BACKGROUND: Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. METHODS: In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) orcarboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. RESULTS: The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. CONCLUSIONS:Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.) 2009 Massachusetts Medical Society
RCT Entities:
BACKGROUND: Previous, uncontrolled studies have suggested that first-line treatment with gefitinib would be efficacious in selected patients with non-small-cell lung cancer. METHODS: In this phase 3, open-label study, we randomly assigned previously untreated patients in East Asia who had advanced pulmonary adenocarcinoma and who were nonsmokers or former light smokers to receive gefitinib (250 mg per day) (609 patients) or carboplatin (at a dose calculated to produce an area under the curve of 5 or 6 mg per milliliter per minute) plus paclitaxel (200 mg per square meter of body-surface area) (608 patients). The primary end point was progression-free survival. RESULTS: The 12-month rates of progression-free survival were 24.9% with gefitinib and 6.7% with carboplatin-paclitaxel. The study met its primary objective of showing the noninferiority of gefitinib and also showed its superiority, as compared with carboplatin-paclitaxel, with respect to progression-free survival in the intention-to-treat population (hazard ratio for progression or death, 0.74; 95% confidence interval [CI], 0.65 to 0.85; P<0.001). In the subgroup of 261 patients who were positive for the epidermal growth factor receptor gene (EGFR) mutation, progression-free survival was significantly longer among those who received gefitinib than among those who received carboplatin-paclitaxel (hazard ratio for progression or death, 0.48; 95% CI, 0.36 to 0.64; P<0.001), whereas in the subgroup of 176 patients who were negative for the mutation, progression-free survival was significantly longer among those who received carboplatin-paclitaxel (hazard ratio for progression or death with gefitinib, 2.85; 95% CI, 2.05 to 3.98; P<0.001). The most common adverse events were rash or acne (in 66.2% of patients) and diarrhea (46.6%) in the gefitinib group and neurotoxic effects (69.9%), neutropenia (67.1%), and alopecia (58.4%) in the carboplatin-paclitaxel group. CONCLUSIONS:Gefitinib is superior to carboplatin-paclitaxel as an initial treatment for pulmonary adenocarcinoma among nonsmokers or former light smokers in East Asia. The presence in the tumor of a mutation of the EGFR gene is a strong predictor of a better outcome with gefitinib. (ClinicalTrials.gov number, NCT00322452.) 2009 Massachusetts Medical Society
Authors: Alan P Venook; Maria E Arcila; Al B Benson; Donald A Berry; David Ross Camidge; Robert W Carlson; Toni K Choueiri; Valerie Guild; Gregory P Kalemkerian; Razelle Kurzrock; Christine M Lovly; Amy E McKee; Robert J Morgan; Anthony J Olszanski; Mary W Redman; Vered Stearns; Joan McClure; Marian L Birkeland Journal: J Natl Compr Canc Netw Date: 2014-11 Impact factor: 11.908
Authors: Youngwook Kim; Peter S Hammerman; Jaegil Kim; Ji-ae Yoon; Yoomi Lee; Jong-Mu Sun; Matthew D Wilkerson; Chandra Sekhar Pedamallu; Kristian Cibulskis; Yeong Kyung Yoo; Michael S Lawrence; Petar Stojanov; Scott L Carter; Aaron McKenna; Chip Stewart; Andrey Y Sivachenko; In-Jae Oh; Hong Kwan Kim; Yong Soo Choi; Kwhanmien Kim; Young Mog Shim; Kyu-Sik Kim; Sang-Yun Song; Kook-Joo Na; Yoon-La Choi; D Neil Hayes; Jhingook Kim; Sukki Cho; Young-Chul Kim; Jin Seok Ahn; Myung-Ju Ahn; Gad Getz; Matthew Meyerson; Keunchil Park Journal: J Clin Oncol Date: 2013-12-09 Impact factor: 44.544
Authors: Martin L Sos; Felix Dietlein; Martin Peifer; Jakob Schöttle; Hyatt Balke-Want; Christian Müller; Mirjam Koker; André Richters; Stefanie Heynck; Florian Malchers; Johannes M Heuckmann; Danila Seidel; Patrick A Eyers; Roland T Ullrich; Andrey P Antonchick; Viktor V Vintonyak; Peter M Schneider; Takashi Ninomiya; Herbert Waldmann; Reinhard Büttner; Daniel Rauh; Lukas C Heukamp; Roman K Thomas Journal: Proc Natl Acad Sci U S A Date: 2012-10-03 Impact factor: 11.205