Vallet Sonia, Pahernik Sascha, Höfner Thomas, Tosev Georgi, Hadaschik Boris, Duensing Stefan, Sedlaczek Oliver, Hohenfellner Markus, Jäger Dirk, Grüllich Carsten
Department of Medical Oncology, National Center for Tumor Diseases Heidelberg, Heidelberg University Hospital, Heidelberg, Germany.
Department of Urology, Heidelberg University Hospital, Heidelberg, Germany.
Clin Genitourin Cancer. 2015 Jun;13(3):e145-52. doi: 10.1016/j.clgc.2014.12.012. Epub 2014 Dec 30.
INTRODUCTION/BACKGROUND: Currently, 7 agents are approved for the first- and second-line therapy for metastatic renal cell carcinoma. In contrast, data supporting their use beyond second line are limited. Here we summarize our experience in patients treated with more than 4 lines of therapy.
We retrospectively assessed the outcome of 24 patients treated at our institution with at least 4 lines of therapy. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier estimates.
Median OS from the initiation of first-line therapy for the whole cohort is 64.7 months. Up to 96% of the patients received a tyrosine kinase inhibitor (TKI) and mammalian target of rapamycin (mTOR) inhibitor (mTOR-I) within the first 3 lines of treatment. In the fourth or following lines, patients were treated with TKI, mTOR-I, bevacizumab/interferon, or experimental drugs. Seven patients continued treatment with a sixth-line agent; one has been treated up to the ninth line. Sixteen percent of the patients receiving fourth-line therapy and 13% receiving fifth-line therapy experienced a partial remission, which was independent from response to previous therapies. Median OS from fourth and fifth line was 30.8 and 26.2 months, respectively. Median PFS for fourth-line therapy was 5.8 months. No significant difference in PFS was observed for patients with disease that responded or did not respond to first-line therapy.
Despite the limitations of a retrospective analysis, our study suggests that selected patients benefit from multiple lines of treatment, independent of response to first-line therapy. However, the optimal sequence of treatment with regard to later lines remains to be determined.
引言/背景：目前，有7种药物被批准用于转移性肾细胞癌的一线和二线治疗。相比之下，支持它们在二线以上使用的数据有限。在此，我们总结了接受超过4线治疗的患者的经验。
我们回顾性评估了在我们机构接受至少4线治疗的24例患者的结局。采用Kaplan-Meier估计法计算无进展生存期（PFS）和总生存期（OS）。
整个队列从一线治疗开始的中位OS为64.7个月。高达96%的患者在前三线治疗中接受了酪氨酸激酶抑制剂（TKI）和雷帕霉素哺乳动物靶点（mTOR）抑制剂（mTOR-I）。在第四线或后续治疗中，患者接受TKI、mTOR-I、贝伐单抗/干扰素或实验性药物治疗。7例患者继续接受第六线药物治疗；1例患者已接受至第九线治疗。接受第四线治疗的患者中有16%、接受第五线治疗的患者中有13%出现部分缓解，这与对先前治疗的反应无关。第四线和第五线治疗的中位OS分别为30.8个月和26.2个月。第四线治疗的中位PFS为5.8个月。对一线治疗有反应或无反应的患者在PFS方面未观察到显著差异。
尽管回顾性分析存在局限性，但我们的研究表明，部分患者可从多线治疗中获益，与对一线治疗的反应无关。然而，后续治疗的最佳顺序仍有待确定。
