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      First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

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          Abstract

          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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          A Confidence Interval for the Median Survival Time

          Ron Brookmeyer, John Crowley (1982)
          Article 0 comments Cited 136 times – based on 0 reviews     Review now
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            PD-L1 expression in small cell neuroendocrine carcinomas.

            Anne M Schultheis, Andreas Scheel, Luka Ozretić … (2015)
            Small cell lung cancer and extrapulmonary small cell carcinomas are the most aggressive type of neuroendocrine carcinomas. Clinical treatment relies on conventional chemotherapy and radiotherapy; relapses are frequent. The PD-1/PD-L1/PD-L2 pathway is a major target of anti-tumour immunotherapy. Aberrant PD-L1 or PD-L2 expression may cause local immune-suppression. Here we investigated expression of PD-1 and its ligands by immunohistochemistry and RNA-seq in small cell carcinomas. PD-L1 and PD-1 protein expression were analysed in 94 clinical cases of small cell carcinomas (61 pulmonary, 33 extrapulmonary) by immunohistochemistry using two different monoclonal antibodies (5H1, E1L3N). RNA expression was profiled by RNA-seq in 43 clinical cases. None of the small cell carcinomas showed PD-L1 protein expression in tumour cells. PD-L1 and PD-1 expression was noticed in the stroma: Using immunohistochemistry, 18.5% of cases (17/92) showed PD-L1 expression in tumour-infiltrating macrophages and 48% showed PD-1 positive lymphocytes (45/94). RNA-seq showed moderate PD-L1 gene expression in 37.2% (16/43). PD-L1 was correlated with macrophage and T-cell markers. The second PD-1 ligand PD-L2 was expressed in 27.9% (12/43) and showed similar correlations. Thus, the PD-1/PD-L1 pathway seems activated in a fraction of small cell carcinomas. The carcinoma cells were negative in all cases, PD-L1 was expressed in tumour-infiltrating macrophages and was correlated with tumour-infiltrating lymphocytes. Patients with stromal PD-L1/PD-L2 expression may respond to anti-PD-1 treatment. Thus, evaluation of the composition of the tumour microenvironment should be included in clinical trials. Besides conventional immunohistochemistry, RNA-seq seems suitable for detection of PD-L1/PD-L2 expression and might prove to be more sensitive.
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              Phase II Study of Maintenance Pembrolizumab in Patients with Extensive-Stage Small Cell Lung Cancer (SCLC)

              Shirish Gadgeel, Nathan A. Pennell, Mary Jo Fidler … (2018)
              The aim of this study was to assess the efficacy of maintenance pembrolizumab in patients with extensive-stage SCLC after treatment with platinum and etoposide.
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                Author and article information

                Journal
                Title: New England Journal of Medicine
                Abbreviated Title: N Engl J Med
                Publisher: New England Journal of Medicine (NEJM/MMS)
                ISSN (Print): 0028-4793
                ISSN (Electronic): 1533-4406
                Publication date Created: September 25 2018
                Publication date (Electronic): September 25 2018
                Affiliations
                [1 ]From Vanderbilt University Medical Center (L. Horn) and Sarah Cannon Research Institute–Tennessee Oncology (M.L.J.), Nashville; Mayo Clinic, Rochester, MN (A.S.M.); Mazowieckie Centrum Leczenia Chorób Płuc i Gruźlicy, Otwock (A. Szczęsna), and Centrum Onkologii–Instytut im. Marii Skłodowskiej-Curie w Warszawie, Warsaw (M.K.) — both in Poland; Thomayerova Nemocnice, Pneumologická Klinika 1.LF UK, Prague, Czech Republic (L. Havel); the Department of Respiratory and Critical Care Medicine (M.J.H.) and the...
                Article
                DOI: 10.1056/NEJMoa1809064
                PubMed ID: 30280641
                SO-VID: aef4af81-34de-48bf-8d46-862c25076cef
                Copyright © © 2018
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                http://www.nejmgroup.org/legal/terms-of-use.htm

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