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Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art.

ABSTRACT: Lung cancer mortality has decreased over the past decade and can be partly attributed to advances in targeted therapy and immunotherapy. Immune checkpoint inhibitors (ICIs) have rapidly evolved from investigational drugs to standard of care for the treatment of metastatic non-small cell lung cancer (NSCLC). In particular, antibodies that block inhibitory immune checkpoints, such as programmed cell death protein 1 (PD-1) and programmed cell death 1 ligand 1 (PD-L1), have revolutionized the treatment of advanced NSCLC, when administered alone or in combination with chemotherapy. Immunotherapy is associated with higher response rates, improved overall survival (OS), and increased tolerability compared with conventional cytotoxic chemotherapy. These benefits may increase the utility of immunotherapy and its combinational use with chemotherapy in the neoadjuvant treatment of patients with NSCLC. Early findings from various ongoing clinical trials suggest that neoadjuvant ICIs alone or combined with chemotherapy may significantly reduce systemic recurrence and improve long-term OS or cure rates in resectable NSCLC. Here we further summarize the safety and efficacy of various neoadjuvant treatment regimens including immunotherapy from ongoing clinical trials and elaborate the role of neoadjuvant immunotherapy in patients with resectable NSCLC. In addition, we discuss several unresolved challenges, including the evaluations to assess neoadjuvant immunotherapy response, the role of adjuvant treatment after neoadjuvant immunotherapy, the efficacy of treatment for oncogenic-addicted tumors, and predictive biomarkers. We also provide our perspective on ways to overcome current obstacles and establish neoadjuvant immunotherapy as a standard of care.

SUBMITTER: Kang J

PROVIDER: S-EPMC8045926 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Lung cancer is the leading cause of cancer mortality and non-small cell lung cancer (NSCLC) accounts for more than 85% of all lung cancers. Platinum-based doublet chemotherapy is the standard first-line treatment for metastatic NSCLC when genomic testing reveals no targetable alteration such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) or ROS1 translocation/re-arrangements. But, chemotherapy produces response rates ranging only between 15-30%. For patients whose disease progresses on first-line chemotherapy, second-line therapy historically consists of taxane-based salvage chemotherapy with a response rate of less than 25%. Recently, immunotherapy with checkpoint inhibitor agents have demonstrated responses in advanced NSCLC, with some patients exhibiting durable responses after discontinuing therapy. In 2015, two immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), nivolumab and pembrolizumab were approved for second-line therapy of NSCLC. In 2016, another checkpoint inhibitor targeting program death-ligand 1 (PD-L1), atezolizumab was approved for the same indication. Moreover, pembrolizumab also received approval in 2016 for first-line NSCLC treatment in patients with high PD-L1 expressing tumors. Immunotherapy for NSCLC has therefore, recently evolved into a true treatment modality with the acceptance of PD-1 and PD-L1 inhibitors as the new standard of care for second-line treatment. However, it is still at the discretion of the treating physician whether to use PD-1 or PD-L1 inhibitor as data to compare these two pathways is lacking. Focus is now also on exploring their role in the adjuvant and consolidation settings for NSCLC as well as on exploring novel combinations combining these agents with chemotherapy or radiation. Research is also needed in the development of predictive and prognostic biomarkers for these agents. While vaccine therapy trials in NSCLC have so far failed to show significant clinical benefit, the demonstration of enhanced immune response in these trials suggest the vaccine therapy needs additional evaluation in combination with other therapeutic modalities especially checkpoint inhibition.

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Neoadjuvant immunotherapy for non-small cell lung cancer: State of the art.

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