Sonam Puri1, Andreas Saltos2, Bradford Perez2, Xiuning Le3, Jhanelle E Gray4. 1. Division of Medical Oncology, The University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA. 2. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. 3. Department of Thoracic and Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. 4. Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA. jhanelle.gray@moffitt.org.
Abstract
PURPOSE OF REVIEW: Treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) has recently been revolutionized by the incorporation of immunotherapy to standard platinum-based concurrent chemoradiation. This review examines the current standard practices and ongoing studies on the management of locally advanced, unresectable NSCLC. RECENT FINDINGS: Concurrent chemoradiation is the cornerstone of treatment of unresectable, locally advanced NSCLC. However, chemoradiation can be associated with high therapy-related toxicities, and risk of disease relapse remains significantly elevated despite treatment with curative intent. Durvalumab, a PD-L1 inhibitor, was recently approved as consolidation therapy following concurrent chemoradiation; this agent represents a major advancement in treatment of unresectable stage III NSCLC. Several clinical trials are currently underway to evaluate the benefit of different immunotherapy sequencing and other biomarker-driven strategies in this disease setting. Multiple trials are presently ongoing to assess novel immunotherapy and targeted therapy strategies to improve outcomes and decrease treatment-associated toxicities in patients with locally advanced NSCLC.
PURPOSE OF REVIEW: Treatment of locally advanced, unresectable non-small cell lung cancer (NSCLC) has recently been revolutionized by the incorporation of immunotherapy to standard platinum-based concurrent chemoradiation. This review examines the current standard practices and ongoing studies on the management of locally advanced, unresectable NSCLC. RECENT FINDINGS: Concurrent chemoradiation is the cornerstone of treatment of unresectable, locally advanced NSCLC. However, chemoradiation can be associated with high therapy-related toxicities, and risk of disease relapse remains significantly elevated despite treatment with curative intent. Durvalumab, a PD-L1 inhibitor, was recently approved as consolidation therapy following concurrent chemoradiation; this agent represents a major advancement in treatment of unresectable stage III NSCLC. Several clinical trials are currently underway to evaluate the benefit of different immunotherapy sequencing and other biomarker-driven strategies in this disease setting. Multiple trials are presently ongoing to assess novel immunotherapy and targeted therapy strategies to improve outcomes and decrease treatment-associated toxicities in patients with locally advanced NSCLC.
Authors: Steven E Schild; William L McGinnis; David Graham; Shauna Hillman; Tom R Fitch; Donald Northfelt; Yolanda I Garces; Homayoon Shahidi; Loren K Tschetter; Paul L Schaefer; Alex Adjei; James Jett Journal: Int J Radiat Oncol Biol Phys Date: 2006-05-26 Impact factor: 7.038
Authors: Jeffrey D Bradley; Kyounghwa Bae; Mary V Graham; Roger Byhardt; Ramaswamy Govindan; Jack Fowler; James A Purdy; Jeff M Michalski; Elizabeth Gore; Hak Choy Journal: J Clin Oncol Date: 2010-04-05 Impact factor: 44.544
Authors: Charles Butts; Mark A Socinski; Paul L Mitchell; Nick Thatcher; Libor Havel; Maciej Krzakowski; Sergiusz Nawrocki; Tudor-Eliade Ciuleanu; Lionel Bosquée; José Manuel Trigo; Alexander Spira; Lise Tremblay; Jan Nyman; Rodryg Ramlau; Gun Wickart-Johansson; Peter Ellis; Oleg Gladkov; José Rodrigues Pereira; Wilfried Ernst Erich Eberhardt; Christoph Helwig; Andreas Schröder; Frances A Shepherd Journal: Lancet Oncol Date: 2013-12-09 Impact factor: 41.316
Authors: W Sause; P Kolesar; I V Taylor S; D Johnson; R Livingston; R Komaki; B Emami; W Curran; R Byhardt; A R Dar; A Turrisi Journal: Chest Date: 2000-02 Impact factor: 9.410
Authors: Rafael Santana-Davila; Kiran Devisetty; Aniko Szabo; Rodney Sparapani; Carlos Arce-Lara; Elizabeth M Gore; Amy Moran; Christina D Williams; Michael J Kelley; Jeffrey Whittle Journal: J Clin Oncol Date: 2014-11-24 Impact factor: 44.544
Authors: Walter J Curran; Rebecca Paulus; Corey J Langer; Ritsuko Komaki; Jin S Lee; Stephen Hauser; Benjamin Movsas; Todd Wasserman; Seth A Rosenthal; Elizabeth Gore; Mitchell Machtay; William Sause; James D Cox Journal: J Natl Cancer Inst Date: 2011-09-08 Impact factor: 13.506
Authors: Scott J Antonia; Augusto Villegas; Davey Daniel; David Vicente; Shuji Murakami; Rina Hui; Takayasu Kurata; Alberto Chiappori; Ki H Lee; Maike de Wit; Byoung C Cho; Maryam Bourhaba; Xavier Quantin; Takaaki Tokito; Tarek Mekhail; David Planchard; Young-Chul Kim; Christos S Karapetis; Sandrine Hiret; Gyula Ostoros; Kaoru Kubota; Jhanelle E Gray; Luis Paz-Ares; Javier de Castro Carpeño; Corinne Faivre-Finn; Martin Reck; Johan Vansteenkiste; David R Spigel; Catherine Wadsworth; Giovanni Melillo; Maria Taboada; Phillip A Dennis; Mustafa Özgüroğlu Journal: N Engl J Med Date: 2018-09-25 Impact factor: 91.245
Authors: Julie K Jang; Scott M Atay; Li Ding; Elizabeth A David; Sean C Wightman; Anthony W Kim; Jason C Ye Journal: Am J Clin Oncol Date: 2022-04-01 Impact factor: 2.339