Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial
Jean-Charles Soria,Enriqueta Felip,Manuel Cobo,Shun Lu,Konstantinos N. Syrigos,Ki Hyeong Lee,Erdem Göker,Vassilis Georgoulias,Wei Li,Dolores Isla,Salih Zeki Guclu,Alessandro Morabito,Young Joo Min,Andrea Ardizzoni,Shirish M. Gadgeel,Bushi Wang,Vikram K. Chand,Glenwood D. Goss +17 more
TLDR
In this paper, an open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide was conducted to compare erlotinib (a reversible EGFR tyrosine kinase inhibitor) with afatinib (40 mg per day) until disease progression.Abstract:
Summary Background There is a major unmet need for effective treatments in patients with squamous cell carcinoma of the lung. LUX-Lung 8 compared afatinib (an irreversible ErbB family blocker) with erlotinib (a reversible EGFR tyrosine kinase inhibitor), as second-line treatment for patients with advanced squamous cell carcinoma of the lung. Methods We did this open-label, phase 3 randomised controlled trial at 183 cancer centres in 23 countries worldwide. We enrolled adults with stage IIIB or IV squamous cell carcinoma of the lung who had progressed after at least four cycles of platinum-based-chemotherapy. Participants were randomly assigned (1:1) to receive afatinib (40 mg per day) or erlotinib (150 mg per day) until disease progression. The randomisation was done centrally with an interactive voice or web-based response system and stratified by ethnic origin (eastern Asian vs non-eastern Asian). Clinicians and patients were not masked to treatment allocation. The primary endpoint was progression-free survival assessed by independent central review (intention-to-treat population). The key secondary endpoint was overall survival. This trial is registered with ClinicalTrials.gov, NCT01523587. Findings 795 eligible patients were randomly assigned (398 to afatinib, 397 to erlotinib). Median follow-up at the time of the primary analysis of progression-free survival was 6·7 months (IQR 3·1–10·2), at which point enrolment was not complete. Progression free-survival at the primary analysis was significantly longer with afatinib than with erlotinib (median 2·4 months [95% CI 1·9–2·9] vs 1·9 months [1·9–2·2]; hazard ratio [HR] 0·82 [95% CI 0·68–1·00], p=0·0427). At the time of the primary analysis of overall survival (median follow-up 18·4 months [IQR 13·8–22·4]), overall survival was significantly greater in the afatinib group than in the erloinib group (median 7·9 months [95% CI 7·2–8·7] vs 6·8 months [5·9–7·8]; HR 0·81 [95% CI 0·69–0·95], p=0·0077), as were progression-free survival (median 2·6 months [95% CI 2·0–2·9] vs 1·9 months [1·9–2·1]; HR 0·81 [95% CI 0·69–0·96], p=0·0103) and disease control (201 [51%] of 398 patients vs 157 [40%] of 397; p=0·0020). The proportion of patients with an objective response did not differ significantly between groups (22 [6%] vs 11 [3%]; p=0·0551). Tumour shrinkage occurred in 103 (26%) of 398 patients versus 90 (23%) of 397 patients. Adverse event profiles were similar in each group: 224 (57%) of 392 patients in the afatinib group versus 227 (57%) of 395 in the erlotinib group had grade 3 or higher adverse events. We recorded higher incidences of treatment-related grade 3 diarrhoea with afatinib (39 [10%] vs nine [2%]), of grade 3 stomatitis with afatinib (16 [4%] vs none), and of grade 3 rash or acne with erlotinib (23 [6%] vs 41 [10%]). Interpretation The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung. Funding Boehringer Ingelheim.read more
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Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †
Silvia Novello,Fabrice Barlesi,Raffaele Califano,Raffaele Califano,Tanja Cufer,Simon Ekman,M. Giaj Levra,Keith M. Kerr,Sanjay Popat,Martin Reck,Suresh Senan,G Simo,Johan Vansteenkiste,Sanne Peters +13 more
TL;DR: The ESMO Guidelines Committee concluded that current state-of-the-art oncology practices in France, Belgium, and the Netherlands are suitable for frontline use and recommend further research into these practices.
Journal ArticleDOI
Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
Gregory A. Masters,Sarah Temin,Christopher G. Azzoli,Giuseppe Giaccone,Sherman Baker,Julie R. Brahmer,Peter M. Ellis,Ajeet Gajra,Nancy Rackear,Joan H. Schiller,Thomas J. Smith,John R. Strawn,David Trent,David H. Johnson +13 more
TL;DR: This guideline update reflects changes in evidence since the previous guideline and recommends combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care.
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Systemic Therapy for Stage IV Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update
TL;DR: This guideline update reflects changes in evidence since the previous guideline and recommends combination cytotoxic chemotherapy is recommended, guided by histology, with early concurrent palliative care.
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Precision Diagnosis and Treatment for Advanced Non–Small-Cell Lung Cancer
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TL;DR: The authors of this review discuss recent progress in diagnostic and treatment approaches, including molecular characterization to determine the likelihood of a response to targeted agents and immunotherapies.
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The emerging treatment landscape of targeted therapy in non-small-cell lung cancer.
TL;DR: Recent literature is reviewed and analyzed, the targeting pathways and ongoing clinical trials in lung cancer are discussed, and optimal ways of combining targeted therapy, immunotherapy, and chemotherapy are discussed.
References
More filters
Journal ArticleDOI
Nivolumab versus docetaxel in advanced squamous-cell non-small-cell lung cancer
Julie R. Brahmer,Karen L. Reckamp,Paul Baas,Lucio Crinò,Wilfried Eberhardt,Elena Poddubskaya,Scott J. Antonia,Adam Pluzanski,Everett E. Vokes,Esther Holgado,David M. Waterhouse,Neal Ready,Justin F. Gainor,Osvaldo Arén Frontera,Libor Havel,Martin Steins,Marina Chiara Garassino,Joachim G.J.V. Aerts,Manuel Domine,Luis Paz-Ares,Martin Reck,Christine Baudelet,Christopher T. Harbison,Brian Lestini,David R. Spigel +24 more
TL;DR: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.
Journal ArticleDOI
Comprehensive genomic characterization of squamous cell lung cancers
Peter S. Hammerman,Doug Voet,Michael S. Lawrence,Douglas Voet,Rui Jing,Kristian Cibulskis,Andrey Sivachenko,Petar Stojanov,Aaron McKenna,Eric S. Lander,Eric S. Lander,Stacey Gabriel,Gad Getz,Marcin Imielinski,Elena Helman,Bryan Hernandez,Nam Pho,Matthew Meyerson,Andy Chu,Jung E. Hye-Chun,Andrew J. Mungall,Erin Pleasance,A. Gordon Robertson,Payal Sipahimalani,Dominik Stoll,Miruna Balasundaram,Inanc Birol,Yaron S.N. Butterfield,Eric Chuah,Robin J.N. Coope,Richard Corbett,Noreen Dhalla,Ranabir Guin,An He,Carrie Hirst,Martin Hirst,Robert A. Holt,Darlene Lee,Haiyan I. Li,Michael Mayo,Richard A. Moore,Karen Mungall,Ka Ming Nip,Adam B. Olshen,Jacqueline E. Schein,Jared R. Slobodan,Angela Tam,Nina Thiessen,Richard Varhol,Thomas Zeng,Yongjun Zhao,Steven J.M. Jones,Marco A. Marra,Gordon Saksena,Andrew D. Cherniack,Stephen E. Schumacher,Barbara Tabak,Scott L. Carter,Huy V. Nguyen,Robert C. Onofrio,Andrew Crenshaw,Kristin G. Ardlie,Rameen Beroukhim,Wendy Winckler,Alexei Protopopov,Alexei Protopopov,Jianhua Zhang,Jianhua Zhang,Angela Hadjipanayis,Semin Lee,Ruibin Xi,Lixing Yang,Xiaojia Ren,Hailei Zhang,Sachet A. Shukla,Peng Chieh Chen,Psalm Haseley,Eunjung Lee,Lynda Chin,Lynda Chin,Peter J. Park,Raju Kucherlapati,Nicholas D. Socci,Yupu Liang,Nikolaus Schultz,Laetitia Borsu,Alex E. Lash,Agnes Viale,Chris Sander,Marc Ladanyi,J. Todd Auman,Katherine A. Hoadley,Matthew D. Wilkerson,Yan Shi,Christina Liquori,Shaowu Meng,Ling Li,Yidi J. Turman,Michael D. Topal,Donghui Tan,Scot Waring,Elizabeth Buda,Jesse Walsh,Corbin D. Jones,Piotr A. Mieczkowski,Darshan Singh,Junyuan Wu,Anisha Gulabani,Peter Dolina,Tom Bodenheimer,Alan P. Hoyle,Janae V. Simons,Matthew G. Soloway,Joshua M. Stuart,Lisle E. Mose,Stuart R. Jefferys,Saianand Balu,Brian O'Connor,Derek Y. Chiang,Jinze Liu,Derek Y. Chiang,D. Neil Hayes,Charles M. Perou,Leslie Cope,Daniel J. Weisenberger,Ludmila Danilova,Daniel J. Weisenberger,Dennis T. Maglinte,Fei Pan,David Van Den Berg,Timothy J. Triche,James G. Herman,Stephen B. Baylin,Peter W. Laird,Michael S. Noble,Nils Gehlenborg,Daniel DiCara,Jinhua Zhang,Jinhua Zhang,Chang-Jiun Wu,Chang-Jiun Wu,Spring Yingchun Liu,Lihua Zou,Pei Lin,Juok Cho,Marc Danie Nazaire,James A. Robinson,Helga Thorvaldsdottir,Jill P. Mesirov,Rileen Sinha,Giovanni Ciriello,Ethan Cerami,Benjamin Gross,Anders Jacobsen,Jianjiong Gao,B. Arman Aksoy,Nils Weinhold,Ricardo Ramirez,Barry S. Taylor,Yevgeniy Antipin,Boris Reva,Qianxing Mo,Venkatraman E. Seshan,Paul K. Paik,Rehan Akbani,Nianxiang Zhang,Bradley M. Broom,Tod D. Casasent,Anna K. Unruh,Chris Wakefield,R. Craig Cason,Keith A. Baggerly,John N. Weinstein,David Haussler,Christopher C. Benz,Joshua M. Stuart,Jingchun Zhu,Christopher Szeto,Gary K. Scott,Christina Yau,Sam Ng,Theodore C. Goldstein,Peter Waltman,Artem Sokolov,Eric A. Collisson,Kyle Ellrott,Collisson E,Daniel R. Zerbino,Singer Ma,Brian Craft,Ying Du,Christopher R. Cabanski,Vonn Walter,James Stephen Marron,Yufeng Liu,Kai Wang,Jan F. Prins,Chad J. Creighton,Yiqun Zhang,William D. Travis,Natasha Rekhtman,Joanne Yi,Marie Christine Aubry,Richard T. Cheney,Sanja Dacic,Douglas B. Flieder,William K. Funkhouser,Peter B. Illei,Jerome Myers,Ming-Sound Tsao,Robert Penny,David Mallery,Troy Shelton,Martha Hatfield,Scott Morris,Peggy Yena,Candace Shelton,Mark Sherman,Joseph Paulauskis,Ramaswamy Govindan,Ijeoma Azodo,David G. Beer,Ron Bose,Lauren Averett Byers,David P. Carbone,Li-Wei Chang,Elizabeth Chun,Li Ding,John V. Heymach,Cristiane M. Ida,Bruce E. Johnson,Igor Jurisica,Jacob M. Kaufman,Farhad Kosari,David J. Kwiatkowski,Christopher G. Maher,William Pao,Martin Peifer,Martin Peifer,Gordon Robertson,Valerie W. Rusch,Jill M. Siegfried,Carrie Sougnez,Roman K. Thomas,Roman K. Thomas,Sandra C. Tomaszek,Charles J. Vaske,David A. Wheeler,Dennis A. Wigle,Christopher Wilks,Christopher Wilks,Jianjua John Zhang,Jianjua John Zhang,Mark A. Jensen,Robert Sfeir,Ari B. Kahn,Anna L. Chu,Prachi Kothiyal,Zhining Wang,Eric E. Snyder,Joan Pontius,Todd Pihl,Mark Backus,Jessica Walton,Julien Baboud,Dominique L. Berton,Matthew C. Nicholls,Deepak Srinivasan,Rohini Raman,Stanley Girshik,Peter A. Kigonya,Shelley Alonso,Rashmi N. Sanbhadti,Sean P. Barletta,John M. Greene,David Pot,Bizhan Bandarchi-Chamkhaleh,Jeff Boyd,JoEllen Weaver,Ijeoma A. Azodo,Sandra C. Tomaszek,Ping Yang,Malcolm V. Brock,Kristen Rogers,Marian Rutledge,Travis Brown,Beverly Lee,James Shin,Dante Trusty,Rajiv Dhir,Jill M. Siegfried,Olga Potapova,Konstantin V. Fedosenko,Maureen F. Zakowski,Elena Nemirovich-Danchenko,Mary Iacocca,Jennifer Brown,Brenda Rabeno,Christine Czerwinski,Nicholas J. Petrelli,Zhen Fan,Nicole Todaro,John Eckman,W. Kimryn Rathmell,Leigh B. Thorne,Mei Huang,Lori Boice,Ashley Hill,Erin Curley,Carl Morrison,Carmelo Gaudioso,John M. S. Bartlett,Sugy Kodeeswaran,Brent W. Zanke,Harman Sekhon,Kerstin David,Hartmut Juhl,Xuan Van Le,Bernard Kohl,Richard Thorp,Nguyen Viet Tien,Nguyen Van Bang,Howard H. Sussman,Bui Duc Phu,Richard A. Hajek,Nguyen Phi Hung,Khurram Z. Khan,Thomas Muley,Kenna R. Mills Shaw,Margi Sheth,Liming Yang,John A. Demchok,Tanja Davidsen,Kenneth H. Buetow,Greg Eley,Martin L. Ferguson,Laura A.L. Dillon,Carl F. Schaefer,Mark S. Guyer,Bradley A. Ozenberger,Jacqueline D. Palchik,Jane Peterson,Heidi J. Sofia,Elizabeth J. Thomson,Bruce E. Johnson,Ronglai Shen +345 more
TL;DR: It is shown that the tumour type is characterized by complex genomic alterations, with a mean of 360 exonic mutations, 165 genomic rearrangements, and 323 segments of copy number alteration per tumour.
Journal ArticleDOI
Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations
Lecia V. Sequist,James Chih-Hsin Yang,Nobuyuki Yamamoto,Kenneth J. O'Byrne,Vera Hirsh,Tony Mok,Sarayut Lucien Geater,Sergey Orlov,Chun-Ming Tsai,Michael Boyer,Wu Chou Su,Jaafar Bennouna,Terufumi Kato,Vera Gorbunova,Ki Hyeong Lee,Riyaz Shah,Dan Massey,Victoria Zazulina,Mehdi Shahidi,Martin Schuler +19 more
TL;DR: The LUX-Lung 3 study as mentioned in this paper investigated the efficacy of chemotherapy compared with afatinib, a selective, orally bioavailable ErbB family blocker that irreversibly blocks signaling from epidermal growth factor receptor (EGFR/ErbB1), human epIDERmal growth factors receptor 2 (HER2/ERbB2), and ErbbB4 and has wide-spectrum preclinical activity against EGFR mutations.
Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations
Lecia V. Sequist,James Chih-Hsin Yang,Nobuyuki Yamamoto,Kenneth J. O'Byrne,Vera Hirsh,Tony Mok,Sarayut Lucien Geater,Sergey Orlov,Chun-Ming Tsai,Michael Boyer,Wu Chou Su,Jaafar Bennouna,Terufumi Kato,Vera Gorbunova,Ki Hyeong Lee,Riyaz Shah,Dan Massey,Victoria Zazulina,Mehdi Shahidi,Martin Schuler +19 more
TL;DR: Afatinib is associated with prolongation of PFS when compared with standard doublet chemotherapy in patients with advanced lung adenocarcinoma and EGFR mutations.
Journal ArticleDOI
Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †
Silvia Novello,Fabrice Barlesi,Raffaele Califano,Raffaele Califano,Tanja Cufer,Simon Ekman,M. Giaj Levra,Keith M. Kerr,Sanjay Popat,Martin Reck,Suresh Senan,G Simo,Johan Vansteenkiste,Sanne Peters +13 more
TL;DR: The ESMO Guidelines Committee concluded that current state-of-the-art oncology practices in France, Belgium, and the Netherlands are suitable for frontline use and recommend further research into these practices.
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