PDF(Pubmed)
Abstract：
The immune checkpoint inhibitor/tyrosine kinase inhibitor (ICI/TKI) combination treatment is currently the first-line treatment for metastatic renal cell carcinoma (mRCC). However, its efficacy beyond the third-line setting is expected to be relatively poor, and high-grade toxicities can develop by prior exposure to multiple drugs, resulting in a relatively poor performance in patients. Determining the best treatment regimen and sequence remains difficult and requires further investigation in patients with mRCC. In this study, two cases of mRCC, who failed several lines of TKI and nivolumab but exhibited a good anticancer effect after rechallenging with axitinib, are described. Both patients had a faster time to best response and better progression-free survival (PFS) than during previous treatments. Moreover, the axitinib dose could be reduced to 2.5 mg daily when used in combination with nivolumab while continuing to exert an impressive anticancer effect. To determine the cytotoxic effect, we performed a lymphocyte activation test and found that the level of granzyme B released by cytotoxic T lymphocytes and natural killer cells was higher when axitinib was combined with nivolumab. To evaluate this result, a bioinformatics approach was used to analyze the PRISM database. In conclusion, based on the results of a lymphocyte activation test and PD-1 expression, our findings indicate that sequential therapy with axitinib rechallenge after nivolumab resistance is reasonable for the treatment of mRCC.
摘要：
免疫检查点抑制剂/酪氨酸激酶抑制剂（ICI/TKI）联合治疗是目前转移性肾细胞癌（mRCC）的一线治疗方法。然而,它在三线设置之外的功效预计会相对较差，高级毒性可以通过事先接触多种药物而发展，导致患者表现相对较差。确定最佳治疗方案和顺序仍然很困难，需要对mRCC患者进行进一步研究。在这项研究中,两例mRCC，TKI和nivolumab的几行失败，但在用阿西替尼重新挑战后表现出良好的抗癌效果，被描述。与以前的治疗相比，两名患者的最佳反应时间更快，无进展生存期（PFS）更好。此外，当与纳武单抗联合使用时,阿西替尼的剂量可以减少至每日2.5mg,同时继续发挥令人印象深刻的抗癌作用.为了确定细胞毒性作用，我们进行了淋巴细胞活化试验,发现阿西替尼联合纳武单抗时,细胞毒性T淋巴细胞和自然杀伤细胞释放的颗粒酶B水平较高.为了评估这个结果，采用生物信息学方法对PRISM数据库进行分析.总之,根据淋巴细胞活化试验和PD-1表达的结果，我们的研究结果表明,对于mRCC的治疗,nivolumab耐药后给予阿西替尼序贯治疗是合理的.
