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Review
. 2021 Jan;10(1):590-606.
doi: 10.21037/tlcr-20-573.

Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer

Affiliations
Review

Emerging biomarkers for neoadjuvant immune checkpoint inhibitors in operable non-small cell lung cancer

Monika Pradhan et al. Transl Lung Cancer Res. 2021 Jan.

Abstract

The advent of immune checkpoint inhibitors (ICIs) has dramatically changed the treatment of patients with locally advanced unresectable and metastatic non-small cell lung cancer (NSCLC). Now, ICIs are undergoing evaluation as neoadjuvant therapy in patients with early-stage, resectable NSCLC using candidate surrogate endpoints of clinical efficacy, i.e., major pathologic response (MPR, ≤10% viable tumor cells in resected tumors). The initial results from early, small-scale trials are encouraging; however, they also reveal that a substantial number of patients with operable disease may not benefit from neoadjuvant ICIs. Consequently, much investigative effort is currently directed toward identifying mechanisms of resistance to ICI therapy in resectable NSCLC. There is also an urgent need for biomarkers that could be used to guide the clinical decision-making process and maximize the clinical benefit of ICIs in patients with early-stage, resectable NSCLC. Here, we summarize the initial results from the trials of neoadjuvant ICIs in patients with early-stage and locally advanced operable NSCLC and review the findings of studies investigating emerging biomarkers associated with those trials.

Keywords: Early-stage non-small cell lung cancer (early-stage NSCLC); biomarkers; neoadjuvant immune checkpoint inhibitors.

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Conflict of interest statement

Conflicts of Interests: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-573). The series “Multimodal management of locally advanced N2 non-small cell lung cancer” was commissioned by the editorial office without any funding or sponsorship. DLG has received consulting fee from Astellas and research funding from AstraZeneca, Janssen R&D, Takeda, Ribon Therapeutics, Sanofi, Astellas and has participated in advisory boards for AstraZeneca and Sanofi. BS reports consulting fees from Bristol-Myers Squibb. TC reports speaker’s fees from Society for Immunotherapy of Cancer (SITC) and Bristol-Myers Squibb, consulting fees from MedImmune/AstraZeneca and Bristol-Myers Squibb, and advisory role fees from EMD Serono and Bristol-Myers Squibb and clinical research funding to MD Anderson Cancer Center from Boehringer Ingelheim, MedImmune/AstraZeneca, EMD Serono and Bristol-Myers Squibb. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
Biomarkers under investigation for neoadjuvant immune checkpoint inhibitors in operable NSCLC. PD-L1, programmed cell death-ligand 1; TILs, tumor infiltrating lymphocytes; TLS, tertiary lymphoid structures; TMB, tumor mutation burden; TCR, T cell receptor; ITH, intratumoral heterogeneity; SUVmax, maximum standardized uptake values; NK, natural killer cells; PD-1, programmed cell death-1; NLR, neutrophil to lymphocyte ratio; M,L, myeloid to lymphoid ratio; PLR, platelet to lymphocyte ratio; ctDNA, circulating tumor DNA; bTMB, blood-based tumor mutation burden.

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