Prolonging Survival: The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Small Cell Lung Cancer

The oncologist

article

Barbara Melosky¹  Natasha Leighl²  Quincy Chu³  Parneet K. Cheema⁴  Anthony Brade⁵  Deanna McLeod⁶  Geoffrey Liu²  Paul Wheatley Price⁷  Kevin Jao⁸  Devin D. Schellenberg⁹  Rosalyn Juergens^1,10 

[1] Vancouver Centre, University of British Columbia;Princess Margaret Cancer Centre, University of Toronto;Cross Cancer Institute, University of Alberta;William Osler Health System, University of Toronto;Trillium Health Partners, University of Toronto;Kaleidoscope Strategic Inc.;The Ottawa Hospital, University of Ottawa;Hôpital Sacré-Cœur, Université de Montréal;Surrey Centre, University of British Columbia;Juravinski Cancer Centre, McMaster University

关键词: Small cell lung cancer;    Immune checkpoint inhibitors;    First-line;    Atezolizumab;    Durvalumab;   

DOI  :  10.1634/theoncologist.2020-0193

学科分类：地质学

来源: AlphaMed Press Incorporated

【 摘 要 】

Background Small cell lung cancer (SCLC) represents approximately 15% of lung cancers, and approximately 70% are diagnosed as extensive-stage SCLC (ES-SCLC). Although ES-SCLC is highly responsive to chemotherapy, patients typically progress rapidly, and there is an urgent need for new therapies. Immune checkpoint inhibitors (ICIs) have recently been investigated in SCLC, and this review provides guidance on the use of these agents in ES-SCLC based on phase III evidence. Methods Published and presented literature on phase III data addressing use of ICIs in ES-SCLC was identified using the key search terms “small cell lung cancer” AND “checkpoint inhibitors” (OR respective aliases). Directed searches of eligible studies were periodically performed to ensure capture of the most recent data. Results Six phase III trials were identified, with four assessing the benefits of ICIs plus chemotherapy first-line, one evaluating ICIs as first-line therapy maintenance, and one assessing ICI monotherapy after progression on platinum-based chemotherapy. The addition of ipilimumab or tremelimumab to first-line treatment or as first-line maintenance did not improve survival. Two out of three studies combining PD-1/PD-L1 inhibitors with first-line platinum-based chemotherapy demonstrated significant long-lasting survival benefits and improved quality of life with no unexpected safety concerns. PD-1/PD-L1 inhibitors as first-line maintenance or in later lines of therapy did not improve survival. Biomarker research is ongoing as well as research into the role of ICIs in combination with radiation therapy in limited-stage SCLC. Conclusion The addition of atezolizumab or durvalumab to first-line platinum-based chemotherapy for ES-SCLC prolongs survival and improves quality of life. Implications for Practice Platinum-based chemotherapy has been standard of care for extensive-stage small cell lung cancer (ES-SCLC) for more than a decade. Six recent phase III trials investigating immune checkpoint inhibitors (ICIs) have clarified the role of these agents in this setting. Although ICIs were assessed first-line, as first-line maintenance, and in later lines of therapy, the additions of atezolizumab or durvalumab to first-line platinum-based chemotherapy were the only interventions that significantly improved overall survival and increased quality of life. These combinations should therefore be considered standard therapy for first-line ES-SCLC. Biomarker research and investigations into the role of ICIs for limited-stage disease are ongoing.

【 授权许可】

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