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对阿昔替尼治疗无反应的转移性肾细胞癌患者的特征。

Characteristics of patients with metastatic renal cell carcinoma who do not respond to axitinib treatment.

作者信息

Ohba Kojiro, Osawa Takahiro, Kojima Takahiro, Hara Tomohiko, Sugimoto Mikio, Eto Masatoshi, Minami Keita, Nakai Yasutomo, Ueda Kosuke, Naito Sei, Nonomura Norio, Murai Sachiyo, Nishiyama Hiroyuki, Nakanishi Hiromi, Mukae Yuta, Mitsunari Kensuke, Matsuo Tomohiro, Imamura Ryoichi, Shinohara Nobuo

机构信息

Department of Urology and Renal Transplantation, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Department of Urology, Hokkaido University Hospital, Sapporo, Japan.

出版信息

Int J Clin Oncol. 2025 Apr;30(4):781-788. doi: 10.1007/s10147-025-02715-3. Epub 2025 Feb 14.

Abstract

BACKGROUND

Axitinib is a widely used tyrosine kinase inhibitor (TKI) in metastatic renal cell carcinoma (mRCC) treatment. Here, we analyzed the characteristics of patients who did not respond to axitinib and evaluated alternative options for their treatment.

METHODS

We retrospectively analyzed data for 449 patients with mRCC who were administered axitinib following another TKI as initial therapy. Patients with progressive disease (PD) at their first assessment were defined as showing early-PD. We analyzed the characteristics of patients at risk of early-PD and evaluated the relationship between the treatment following axitinib and their prognosis.

RESULTS

Early-PD was diagnosed in 102 patients, and was more common in those who had not undergone nephrectomy (p < 0.001), those treated with a TKI for a short period (p < 0.001), and those in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) poor risk category for mRCC (p < 0.001). Multivariate analysis showed that these were independent risk factors for early-PD (all p < 0.001). Of those with early-PD, 52 changed to next-line treatment. The progression-free survival periods were 5.5 (95% confidence interval (CI) 2.4-8.6) months for patients administered TKIs, 4.2 (95% CI 0.3-8.1) months for those on nivolumab, and 2.2 (1.8-2.6) months for those on mammalian target of rapamycin inhibitors (p = 0.030).

CONCLUSION

Patients who have not undergone nephrectomy, those previously treated with another TKI for a short period, and those in the IMDC poor risk category are more likely to experience early-PD when taking axitinib. Furthermore, TKIs are the best treatment for patients with early-PD who have previously been administered axitinib.

摘要

背景

阿昔替尼是转移性肾细胞癌(mRCC)治疗中广泛使用的酪氨酸激酶抑制剂(TKI)。在此,我们分析了对阿昔替尼无反应的患者特征,并评估了其治疗的替代方案。

方法

我们回顾性分析了449例mRCC患者的数据,这些患者在接受另一种TKI作为初始治疗后接受了阿昔替尼治疗。首次评估时疾病进展(PD)的患者被定义为早期PD。我们分析了有早期PD风险的患者特征,并评估了阿昔替尼治疗后的治疗与患者预后之间的关系。

结果

102例患者被诊断为早期PD,在未接受肾切除术的患者中更常见(p < 0.001),接受TKI治疗时间短的患者(p < 0.001),以及国际转移性肾细胞癌数据库联盟(IMDC)中mRCC风险较差类别的患者(p < 0.001)。多变量分析表明,这些是早期PD的独立风险因素(所有p < 0.001)。在那些早期PD患者中,52例改为二线治疗。接受TKI治疗的患者无进展生存期为5.5(95%置信区间(CI)2.4 - 8.6)个月,接受纳武单抗治疗的患者为4.2(95%CI 0.3 - 8.1)个月,接受雷帕霉素靶蛋白抑制剂治疗的患者为2.2(1.8 - 2.6)个月(p = 0.030)。

结论

未接受肾切除术的患者、先前接受另一种TKI治疗时间短的患者以及IMDC风险较差类别的患者在服用阿昔替尼时更有可能经历早期PD。此外,TKI是先前接受过阿昔替尼治疗的早期PD患者的最佳治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4985/11947068/544d7d97a10f/10147_2025_2715_Fig1_HTML.jpg

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