ISEL試験で「プラセボ比較で有意差をだせず」、INTEREST試験で「タキソテールとの非劣性がやっと確認でき」、IPASS試験でアジアの進行非小細胞肺がん患者でEGFR遺伝子変異陽性患者を対象に、「カルボプラチン＋パクリタキセル併用化学療法に非劣性を示した」イレッサgefitinibが、カルボプラチン＋パクリタキセル併用化学療法が１年という生存期間に対して、生存期間２年という結果をだして、試験を早期に中断した。
N Engl J Med. 2010 Jun 24;362(25):2380-8.
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
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.) 2010 Massachusetts Medical Society
気づき）
・転移を伴う EGFR 変異陽性非小細胞肺癌患者が対象。
・イレッサ投与群約100人に対して間質性肺炎３名で、うち１名死亡。
・EGFR 変異に基づいて選択した進行非小細胞肺癌患者に対し，第一選択薬としてゲフィチニブを投与した場合，標準的化学療法を行った場合と比較して無増悪生存期間が改善し，毒性も許容範囲内であった→許容範囲か？
これから）
医療安全委員会、県病薬の管理指導調査へフィードバック、声門閉鎖事例の倫理委員会、月曜日なのでブックファーストに
コメント