Emiliano Calvo博士，START马德里工作组主任、西班牙圣保罗CEU大学教授，在第六届国际肾癌高峰论坛（CORE）上做了题为“Controversies in Targeted Therapy for mRCC”的演讲，并就mRCC二线靶向治疗于会后接受了《肿瘤瞭望》的专访。

《肿瘤瞭望》：依维莫司在老年转移性肾细胞癌（mRCC）患者中的疗效和耐受性如何？

Calvo教授: RECORD-1试验的前瞻性亚组分析针对依维莫司和安慰剂在老年患者中的耐受性和疗效进行了研究。RECORD-1试验在大众人群中的结果在该研究的老年患者中也得以重现。依维莫司良好的耐受性使其成为非常适合老年患者的靶向治疗药物。

Oncology Frontier: Is everolimus more effective and tolerable in elderly patients with mRCC? What are the main factors that we should consider when selecting targeted therapies in elderly patients?

Dr.Calvo: There is a prospective subgroup analysis from the RECORD-1 study that analyzes the tolerance and activity of everolimus versus placebo in this population of elderly patients. The results of RECORD-1 in the general population are reproduced in the elderly population of this study. The good tolerance profile of everolimus makes it a very appropriate drug for patients who are more fragile as one would expect in the elderly population.

《肿瘤瞭望》：如何为VEGF-TKI治疗进展的肾细胞癌患者选择合适的二线治疗方案?

Calvo教授:目前有两种药物被推荐应用于VEGF-TKI治疗进展的转移性肾细胞癌患者，分别为阿昔替尼和依维莫司。这两种药物的抗肿瘤活性直接比较下来基本相似，那么如何选择药物关键在于药物的耐受性和毒副反应，以我个人经验来说，在TKI治疗后的二线治疗方案中依维莫司的耐受性更好，因为序贯两种TKIs药物可以观察到药物毒性的累积。

Oncology Frontier: What is the optimal therapy for patients with metastatic renal cell carcinoma who progress on an initial VEGFR-TKI? Which factors should be considered when selecting a second-line therapy for patients with VEGFR-TKIrefractory RCC?

Dr.Calvo:There are two drugs that are accepted as recommended for second-line therapy after progression on VEGFR-TKIs - axitinib and everolimus. Their anti-tumor activity in direct comparisons is so similar that the most important factor in this context is tolerability and toxicity profile. In my opinion， everolimus is better tolerated in second-line therapy after TKI because of the cumulative toxicity we see when we administer two TKIs sequentially.

《肿瘤瞭望》：mRCC的二线靶向治疗中，您认为哪种序贯方案更优？

Calvo教授:个人认为，VEGF-TKI序贯mTOR抑制剂方案优于TKI序贯TKI方案，但其实目前还是很难明确推荐一种方案，因为尚没有头对头比较TKI序贯TKI与序贯mTOR的研究。基于现有的所有与二线治疗疗效相关的数据来说，疗效似乎都差不多，但很明确的一点就是由于剂量限制毒性， TKI序贯TKI时需要降低剂量的患者比例显著高于TKI序贯mTOR抑制剂（依维莫司）方案。

Oncology Frontier: What sequence should we choose in mRCC? Is a VEGFR-TKI/mTOR inhibitor sequence better than a TKI/TKI sequence?

Dr.Calvo: Yes. But it is difficult to state in a definitive way because we don’t have a study specifically designed to compare sequential TKIs to TKI and mTOR in a head-to-head comparison. Based on the available data regarding activity of both sequences in second-line therapy， they appear to be equally effective in anti-tumor activity but it is very clear that the percentage of patients who require dose reduction when receiving a second TKI following the initial TKI， is much higher than the percentage of patients requiring dose reduction because of toxicity where the mTOR inhibitor (everolimus) follows the VEGFR-TKI in second-line.

《肿瘤瞭望》：对于减瘤性肾切除患者，应如何选择全身治疗？

Calvo教授:除了原发瘤以外，患者其实还有转移的病灶。有研究表明，减瘤性肾切除术可以改善转移性肾细胞癌患者的生存。在行减瘤性肾切除术后，这些患者往往还需要接受系统的全身治疗。当我们需要在TKI治疗和细胞因子（例如干扰素）治疗中做出选择时，有随机临床试验显示舒尼替尼或其他TKI优于干扰素，尤其是在减瘤术后，更加优于细胞因子治疗。

Oncology Frontier:Debulking nephrectomy has been shown to improve survival in metastatic renal cell carcinoma. Should patients receive VEGFR-TKI as targeted therapy or interferon as a watch-and-wait approach followed by debulking nephrectomy?

Dr.Calvo:In addition to the primary tumor， there are metastatic lesions in the patient. After proceeding with a debulking nephrectomy， systemic therapy is usually required for these patients. Where we have to choose between a TKI or a cytokine (like interferon)， it is clearlydemonstrated in randomized trials that sunitinib or other TKI is better than interferon in this setting and clearly more indicated after the debulking nephrectomy than cytokines.