PMID- 20573926 OWN - NLM STAT- MEDLINE DCOM- 20100629 LR - 20241219 IS - 1533-4406 (Electronic) IS - 0028-4793 (Linking) VI - 362 IP - 25 DP - 2010 Jun 24 TI - Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. PG - 2380-8 LID - 10.1056/NEJMoa0909530 [doi] AB - BACKGROUND: Non-small-cell lung cancer with sensitive mutations of the epidermal growth factor receptor (EGFR) is highly responsive to EGFR tyrosine kinase inhibitors such as gefitinib, but little is known about how its efficacy and safety profile compares with that of standard chemotherapy. METHODS: We randomly assigned 230 patients with metastatic, non-small-cell lung cancer and EGFR mutations who had not previously received chemotherapy to receive gefitinib or carboplatin-paclitaxel. The primary end point was progression-free survival; secondary end points included overall survival, response rate, and toxic effects. RESULTS: In the planned interim analysis of data for the first 200 patients, progression-free survival was significantly longer in the gefitinib group than in the standard-chemotherapy group (hazard ratio for death or disease progression with gefitinib, 0.36; P<0.001), resulting in early termination of the study. The gefitinib group had a significantly longer median progression-free survival (10.8 months, vs. 5.4 months in the chemotherapy group; hazard ratio, 0.30; 95% confidence interval, 0.22 to 0.41; P<0.001), as well as a higher response rate (73.7% vs. 30.7%, P<0.001). The median overall survival was 30.5 months in the gefitinib group and 23.6 months in the chemotherapy group (P=0.31). The most common adverse events in the gefitinib group were rash (71.1%) and elevated aminotransferase levels (55.3%), and in the chemotherapy group, neutropenia (77.0%), anemia (64.6%), appetite loss (56.6%), and sensory neuropathy (54.9%). One patient receiving gefitinib died from interstitial lung disease. CONCLUSIONS: 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. (UMIN-CTR number, C000000376.) CI - 2010 Massachusetts Medical Society FAU - Maemondo, Makoto AU - Maemondo M AD - Miyagi Cancer Center, Miyagi, Japan. FAU - Inoue, Akira AU - Inoue A FAU - Kobayashi, Kunihiko AU - Kobayashi K FAU - Sugawara, Shunichi AU - Sugawara S FAU - Oizumi, Satoshi AU - Oizumi S FAU - Isobe, Hiroshi AU - Isobe H FAU - Gemma, Akihiko AU - Gemma A FAU - Harada, Masao AU - Harada M FAU - Yoshizawa, Hirohisa AU - Yoshizawa H FAU - Kinoshita, Ichiro AU - Kinoshita I FAU - Fujita, Yuka AU - Fujita Y FAU - Okinaga, Shoji AU - Okinaga S FAU - Hirano, Haruto AU - Hirano H FAU - Yoshimori, Kozo AU - Yoshimori K FAU - Harada, Toshiyuki AU - Harada T FAU - Ogura, Takashi AU - Ogura T FAU - Ando, Masahiro AU - Ando M FAU - Miyazawa, Hitoshi AU - Miyazawa H FAU - Tanaka, Tomoaki AU - Tanaka T FAU - Saijo, Yasuo AU - Saijo Y FAU - Hagiwara, Koichi AU - Hagiwara K FAU - Morita, Satoshi AU - Morita S FAU - Nukiwa, Toshihiro AU - Nukiwa T CN - North-East Japan Study Group LA - eng PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - N Engl J Med JT - The New England journal of medicine JID - 0255562 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Quinazolines) RN - BG3F62OND5 (Carboplatin) RN - EC 2.7.10.1 (ErbB Receptors) RN - P88XT4IS4D (Paclitaxel) RN - S65743JHBS (Gefitinib) SB - IM CIN - N Engl J Med. 2010 Oct 14;363(16):1578-9; author reply 1579-80. doi: 10.1056/NEJMc1008506. PMID: 20942679 CIN - N Engl J Med. 2010 Oct 14;363(16):1579; author reply 1579-80. doi: 10.1056/NEJMc1008506. PMID: 20949670 MH - Aged MH - Antineoplastic Agents/therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Carboplatin/administration & dosage MH - Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics/secondary MH - ErbB Receptors/antagonists & inhibitors/genetics MH - Female MH - Gefitinib MH - *Genes, erbB-1 MH - Humans MH - Lung Neoplasms/*drug therapy/*genetics/pathology MH - Male MH - Middle Aged MH - Mutation MH - Paclitaxel/administration & dosage MH - Protein Kinase Inhibitors/*therapeutic use MH - Quinazolines/*therapeutic use MH - Survival Analysis FIR - Kobayashi, K IR - Kobayashi K FIR - Inoue, A IR - Inoue A FIR - Yamazaki, K IR - Yamazaki K FIR - Oizumi, S IR - Oizumi S FIR - Isobe, H IR - Isobe H FIR - Saijo, Y IR - Saijo Y FIR - Hagiwara, K IR - Hagiwara K FIR - Gemma, A IR - Gemma A FIR - Nukiwa, T IR - Nukiwa T FIR - Kudoh, S IR - Kudoh S FIR - Kanazawa, M IR - Kanazawa M FIR - Nagao, K IR - Nagao K FIR - Nakai, Y IR - Nakai Y FIR - Shibuya, M IR - Shibuya M FIR - Akie, K IR - Akie K FIR - Chonabayashi, N IR - Chonabayashi N FIR - Hasegawa, Y IR - Hasegawa Y FIR - Hayashibara, K IR - Hayashibara K FIR - Hino, M IR - Hino M FIR - Hino, T IR - Hino T FIR - Ikebuchi, K IR - Ikebuchi K FIR - Ishii, Y IR - Ishii Y FIR - Kaneko, N IR - Kaneko N FIR - Kimura, Y IR - Kimura Y FIR - Koba, H IR - Koba H FIR - Kojima, T IR - Kojima T FIR - Kosaihira, S IR - Kosaihira S FIR - Koyama, N IR - Koyama N FIR - Miki, H IR - Miki H FIR - Minegishi, Y IR - Minegishi Y FIR - Morikawa, N IR - Morikawa N FIR - Moriyama, G IR - Moriyama G FIR - Murayama, Y IR - Murayama Y FIR - Nagashima, M IR - Nagashima M FIR - Niizuma, K IR - Niizuma K FIR - Nitanai, H IR - Nitanai H FIR - Ogura, S IR - Ogura S FIR - Okamoto, Y IR - Okamoto Y FIR - Osaki, Y IR - Osaki Y FIR - Sakai, H IR - Sakai H FIR - Sugita, H IR - Sugita H FIR - Suzuki, T IR - Suzuki T FIR - Tanaka, J IR - Tanaka J FIR - Tokunaga, H IR - Tokunaga H FIR - Tsukamoto, T IR - Tsukamoto T FIR - Uematsu, K IR - Uematsu K FIR - Usui, K IR - Usui K FIR - Yasuda, K IR - Yasuda K EDAT- 2010/06/25 06:00 MHDA- 2010/06/30 06:00 CRDT- 2010/06/25 06:00 PHST- 2010/06/25 06:00 [entrez] PHST- 2010/06/25 06:00 [pubmed] PHST- 2010/06/30 06:00 [medline] AID - 362/25/2380 [pii] AID - 10.1056/NEJMoa0909530 [doi] PST - ppublish SO - N Engl J Med. 2010 Jun 24;362(25):2380-8. doi: 10.1056/NEJMoa0909530.