Gefitinib Versus Pemetrexed as Second-Line Treatment in Patients With Nonsmall Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy (KCSG-LU08-01): An Open-Label, Phase 3 Trial

• Published in: Cancer Vol. 118; no. 24; pp. 6234 - 6242
• Main Authors: SUN, Jong-Mu, KI HYEONG LEE, IN GYU HWANG, LEE, Keehyun, SOOK JUNG JO, JAE WON LEE, JIN SEOK AHN, PARK, Keunchil, AHN, Myung-Ju, KIM, Sang-We, DAE HO LEE, YOUNG JOO MIN, HWAN JUNG YUN, HOON KYO KIM, HONG SUK SONG, YEUL HONG KIM, KIM, Bong-Seog
• Format: Journal Article
• Language: English
• Published: Hoboken, NJ Wiley-Blackwell 15-12-2012
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adult; Aged; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Disease Progression; Female; Follow-Up Studies; Glutamates - therapeutic use; Guanine - analogs & derivatives; Guanine - therapeutic use; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm Staging; Organoplatinum Compounds - therapeutic use; Pemetrexed; Pneumology; Prognosis; Prospective Studies; Quinazolines - therapeutic use; Salvage Therapy; Survival Rate; Tumors; Tumors of the respiratory system and mediastinum; Antineoplastic agent; Phase III trial; Quinazoline derivatives; Lung cancer; non-small cell lung carcinoma; Antifolate; Cancerology; Platinum; Bronchus disease; Second line treatment; Gefitinib; Protein-tyrosine kinase; Human; Lung disease; Enzyme; Tyrosine kinase inhibitor; Respiratory disease; Transferases; nonsmall cell lung cancer; Enzyme inhibitor; Malignant tumor; Pemetrexed; Chemotherapy; Treatment; Comparative study; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.27630

Gefitinib was compared with pemetrexed as second-line therapy in a clinically selected population previously treated with platinum-based chemotherapy.
A phase 3 trial of gefitinib (250 mg/day) versus pemetrexed (500 mg/m(2) on day 1, every 3 weeks) was conducted in patients who had never smoked and who had advanced pulmonary adenocarcinoma treated with 1 previous platinum-based regimen. The primary endpoint was progression-free survival (PFS).
A total of 135 patients were analyzed. The gefitinib group had significantly longer PFS compared with the pemetrexed group, with a median PFS time of 9.0 versus 3.0 months (P = .0006). The objective response rates were 58.8% and 22.4% for gefitinib and pemetrexed, respectively (P < .001). However, there was no statistically significant difference in overall survival between the 2 groups (22.2 vs 18.9 months; P = .37). The difference of PFS was increased in a subgroup analysis of 33 patients with activating epidermal growth factor receptor mutation (15.7 vs 2.9 months; hazard ratio, 0.3; 95% confidence interval, 0.13-0.72; P = .005), with numerical superiority of gefitinib in the 38 patients testing negative for epidermal growth factor receptor mutation (5.9 vs 2.7 months; P = .099). Both regimens were well tolerated. There were no significantly different changes in quality of life between the 2 groups, except that symptom scores for dyspnea and diarrhea favored the gefitinib and pemetrexed arms, respectively.
Gefitinib showed superior efficacy to pemetrexed as second-line therapy in Korean never-smokers with pulmonary adenocarcinoma.