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  • Review Article
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Novel strategies for the treatment of small-cell lung carcinoma

Abstract

Small-cell lung cancer (SCLC) is a disease with a poor prognosis and limited treatment options. Over the past 30 years, basic and clinical research have translated to little innovation in the treatment of this disease. The Study of Picoplatin Efficacy After Relapse (SPEAR) evaluated best supportive care with or without picoplatin for second-line SCLC treatment and failed to meet its primary end point of overall survival. As the largest second-line, randomized study in patients with SCLC, SPEAR provides an opportunity to critically examine the drug development model in this disease. In this Review, we discuss the current standard approach for the management of SCLC that progresses after first-line therapy, analyze the preliminary data that supported the evaluation of picoplatin in this setting, and critically evaluate the SPEAR trial design and results. Lastly, we present advances in the understanding of the molecular biology of SCLC that could potentially inform future clinical trials and hopefully lead to the successful development of molecular targeted agents for the treatment of this disease.

Key Points

  • Small-cell lung cancer (SCLC) is a disease with a poor prognosis and limited treatment options; over the past three decades, advances in systemic therapies of SCLC have been rare

  • The Study of Picoplatin Efficacy After Relapse (SPEAR) was another failed attempt at drug development for this disease and illustrates the need for better-designed treatment strategies

  • SCLCs exhibit a florid pattern of genetic abnormalities, which translate to challenges in identifying processes driving the development of the oncogenic phenotype

  • Molecular profiling of tumors is an important tool to understand the biology of SCLC and will assist in identifying potential therapeutic targets and predictive markers of treatment benefit

  • Future clinical studies should also be supported by extensive preclinical data that characterize the drug's mechanism of action and demonstrate the relevance of the drug targets to SCLC oncogenesis

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Both authors researched data and wrote the article, provided substantial contributions to the discussion of content, and reviewed and edited the manuscript before submission.

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Correspondence to Bonnie S. Glisson.

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B. S. Glisson declares that she received grant/research support (including clinical trials) from Amgen. W. N. William Jr declares no competing interests

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William, W., Glisson, B. Novel strategies for the treatment of small-cell lung carcinoma. Nat Rev Clin Oncol 8, 611–619 (2011). https://doi.org/10.1038/nrclinonc.2011.90

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