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Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer.

ABSTRACT: The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/- radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and effective therapeutic strategy for the treatment of advanced NSCLC. Therefore, it is possible that ICIs for early-stage NSCLC may follow the pattern established in metastatic disease. Currently, there are several ongoing trials to determine the efficacy in the neoadjuvant setting for patients with local or regional disease. To date, only nivolumab in combination with chemotherapy has been approved by the U.S. FDA in the preoperative setting, but data continue to evolve rapidly, and treatment guidelines need to be determined. In this article, we review the current preclinical and clinical evidence on neoadjuvant ICIs alone and combination in the treatment of early-stage NSCLC.

SUBMITTER: Riano I

PROVIDER: S-EPMC9963056 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer.

Riano Ivy I Abuali Inas I Sharma Aditya A Durant Jewelia J Dragnev Konstantin H KH

Pharmaceuticals (Basel, Switzerland) 20230203 2

The neoadjuvant use of immune checkpoint inhibitors (ICI) in resectable non-small cell lung cancer (NSCLC) is being increasingly adopted, but questions about the most appropriate applications remain. Although patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy or targeted therapies +/- radiotherapy, they still have a high risk of recurrence and death. In recent years, immune checkpoint inhibitors (ICI) (anti-PD-1/PD-L1 and anti-CTLA-4) have provided a new and ...[more]

PMID: 37259381

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Project description:BackgroundOur objective was to explore the safety and feasibility of immune checkpoint inhibitors (ICIs) in the neoadjuvant treatment of non-small cell lung cancer (NSCLC).MethodsEmbase, PubMed and Web of Science were systematically searched from 1st January 2018 to 1st August 2021 for studies with data on the treatment-related adverse reactions (TRAE), immune-related adverse events (irAE), perioperative information, major pathological response (MPR), pathologic complete remission (pCR) and objective response rate (ORR). The QUADAS-2 tool was used to assess the quality of the studies, then the data were transformed for meta-analysis. Review Manager 5.3 (Cochrane) was used for statistical analyses with a P value of <0.05 considered significant.ResultsThirteen studies with 358 patients were included in this meta-analysis, of which, 218 patients received ICI and chemotherapy-containing regimens and 140 patients received neoadjuvant ICIs only. The 157 (72.0%) patients who received combined neoadjuvant therapy showed a higher incidence of TRAEs, while only 37 (26.4%) patients who received neoadjuvant ICIs experienced TRAEs. Grade 3 or higher irAEs were observed in 92 (25.7%) patients, of which, 81 patients belonged to the neoadjuvant immunochemotherapy subgroup. The surgical resection rate was between 38.5-100%, with only two patients experiencing a delay in surgery. Complication rates were between 3.6-100% in the 8 studies that reported postoperative complications, with more postoperative complications [35 (18.9%)] identified in the neoadjuvant immunochemotherapy subgroup. Of which 176 patients achieved MPR, 126 received ICI and chemotherapy combined neoadjuvant therapy. Seventy-one of 95 patients who had achieved pCR had undergone ICI and chemotherapy. Compared with the neoadjuvant immunotherapy group, patients undergoing ICI and chemotherapy achieved more radiological response [118 (54.1%)] than patients undergoing ICIs [25 (17.9%)] only. The odds ratio (OR) value of the MPR/pCR/ORR rate in the neoadjuvant immunochemotherapy group was higher [OR =0.55/0.32/0.39, 95% confidence interval (CI): 0.44-0.66/0.22-0.44/0.26-0.53, P=0.0004/0.14/<0.0001] after transformation.DiscussionNeoadjuvant immunotherapy shows lower toxicity and fewer perioperative complications. ICI combined chemotherapy can achieve more pathological relief and clinical benefits in the neoadjuvant treatment of NSCLC but is associated with increased irAE and perioperative complications. However, the small sample size limits the reliability of the research.

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Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer.

Publications

Role of Neoadjuvant Immune Checkpoint Inhibitors in Resectable Non-Small Cell Lung Cancer.

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