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      Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer

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          Abstract

          The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.

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          Most cited references109

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          Cancer statistics, 2022

          Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths in the United States and compiles the most recent data on population-based cancer occurrence and outcomes. Incidence data (through 2018) were collected by the Surveillance, Epidemiology, and End Results program; the National Program of Cancer Registries; and the North American Association of Central Cancer Registries. Mortality data (through 2019) were collected by the National Center for Health Statistics. In 2022, 1,918,030 new cancer cases and 609,360 cancer deaths are projected to occur in the United States, including approximately 350 deaths per day from lung cancer, the leading cause of cancer death. Incidence during 2014 through 2018 continued a slow increase for female breast cancer (by 0.5% annually) and remained stable for prostate cancer, despite a 4% to 6% annual increase for advanced disease since 2011. Consequently, the proportion of prostate cancer diagnosed at a distant stage increased from 3.9% to 8.2% over the past decade. In contrast, lung cancer incidence continued to decline steeply for advanced disease while rates for localized-stage increased suddenly by 4.5% annually, contributing to gains both in the proportion of localized-stage diagnoses (from 17% in 2004 to 28% in 2018) and 3-year relative survival (from 21% to 31%). Mortality patterns reflect incidence trends, with declines accelerating for lung cancer, slowing for breast cancer, and stabilizing for prostate cancer. In summary, progress has stagnated for breast and prostate cancers but strengthened for lung cancer, coinciding with changes in medical practice related to cancer screening and/or treatment. More targeted cancer control interventions and investment in improved early detection and treatment would facilitate reductions in cancer mortality.
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            Pembrolizumab plus Chemotherapy in Metastatic Non–Small-Cell Lung Cancer

            First-line therapy for advanced non-small-cell lung cancer (NSCLC) that lacks targetable mutations is platinum-based chemotherapy. Among patients with a tumor proportion score for programmed death ligand 1 (PD-L1) of 50% or greater, pembrolizumab has replaced cytotoxic chemotherapy as the first-line treatment of choice. The addition of pembrolizumab to chemotherapy resulted in significantly higher rates of response and longer progression-free survival than chemotherapy alone in a phase 2 trial.
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              Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial

              First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater.
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                Author and article information

                Contributors
                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                17 May 2023
                2023
                : 13
                : 1145128
                Affiliations
                [1] 1 Department of Thoracic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine , Hangzhou, China
                [2] 2 Department of Thoracic Surgery, Longyou County People’s Hospital , Longyou, China
                Author notes

                Edited by: Min Li, Central South University, China

                Reviewed by: Qingquan Luo, Shanghai Jiao Tong University, China; Yang Gao, Central South University, China

                *Correspondence: Zhengfu He, hezhengfu@ 123456zju.edu.cn
                Article
                10.3389/fonc.2023.1145128
                10229830
                37265800
                64518a76-a875-44bf-8d39-1e600101130a
                Copyright © 2023 Wang, Huang, Feng, Xu, Luo, Zhu, Zeng and He

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 15 January 2023
                : 03 May 2023
                Page count
                Figures: 1, Tables: 0, Equations: 0, References: 109, Pages: 10, Words: 4739
                Funding
                Funded by: Science and Technology Department of Zhejiang Province , doi 10.13039/501100008990;
                Funded by: National Natural Science Foundation of China , doi 10.13039/501100001809;
                This work was supported by the Major Research Project of the Science and Technology Department of Zhejiang Province (grant number 2021C03124) and the National Natural Science Foundation of China (grant number 82103305).
                Categories
                Oncology
                Review
                Custom metadata
                Thoracic Oncology

                Oncology & Radiotherapy
                non-small cell lung cancer,neoadjuvant immunotherapy,chemo-immunotherapy,efficacy prediction,biomarkers

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