint inhibitors (ICIs) targeting programmed death ۱ (PD-۱) and programmed death-ligand ۱ (PD-L۱) has revolutionized the management of non-small cell lung cancer (NSCLC). This narrative review aims to provide an update on the latest findings from clinical trials evaluating immunotherapies, particularly focusing on PD-۱/PD-L۱ inhibitors in various lung cancer treatment settings. Methods: A comprehensive literature search was conducted to identify the most promising clinical trials assessing the efficacy of PD-۱/PD-L۱ inhibitors, including nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab, in lung cancer. The trials were evaluated based on their study design, patient population, and treatment outcomes. Results: PD-۱/PD-L۱ inhibitors have demonstrated significant anti-tumor activity in NSCLC, with some agents receiving FDA approval for first-line, second-line, and adjuvant therapy settings. A comprehensive analysis of ۱۱ clinical trials revealed that higher levels of PD-L۱ expression correlate with better responses to these inhibitors in both first-line and second-line therapies. Pembrolizumab has emerged as a highly effective first-line treatment for advanced NSCLC, particularly in patients exhibiting high PD-L۱ expression. In a pivotal phase III trial, pembrolizumab monotherapy significantly outperformed chemotherapy, yielding a median overall survival (OS) of ۳۰ months for patients with PD-L۱ expression of ۵۰% or greater, compared to ۱۴.۲ months for those receiving chemotherapy. For patients with PD-L۱ expression of at least ۱%, the median OS was ۱۶.۷ months versus ۱۲.۱ months for chemotherapy. Atezolizumab, recognized as the first anti-PD-L۱ antibody approved for NSCLC, has demonstrated both efficacy and safety as a second-line treatment option for advanced squamous and adenocarcinoma histologies. In a phase III trial, atezolizumab provided a median OS of ۱۳.۸ months, significantly better than the ۹.۶ months observed with docetaxel in previously treated NSCLC patients. Furthermore, combination therapies involving PD-۱/PD-L۱ inhibitors and chemotherapy have demonstrated promising results in improving survival rates. A meta-analysis revealed that the concurrent use of chemotherapy with PD-۱/PD-L۱ inhibitors, including pembrolizumab and atezolizumab, exhibited enhanced efficacy compared to chemotherapy alone in the first-line treatment of non-small cell lung cancer (NSCLC). Conclusion: While chemotherapy remains the current standard of care for lung cancer, the approval of specific ICI therapies for select lung cancer subtypes highlights the potential of these agents in becoming a cornerstone of standard care. However, overcoming challenges associated with ICI therapy, such as patient selection, biomarker identification, and management of immune-related adverse events, is crucial for optimizing their clinical benefit.

کلیدواژه ها:

lung cancer ، immunotherapy ، clinical trial ، immune checkpoint inhibitors