JCO：难治性非小细胞肺癌厄洛替尼加舒尼替尼似不优于单药

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JCO：难治性非小细胞肺癌厄洛替尼加舒尼替尼似不优于单药
2012-05-10
基于涉及肿瘤生长，血管生成和转移的信号通路的重要性，非小细胞肺癌（NSCLC）舒尼替尼和厄洛替尼联用相比各自单用，抗肿瘤活性要更强。于是来自意大利都灵大学的Giorgio V. Scagliotti等人进行了一项3期临床试验，用于比较舒尼替尼加上厄洛替尼与安慰剂加厄洛替尼治疗难治性非小细胞肺癌患者的总生存（OS）率。

纳入患者为复发性非小细胞肺癌患者，先前已予以1到2个化疗方案（包含以铂类为基础的方案）化疗。患者被随机分为2组（1:1），1组予以舒尼替尼37.5mg/ d加厄洛替尼150mg/ d，另一组予以安慰剂加上厄洛替尼150mg/d，分层因素：先前是否使用过贝伐单抗，吸烟史和表皮生长因子受体表达情况。主要终点：总生存率。重要的次要终点包括无进展生存时间（PFS），客观应答率（ORR）和安全性。

最终此项研究纳入960例患者。中位OS舒尼替尼加厄洛替尼为9.0个月，厄洛替尼单用为8.5个月（风险比[HR]为0.922;95％CI：0.797-1.067; 分层单侧Log-rank检验P=0.1388）。中位PFS分别为3.6个月和2.0个月（HR，0.807;95％CI，0.695-0.937; 分层单侧Log-rank检验P=0.0023），ORR分别为10.6％和6.9％（分层双侧Log-rank检验P =0.0471）。治疗相关的3级以上毒性，包括皮疹/皮炎，腹泻，乏力/疲劳，舒尼替尼加厄洛替尼组更为常见。

由此可得出结论：厄洛替尼加舒尼替尼不能改善难治性非小细胞肺癌患者的总生存率，但可以改善PFS和ORR。不过联合用药会出现更多的3级以上毒性反应

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相关文献
Sunitinib Plus Erlotinib Versus Placebo Plus Erlotinib in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer: A Phase III Trial.
J Clin Oncol 2012;:

Scagliotti GV Krzakowski M Szczesna A Strausz J Makhson A Reck M Wierzbicki RF Albert I Thomas M Miziara JE Papai ZS Karaseva N Thongprasert S Dalmau Portulas E von Pawel J Zhang K Selaru P Tye L Chao RC Govindan R

Giorgio V. Scagliotti, University of Turin, Orbassano (Turin), Italy; Maciej Krzakowski, Maria Sklodowska-Curie Memorial Institute of Oncology, Warsaw; Aleksandra Szczesna, Regional Lung Diseases Hospital, Otwock, Poland; Janos Strausz, Koranyi National Institute for Pulmonology, Budapest; Istvan Albert, Matrai Gyogyintezet, Matrahaza; Zsolt S. Papai, Fejer Megyei Szent Gyorgy Korhaz, Szekesfehervar, Hungary; Anatoly Makhson, Moscow City Clinical Hospital of Oncology #62, Moscow; Nina Karaseva, City Clinical Oncology Dispensary, St. Petersburg, Russian Federation; Martin Reck, Hospital Grosshansdorf, Grosshansdorf; Michael Thomas, Thoracic Clinic, University of Heidelberg, Heidelberg; Joachim von Pawel, Asklepios-Fachklinik München-Gauting, Gauting, Germany; Rafal F. Wierzbicki, R.S. McLaughlin Durham Regional Cancer Centre, Lakeridge Health, Oshawa, Ontario, Canada; Jose Elias Abrao Miziara, Hospital de Cancer de Barretos, Barretos, Brazil; Sumitra Thongprasert, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Elsa Dalmau Portulas, Corporació Parc Taulí, Hospital de Sabadell, Barcelona, Spain; Ke Zhang, Paulina Selaru, Lesley Tye, and Richard C. Chao, Pfizer Oncology, La Jolla, CA; and Ramaswamy Govindan, Washington University School of Medicine, St. Louis, MO.

Abstract
PURPOSESunitinib plus erlotinib may enhance antitumor activity compared with either agent alone in non-small-cell lung cancer (NSCLC), based on the importance of the signaling pathways involved in tumor growth, angiogenesis, and metastasis. This phase III trial investigated overall survival (OS) for sunitinib plus erlotinib versus placebo plus erlotinib in patients with refractory NSCLC. PATIENTS AND METHODSPatients previously treated with one to two chemotherapy regimens (including one platinum-based regimen) for recurrent NSCLC, and for whom erlotinib was indicated, were randomly assigned (1:1) to sunitinib 37.5 mg/d plus erlotinib 150 mg/d or to placebo plus erlotinib 150 mg/d, stratified by prior bevacizumab use, smoking history, and epidermal growth factor receptor expression. The primary end point was OS. Key secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.ResultsIn all, 960 patients were randomly assigned, and baseline characteristics were balanced. Median OS was 9.0 months for sunitinib plus erlotinib versus 8.5 months for erlotinib alone (hazard ratio [HR], 0.922; 95% CI, 0.797 to 1.067; one-sided stratified log-rank P = .1388). Median PFS was 3.6 months versus 2.0 months (HR, 0.807; 95% CI, 0.695 to 0.937; one-sided stratified log-rank P = .0023), and ORR was 10.6% versus 6.9% (two-sided stratified log-rank P = .0471), respectively. Treatment-related toxicities of grade 3 or higher, including rash/dermatitis, diarrhea, and asthenia/fatigue were more frequent in the sunitinib plus erlotinib arm. CONCLUSIONIn patients with refractory NSCLC, sunitinib plus erlotinib did not improve OS compared with erlotinib alone, but the combination was associated with a statistically significantly longer PFS and greater ORR. The incidence of grade 3 or higher toxicities was greater with combination therapy.