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      Role of Immunotherapy in Stage IV Large Cell Neuroendocrine Carcinoma of the Lung

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          Abstract

          Background:

          Despite approvals of immune checkpoint inhibitors in both small cell and non-small cell lung cancers, the role of immunotherapy in large cell neuroendocrine carcinoma (LCNEC) in lung is undefined.

          Methods:

          Using the National Cancer Database (NCDB), Stage IV lung LCNEC cases diagnosed from 2014 to 2016 were analyzed. Information regarding cancer treatment was limited to first course of therapy, including surgery for primary lesion, radiation, chemotherapy, and immunotherapy. Survival analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analysis.

          Results:

          Among 661 eligible cases, 37 patients were treated with immunotherapy. No significant association between use of immunotherapy and clinical demographics was observed except for use of chemotherapy (p=0.0008). Chemotherapy was administered in 34 (92%) and 406 (65%) in immunotherapy and non-immunotherapy groups, respectively. Use of immunotherapy was associated with improved overall survival (Log-rank p=0.0018). Landmark analysis in the immunotherapy group showed 12 and 18-month survivals of 34.0% and 29.1%, respectively, whereas those in the non-immunotherapy group were 24.1% and 15.0%, respectively. Multivariate analysis demonstrated that female sex (HR=0.79, p=0.0063), liver metastases (HR=0.75, p=.0392), surgery (HR= 0.50, p<0.0001) use of chemotherapy (HR= 0.44, p<0.0001), and use of immunotherapy (HR=0.64, p=0.0164) had statistical significance. Propensity score matching in overall survival analysis showed a nonsignificant trend (p=0.0733) in favor of immunotherapy treatment.

          Conclusion:

          This retrospective study using NCDB suggests that use of immunotherapy may improve survival of LCNEC patients.

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          Most cited references21

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          The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.

          The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary hamartoma," (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and
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            First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

            Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.
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              Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial

              Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum-etoposide) in treatment-naive patients with ES-SCLC.
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                Author and article information

                Journal
                Asian Pac J Cancer Prev
                Asian Pac J Cancer Prev
                APJCP
                Asian Pacific Journal of Cancer Prevention : APJCP
                West Asia Organization for Cancer Prevention (Iran )
                1513-7368
                2476-762X
                February 2021
                : 22
                : 2
                : 365-370
                Affiliations
                [1 ] Medical Oncology, Parkview Cancer Institute, 11050 Parkview Circle, Fort Wayne, IN 46845, USA.
                [2 ] Parkview Research Center, Mirro Center for Research and Innovation, 3948- A New Vision Drive, Fort Wayne, IN 46845, USA.
                Author notes
                [* ]For Correspondence: takefumi.komiya@parkview.com
                Article
                10.31557/APJCP.2021.22.2.365
                8190341
                33639649
                e41e7d9a-282f-4f7e-8927-b043c2a647b7

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 July 2020
                : 21 February 2021
                Categories
                Research Article

                immunotherapy,large cell neuroendocrine carcinoma,lung cancer

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