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
TLDR
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.Abstract:
Summary Background 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. We aimed to assess the safety and efficacy of erlotinib compared with standard chemotherapy for first-line treatment of European patients with advanced EGFR-mutation positive NSCLC. Methods We undertook the open-label, randomised phase 3 EURTAC trial at 42 hospitals in France, Italy, and Spain. Eligible participants were adults (>18 years) with NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) with no history of chemotherapy for metastatic disease (neoadjuvant or adjuvant chemotherapy ending ≥6 months before study entry was allowed). We randomly allocated participants (1:1) according to a computer-generated allocation schedule to receive oral erlotinib 150 mg per day or 3 week cycles of standard intravenous chemotherapy of cisplatin 75 mg/m 2 on day 1 plus docetaxel (75 mg/m 2 on day 1) or gemcitabine (1250 mg/m 2 on days 1 and 8). Carboplatin (AUC 6 with docetaxel 75 mg/m 2 or AUC 5 with gemcitabine 1000 mg/m 2 ) was allowed in patients unable to have cisplatin. Patients were stratified by EGFR mutation type and Eastern Cooperative Oncology Group performance status (0 vs 1 vs 2). The primary endpoint was progression-free survival (PFS) in the intention-to-treat population. We assessed safety in all patients who received study drug (≥1 dose). This study is registered with ClinicalTrials.gov, number NCT00446225. Findings Between Feb 15, 2007, and Jan 4, 2011, 174 patients with EGFR mutations were enrolled. One patient received treatment before randomisation and was thus withdrawn from the study; of the remaining patients, 86 were randomly assigned to receive erlotinib and 87 to receive standard chemotherapy. The preplanned interim analysis showed that the study met its primary endpoint; enrolment was halted, and full evaluation of the results was recommended. At data cutoff (Jan 26, 2011), median PFS was 9·7 months (95% CI 8·4-12·3) in the erlotinib group, compared with 5·2 months (4·5–5·8) in the standard chemotherapy group (hazard ratio 0·37, 95% CI 0·25–0·54; p vs none of 82 patients in the chemotherapy group), neutropenia (none vs 18 [22%]), anaemia (one [1%] vs three [4%]), and increased amino-transferase concentrations (two [2%] vs 0). Five (6%) patients on erlotinib had treatment-related severe adverse events compared with 16 patients (20%) on chemotherapy. One patient in the erlotinib group and two in the standard chemotherapy group died from treatment-related causes. Interpretation Our findings strengthen the rationale for routine baseline tissue-based assessment of EGFR mutations in patients with NSCLC and for treatment of mutation-positive patients with EGFR tyrosine-kinase inhibitors. Funding Spanish Lung Cancer Group, Roche Farma, Hoffmann-La Roche, and Red Tematica de Investigacion Cooperativa en Cancer.read more
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Journal ArticleDOI
Osimertinib in Untreated EGFR-Mutated Advanced Non–Small-Cell Lung Cancer
Jean-Charles Soria,Yuichiro Ohe,Johan Vansteenkiste,Thanyanan Reungwetwattana,Busyamas Chewaskulyong,Ki Hyeong Lee,Arunee Dechaphunkul,Fumio Imamura,Naoyuki Nogami,Takayasu Kurata,Isamu Okamoto,Caicun Zhou,Byoung Chul Cho,Ying Cheng,Eun Kyung Cho,Pei Jye Voon,David Planchard,Wu Chou Su,Jhanelle E. Gray,Siow-Ming Lee,Rachel Hodge,Marcelo Marotti,Yuri Rukazenkov,Suresh S. Ramalingam +23 more
TL;DR: Osimertinib showed efficacy superior to that of standard EGFR‐TKIs in the first‐line treatment of EGFR mutation–positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events.
Journal ArticleDOI
Crizotinib versus Chemotherapy in Advanced ALK-Positive Lung Cancer
Alice T. Shaw,Dong Wan Kim,Kazuhiko Nakagawa,Takashi Seto,Lucio Crinò,Myung-Ju Ahn,Tommaso De Pas,Benjamin Besse,Benjamin Solomon,Fiona H Blackhall,Yi-Long Wu,Michael Thomas,Kenneth J. O'Byrne,Denis Moro-Sibilot,D. Ross Camidge,Tony Mok,Vera Hirsh,Gregory J. Riely,Shrividya Iyer,V. Tassell,Anna Polli,Keith D. Wilner,Pasi A. Jänne +22 more
TL;DR: Crizotinib is superior to standard chemotherapy in patients with previously treated, advanced non-small-cell lung cancer with ALK rearrangement and greater improvement in global quality of life with crizotinIB than with chemotherapy.
Journal ArticleDOI
First-line crizotinib versus chemotherapy in ALK-positive lung cancer
Benjamin Solomon,Tony Mok,Dong Wan Kim,Yi-Long Wu,Kazuhiko Nakagawa,Tarek Mekhail,Enriqueta Felip,Federico Cappuzzo,Jolanda Paolini,Tiziana Usari,Shrividya Iyer,Arlene Reisman,Keith D. Wilner,Jennifer M. Tursi,Fiona H Blackhall +14 more
TL;DR: Crizotinib was superior to standard first-line pemetrexed-plus-platinum chemotherapy in patients with previously untreated advanced ALK-positive NSCLC and was associated with greater reduction in lung cancer symptoms and greater improvement in quality of life.
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.
Journal ArticleDOI
The biology and management of non-small cell lung cancer
TL;DR: Continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.
References
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New Guidelines to Evaluate the Response to Treatment in Solid Tumors
Patrick Therasse,Susan G. Arbuck,Elizabeth Eisenhauer,Jantien Wanders,Richard Kaplan,Larry Rubinstein,Jaap Verweij,Martine Van Glabbeke,Allan T. van Oosterom,Michaele C. Christian,S. Gwyther +10 more
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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.
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EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.
J. Guillermo Paez,Pasi A. Jänne,Pasi A. Jänne,Jeffrey C. Lee,Sean Tracy,Heidi Greulich,Heidi Greulich,Stacey Gabriel,Paula Herman,Frederic J. Kaye,Neal I. Lindeman,Titus J. Boggon,Katsuhiko Naoki,Hidefumini Sasaki,Yoshitaka Fujii,Michael J. Eck,William R. Sellers,William R. Sellers,William R. Sellers,Bruce E. Johnson,Bruce E. Johnson,Matthew Meyerson,Matthew Meyerson +22 more
TL;DR: Results suggest that EGFR mutations may predict sensitivity to gefitinib, and treatment with the EGFR kinase inhibitor gefitsinib causes tumor regression in some patients with NSCLC, more frequently in Japan.
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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.
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