Journal ArticleDOI
Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): A phase 2 trial
James Chih-Hsin Yang,Jin-Yuan Shih,Wu Chou Su,Te Chun Hsia,Chun-Ming Tsai,Sai-Hong Ignatius Ou,Chung Jen Yu,Gee-Chen Chang,C. L. Ho,Lecia V. Sequist,Arkadiusz Z. Dudek,Mehdi Shahidi,X.J. Cong,Robert M. Lorence,Pan-Chyr Yang,Vincent A. Miller +15 more
TLDR
Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations, and should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC.Abstract:
Summary Background Afatinib is an irreversible ErbB-family blocker with preclinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. We aimed to assess the efficacy of afatinib in patients with lung adenocarcinoma and EGFR mutations. Methods In this phase 2 study, we enrolled patients from 30 centres in Taiwan and the USA with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) with EGFR mutations, who had no more than one previous chemotherapy regimen for advanced disease, an Eastern Cooperative Oncology Group performance status of 0–2, and no previous treatment with EGFR tyrosine-kinase inhibitors. We tested two afatinib starting doses: 50 mg daily and subsequently 40 mg daily, introduced to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). This study is registered with ClinicalTrials.gov, number NCT00525148. Findings 129 patients were treated with afatinib, 99 with a starting dose of 50 mg and 30 with a starting dose of 40 mg. 79 (61%) of 129 patients had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 patients with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 patients with less common mutations. Similar proportions of patients had an objective response when analysed by starting dose (18 [60%] of 30 patients at 40 mg vs 61 [62%] of 99 patients at 50 mg). Of the two most common adverse events (diarrhoea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 [22%] of 99 patients for diarrhoea and 28 [28%] of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two [7%] of 30 patients for both diarrhoea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). We recorded one possibly drug-related death (interstitial lung disease). Interpretation Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations. The efficacy of afatinib 40 mg should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC. Funding Boehringer Ingelheim Inc.read more
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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
Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials
James Chih-Hsin Yang,Yi-Long Wu,Martin Schuler,Martin Sebastian,Sanjay Popat,Nobuyuki Yamamoto,Caicun Zhou,Cheng Ping Hu,Kenneth J. O'Byrne,Jifeng Feng,Shun Lu,Yunchao Huang,Sarayut Lucien Geater,Kye Young Lee,Chun-Ming Tsai,Vera Gorbunova,Vera Hirsh,Jaafar Bennouna,S. M. Orlov,Tony Mok,Michael Boyer,Wu Chou Su,Ki Hyeong Lee,Terufumi Kato,Dan Massey,Mehdi Shahidi,Victoria Zazulina,Lecia V. Sequist +27 more
TL;DR: In this article, the effect of Afatinib on overall survival of patients with EGFR mutation-positive lung adenocarcinoma through an analysis of data from two open-label, randomised, phase 3 trials was evaluated.
Journal ArticleDOI
Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial
Vincent A. Miller,Vincent A. Miller,Vera Hirsh,Jacques Cadranel,Yuh Min Chen,Keunchil Park,Sang We Kim,Caicun Zhou,Wu Chou Su,M. Wang,Yan Sun,Dae Seog Heo,Lucio Crinò,Eng Huat Tan,Tsu Yi Chao,Mehdi Shahidi,X.J. Cong,Robert M. Lorence,James Chih-Hsin Yang +18 more
TL;DR: The findings for progression-free survival and response to treatment suggest that afatinib could be of some benefit to patients with advanced lung adenocarcinoma who have failed at least 12 weeks of previous EGFR tyrosine-kinase inhibitor treatment.
Journal ArticleDOI
Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6.
James Chih-Hsin Yang,Lecia V. Sequist,Sarayut Lucien Geater,Chun-Ming Tsai,Tony Mok,Martin Schuler,Nobuyuki Yamamoto,Chong-Jen Yu,Sai-Hong Ignatius Ou,Caicun Zhou,Dan Massey,Victoria Zazulina,Yi-Long Wu +12 more
TL;DR: Afatinib was active in non-small-cell lung cancer tumours that harboured certain types of uncommon EGFR mutations, especially Gly719Xaa, Leu861Gln, and Ser768Ile, but less active in other mutations types.
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Journal ArticleDOI
Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib
Thomas J. Lynch,Daphne W. Bell,Raffaella Sordella,Sarada Gurubhagavatula,Ross A. Okimoto,Brian W. Brannigan,Patricia L. Harris,Sara M. Haserlat,Jeffrey G. Supko,Frank G. Haluska,David N. Louis,David C. Christiani,Jeff Settleman,Daniel A. Haber +13 more
TL;DR: A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib, and these mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor.
Journal ArticleDOI
Gefitinib or Carboplatin–Paclitaxel in Pulmonary Adenocarcinoma
Tony Mok,Yi-Long Wu,Sumitra Thongprasert,Chih-Hsin Yang,Da Tong Chu,Nagahiro Saijo,Patrapim Sunpaweravong,Baohui Han,Benjamin Margono,Benjamin Margono,Yukito Ichinose,Yutaka Nishiwaki,Yuichiro Ohe,Jin Ji Yang,Busyamas Chewaskulyong,Haiyi Jiang,Emma Duffield,Claire Watkins,Alison Armour,Masahiro Fukuoka +19 more
TL;DR: Gefit inib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia and the presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib.
Journal ArticleDOI
Gefitinib or Chemotherapy for Non–Small-Cell Lung Cancer with Mutated EGFR
Makoto Maemondo,Akira Inoue,Kunihiko Kobayashi,Shunichi Sugawara,Satoshi Oizumi,Hiroshi Isobe,Akihiko Gemma,Masao Harada,Hirohisa Yoshizawa,Ichiro Kinoshita,Yuka Fujita,Shoji Okinaga,Haruto Hirano,Kozo Yoshimori,Toshiyuki Harada,Takashi Ogura,Masahiro Ando,Hitoshi Miyazawa,Tomoaki Tanaka,Yasuo Saijo,Koichi Hagiwara,Satoshi Morita,Toshihiro Nukiwa +22 more
TL;DR: First-line gefitinib for patients with advanced non-small-cell lung cancer who were selected on the basis of EGFR mutations improved progression-free survival, with acceptable toxicity, as compared with standard chemotherapy.
Journal ArticleDOI
Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial.
Rafael Rosell,Enric Carcereny,Radj Gervais,A. Vergnenegre,Bartomeu Massuti,Enriqueta Felip,Ramon Palmero,Ramon Garcia-Gomez,Cinta Pallares,Jose Miguel Sanchez,Rut Porta,Manuel Cobo,Pilar Garrido,Flavia Longo,Teresa Moran,A. Insa,Filippo de Marinis,Romain Corre,Isabel Bover,Alfonso Illiano,Eric Dansin,Javier de Castro,Michele Milella,Noemi Reguart,Giuseppe Altavilla,Ulpiano Jimenez,Mariano Provencio,Miguel Angel Moreno,J. Terrasa,Jose Muñoz-Langa,Javier Valdivia,Dolores Isla,Manuel Domine,Olivier Molinier,Julien Mazieres,Nathalie Baize,Rosario García-Campelo,Gilles Robinet,Delvys Rodriguez-Abreu,Guillermo Lopez-Vivanco,Vittorio Gebbia,Lioba Ferrera-Delgado,Pierre Bombaron,R. Bernabé,Alessandra Bearz,Angel Artal,Enrico Cortesi,Christian Rolfo,Maria Sanchez-Ronco,Ana Drozdowskyj,Cristina Queralt,Itziar de Aguirre,Jose Luis Ramirez,Jose Javier Sanchez,Miguel Angel Molina,Miquel Taron,Luis Paz-Ares +56 more
TL;DR: Erlotinib has been shown to improve progression-free survival compared with chemotherapy when given as first-line treatment for Asian patients with non-small-cell lung cancer (NSCLC) with activating EGFR mutations as discussed by the authors.
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