Novel immunotherapy combinations in neoadjuvant non-small cell lung cancer (NSCLC): a better chance at cure?
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ABSTRACT:
SUBMITTER: Salter AI
PROVIDER: S-EPMC11002516 | biostudies-literature | 2024 Mar
REPOSITORIES: biostudies-literature
Publications
Novel immunotherapy combinations in neoadjuvant non-small cell lung cancer (NSCLC): a better chance at cure?
Salter Alexander I AI Das Millie M
Translational lung cancer research 20240315 3
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Project description:Immune checkpoint inhibitors (ICIs) have revolutionized the approach to advanced and locally advanced non-small-cell lung cancer (NSCLC). Antibodies blocking inhibitory immune checkpoints, such as programmed death 1 (PD-1) and its ligand (PD-L1), have remarkable antitumor efficacy and have been approved as a standard first- or second-line treatment in non-oncogene-addicted advanced NSCLC. The successful application of immunotherapy in advanced lung cancer has motivated researchers to further evaluate its clinical role as a neoadjuvant setting for resectable NSCLC and for improved long-term overall survival and curative rates. In this review, we discuss the efforts that incorporate ICIs into the treatment paradigm for surgically resectable lung cancer. We reviewed the early-phase results from neoadjuvant clinical trials, the landscape of the majority of ongoing phase III trials, and discuss the prospects of ICIs as a curative therapy for resectable lung cancer. We also summarized the potential biomarkers and beneficiaries involved in the current study, as well as the remaining unresolved challenges for neoadjuvant immunotherapy.
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Project description:Lung cancer is the malignant tumor with the highest morbidity and mortality in the world. In recent ten years, with the emergence of new drugs and the optimization of treatment mode, the treatment of lung cancer is entering an era of precision and individualization. Neoadjuvant therapy can reduce tumor size, degrade tumor stage, kill circulating tumor cells and micrometastases in the body, afford operation possibility, and benefit the long-term survival of patients. However, the traditional neoadjuvant chemotherapy combined with surgical treatment seems to have entered the bottleneck period of efficacy and is difficult to achieve breakthrough progress. At the same time, the amazing efficacy of immunotherapy is gradually innovating the treatment mode of lung cancer. In recent years, the research data of immune checkpoint inhibitors in the treatment of non-small cell lung cancer (NSCLC) shows an explosive growth. Immunotherapy has been applied to the first-line treatment of advanced NSCLC. Therefore, some clinical trials have applied immunotherapy to neoadjuvant treatment of resectable NSCLC patients. In this paper, the efficacy, possible mechanisms, potential risks and existing problems of neoadjuvant immunotherapy for resectable NSCLC patients are reviewed, and the future development direction of neoadjuvant immunotherapy is discussed.
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Project description:Immune checkpoint inhibitor (ICI) has been proven to be a major breakthrough in patients with advanced non-small cell lung cancer. Up to now, neoadjuvant therapy using ICI are rare. However, in the context of cancer immunotherapy, neoadjuvant treatment may offer an extra advantage. In this review, we will disscuss the existing preclinical data and emerging clinical findings in the neoadjuvant setting and its potential mechanism of action. We will also highlight the potential damage and the questions that are required to be answered.
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Project description:Early-stage NSCLC (stages I and II, and some IIIA diseases) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases, with surgery being its main treatment modality. The risk of disease recurrence and cancer-related death, however, remains high among NSCLC patients after complete surgical resection. In previous studies on the long-term follow-up of post-operative NSCLC, the results showed that the five-year survival rate was about 65% for stage IB and about 35% for stage IIIA diseases. Platinum-based chemotherapy with or without radiation therapy has been used as a neoadjuvant therapy or post-operative adjuvant therapy in NSCLC, but the improvement of survival is limited. Immune checkpoint inhibitors (ICIs) have effectively improved the 5-year survival of advanced NSCLC patients. Cancer vaccination has also been explored and used in the prevention of cancer or reducing disease recurrence in resected NSCLC. Here, we review studies that have focused on the use of immunotherapies (i.e., ICIs and vaccination) in surgically resectable NSCLC. We present the results of completed clinical trials that have used ICIs as neoadjuvant therapies in pre-operative NSCLC. Ongoing clinical trials investigating ICIs as neoadjuvant and adjuvant therapies are also summarized.
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Project description:Surgery or concurrent chemoradiation are standard of care treatments for patients with localized and locally advanced non-small cell lung cancer (NSCLC). While resection and chemoradiation are potentially curative therapies for early-stage disease, relapse rates remain high. Adjuvant or neoadjuvant chemotherapy improves cure rates 5-15% compared with surgery alone for patients with resectable disease. Immune checkpoint inhibitors (ICI) have heralded a new era for the treatment of advanced NSCLC with one-third of patients experiencing long-term survival. There is increasing interest in examining the role of ICI therapy in patients with early-stage NSCLC. Consolidation durvalumab after chemoradiation has become a part of standard of care for patients with inoperable, locally advanced disease. More recently, there is emerging evidence that neoadjuvant treatment with ICIs results in substantial rates of major pathologic response and pathologic complete response, and high rates of R0 resection with no significant delay in time to surgery. Furthermore, preliminary data show that adjuvant treatment with ICIs after adjuvant chemotherapy improves disease-free survival and may play a critical role in reducing disease recurrence in patients with resectable disease. In this review, we discuss recently reported and ongoing studies that are designed to define the role of immunotherapy in patients with non-metastatic NSCLC.
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