Department of Medical Oncology, Ospedale Civile di Livorno, Livorno, Italy.
Lancet Oncol. 2010 Jun;11(6):521-9. doi: 10.1016/S1470-2045(10)70112-1. Epub 2010 May 20.
First-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) is usually limited to four to six cycles. Maintenance therapy can delay progression and prolong survival. The oral epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitor erlotinib has proven efficacy and tolerability in second-line NSCLC. We designed the phase 3, placebo-controlled Sequential Tarceva in Unresectable NSCLC (SATURN; BO18192) study to assess use of erlotinib as maintenance therapy in patients with non-progressive disease following first-line platinum-doublet chemotherapy.
Between December, 2005, and May, 2008, 1949 patients were included in the run-in phase (four cycles of platinum-based chemotherapy). At the end of the run-in phase, 889 patients who did not have progressive disease were entered into the main study, and were randomly allocated using a 1:1 adaptive randomisation method through a third-party interactive voice response system to receive erlotinib (150 mg/day; n=438) or placebo (n=451) until progression or unacceptable toxicity. Patients were stratified by EGFR immunohistochemistry status, stage, Eastern Cooperative Oncology Group performance status, chemotherapy regimen, smoking history, and region. Co-primary endpoints were progression-free survival (PFS) in all analysable patients irrespective of EGFR status, and PFS in patients whose tumours had EGFR protein overexpression, as determined by immunohistochemistry. This study is registered with www.ClinicalTrials.gov, number NCT00556712.
884 patients were analysable for PFS; 437 in the erlotinib group and 447 in the placebo group. After a median follow-up of 11.4 months for the erlotinib group and 11.5 months for the placebo group, median PFS was significantly longer with erlotinib than with placebo: 12.3 weeks for patients in the erlotinib group versus 11.1 weeks for those in the placebo group (HR 0.71, 95% CI 0.62-0.82; p<0.0001). PFS was also significantly longer in patients with EGFR-positive immunohistochemistry who were treated with erlotinib (n=307) compared with EGFR-positive patients given placebo (n=311; median PFS 12.3 weeks in the erlotinib group vs 11.1 weeks in the placebo group; HR 0.69, 0.58-0.82; p<0.0001). The most common grade 3 or higher adverse events were rash (37 [9%] of 443 patients in the erlotinib group vs none of 445 in the placebo group) and diarrhoea (seven [2%] of 443 patients vs none of 445). Serious adverse events were reported in 47 patients (11%) on erlotinib compared with 34 patients (8%) on placebo. The most common serious adverse event was pneumonia (seven cases [2%] with erlotinib and four [<1%] with placebo).
Maintenance therapy with erlotinib for patients with NSCLC is well tolerated and significantly prolongs PFS compared with placebo. First-line maintenance with erlotinib could be considered in patients who do not progress after four cycles of chemotherapy.
F Hoffmann-La Roche Ltd.
晚期非小细胞肺癌（NSCLC）的一线化疗通常限于四到六个周期。维持治疗可以延缓进展并延长生存期。口服表皮生长因子受体（EGFR）酪氨酸激酶抑制剂厄洛替尼已被证明在二线 NSCLC 中具有疗效和耐受性。我们设计了 III 期、安慰剂对照的不可切除 NSCLC 中厄洛替尼序贯治疗（SATURN；BO18192）研究，以评估在一线铂类双重化疗后无疾病进展的患者中使用厄洛替尼作为维持治疗。
2005 年 12 月至 2008 年 5 月，共有 1949 名患者纳入了运行阶段（铂类化疗四个周期）。在运行阶段结束时，889 名无疾病进展的患者进入了主要研究，并通过第三方交互式语音应答系统以 1:1 的适应性随机方法随机分配接受厄洛替尼（150mg/天；n=438）或安慰剂（n=451），直至进展或无法耐受毒性。患者按 EGFR 免疫组化状态、分期、东部合作肿瘤学组表现状态、化疗方案、吸烟史和地区进行分层。主要终点是所有可分析患者的无进展生存期（PFS），无论 EGFR 状态如何，以及肿瘤 EGFR 蛋白过表达的患者的 PFS，通过免疫组化确定。这项研究在 www.ClinicalTrials.gov 上注册，编号为 NCT00556712。
884 名患者可进行 PFS 分析；厄洛替尼组 437 例，安慰剂组 447 例。厄洛替尼组中位随访时间为 11.4 个月，安慰剂组为 11.5 个月，与安慰剂组相比，厄洛替尼组的中位 PFS 显著延长：厄洛替尼组为 12.3 周，安慰剂组为 11.1 周（HR 0.71，95%CI 0.62-0.82；p<0.0001）。接受厄洛替尼治疗的 EGFR 阳性免疫组化患者的 PFS 也明显长于接受安慰剂的 EGFR 阳性患者（n=307；厄洛替尼组中位 PFS 为 12.3 周，安慰剂组为 11.1 周；HR 0.69，0.58-0.82；p<0.0001）。最常见的 3 级或更高级别的不良事件是皮疹（厄洛替尼组 443 例中有 37 例[9%]，安慰剂组 445 例中无 1 例）和腹泻（厄洛替尼组 443 例中有 7 例[2%]，安慰剂组 445 例中无 1 例）。厄洛替尼组有 47 名（11%）患者发生严重不良事件，安慰剂组有 34 名（8%）患者发生严重不良事件。最常见的严重不良事件是肺炎（厄洛替尼组 7 例[2%]，安慰剂组 4 例[<1%]）。
与安慰剂相比，厄洛替尼作为 NSCLC 患者的维持治疗耐受性良好，可显著延长 PFS。对于化疗后不进展的患者，可考虑一线维持厄洛替尼治疗。
F. Hoffmann-La Roche Ltd.
