PURPOSE: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. MATERIALS AND METHODS: In this open-label phase II trial, patients with resected stage IA to IIIA (7th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%. RESULTS: Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months. CONCLUSION: Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.
PURPOSE: Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non-small-cell lung cancer (NSCLC), we tested adjuvant erlotinib in patients with EGFR-mutant early-stage NSCLC. MATERIALS AND METHODS: In this open-label phase II trial, patients with resected stage IA to IIIA (7th edition of the American Joint Committee on Cancer staging system) EGFR-mutant NSCLC were treated with erlotinib 150 mg per day for 2 years after standard adjuvant chemotherapy with or without radiotherapy. The study was designed for 100 patients and powered to demonstrate a primary end point of 2-year disease-free survival (DFS) greater than 85%, improving on historic data of 76%. RESULTS: Patients (N = 100) were enrolled at seven sites from January 2008 to May 2012; 13% had stage IA disease, 32% had stage IB disease, 11% had stage IIA disease, 16% had stage IIB disease, and 28% had stage IIIA disease. Toxicities were typical of erlotinib; there were no grade 4 or 5 adverse events. Forty percent of patients required erlotinib dose reduction to 100 mg per day and 16% to 50 mg per day. The intended 2-year course was achieved in 69% of patients. The median follow-up was 5.2 years, and 2-year DFS was 88% (96% stage I, 78% stage II, 91% stage III). Median DFS and overall survival have not been reached; 5-year DFS was 56% (95% CI, 45% to 66%), 5-year overall survival was 86% (95% CI, 77% to 92%). Disease recurred in 40 patients, with only four recurrences during erlotinib treatment. The median time to recurrence was 25 months after stopping erlotinib. Of patients with recurrence who underwent rebiopsy (n = 24; 60%), only one had T790M mutation detected. The majority of patients with recurrence were retreated with erlotinib (n = 26; 65%) for a median duration of 13 months. CONCLUSION: Patients with EGFR-mutant NSCLC treated with adjuvant erlotinib had an improved 2-year DFS compared with historic genotype-matched controls. Recurrences were rare for patients receiving adjuvant erlotinib, and patients rechallenged with erlotinib after recurrence experienced durable benefit.
Authors: Arlene Chan; Suzette Delaloge; Frankie A Holmes; Beverly Moy; Hiroji Iwata; Vernon J Harvey; Nicholas J Robert; Tajana Silovski; Erhan Gokmen; Gunter von Minckwitz; Bent Ejlertsen; Stephen K L Chia; Janine Mansi; Carlos H Barrios; Michael Gnant; Marc Buyse; Ira Gore; John Smith; Graydon Harker; Norikazu Masuda; Katarina Petrakova; Angel Guerrero Zotano; Nicholas Iannotti; Gladys Rodriguez; Pierfrancesco Tassone; Alvin Wong; Richard Bryce; Yining Ye; Bin Yao; Miguel Martin Journal: Lancet Oncol Date: 2016-02-10 Impact factor: 41.316
Authors: Joan H Schiller; David Harrington; Chandra P Belani; Corey Langer; Alan Sandler; James Krook; Junming Zhu; David H Johnson Journal: N Engl J Med Date: 2002-01-10 Impact factor: 91.245
Authors: Heikki Joensuu; Mikael Eriksson; Kirsten Sundby Hall; Jörg T Hartmann; Daniel Pink; Jochen Schütte; Giuliano Ramadori; Peter Hohenberger; Justus Duyster; Salah-Eddin Al-Batran; Marcus Schlemmer; Sebastian Bauer; Eva Wardelmann; Maarit Sarlomo-Rikala; Bengt Nilsson; Harri Sihto; Odd R Monge; Petri Bono; Raija Kallio; Aki Vehtari; Mika Leinonen; Thor Alvegård; Peter Reichardt Journal: JAMA Date: 2012-03-28 Impact factor: 56.272
Authors: Martin Reck; Delvys Rodríguez-Abreu; Andrew G Robinson; Rina Hui; Tibor Csőszi; Andrea Fülöp; Maya Gottfried; Nir Peled; Ali Tafreshi; Sinead Cuffe; Mary O'Brien; Suman Rao; Katsuyuki Hotta; Melanie A Leiby; Gregory M Lubiniecki; Yue Shentu; Reshma Rangwala; Julie R Brahmer Journal: N Engl J Med Date: 2016-10-08 Impact factor: 91.245
Authors: Sandra P D'Angelo; Yelena Y Janjigian; Nicholas Ahye; Gregory J Riely; Jamie E Chaft; Camelia S Sima; Ronglai Shen; Junting Zheng; Joseph Dycoco; Mark G Kris; Maureen F Zakowski; Marc Ladanyi; Valerie Rusch; Christopher G Azzoli Journal: J Thorac Oncol Date: 2012-12 Impact factor: 15.609
Authors: Karen Kelly; Nasser K Altorki; Wilfried E E Eberhardt; Mary E R O'Brien; David R Spigel; Lucio Crinò; Chun-Ming Tsai; Joo-Hang Kim; Eun Kyung Cho; Philip C Hoffman; Sergey V Orlov; Piotr Serwatowski; Jiuzhou Wang; Margaret A Foley; Julie D Horan; Frances A Shepherd Journal: J Clin Oncol Date: 2015-08-31 Impact factor: 44.544
Authors: Pasi A Jänne; James Chih-Hsin Yang; Dong-Wan Kim; David Planchard; Yuichiro Ohe; Suresh S Ramalingam; Myung-Ju Ahn; Sang-We Kim; Wu-Chou Su; Leora Horn; Daniel Haggstrom; Enriqueta Felip; Joo-Hang Kim; Paul Frewer; Mireille Cantarini; Kathryn H Brown; Paul A Dickinson; Serban Ghiorghiu; Malcolm Ranson Journal: N Engl J Med Date: 2015-04-30 Impact factor: 91.245