在免疫治療時代中轉移性腎細胞癌的治療

近年隨著免疫治療 (immunotherapy, IO) 與使用標靶治療 (target therapy) 的興起，轉移性腎細胞癌 (renal cell carcinoma, RCC) 的治療有了顯著變化。本研究旨在評估真實世界情境中轉移性腎細胞癌的治療順序與療效，並探討接受初預先 (upfront) 減積性腎臟切除手術(cytoreductive nephrectomy, CN) 患者的預後。研究使用TriNetX資料庫，蒐集2008年1月至2022年5月間，因為轉移性腎細胞癌，接受第一線全身性治療的患者。治療方式包括酪胺酸激?抑制劑(tyrosine kinase inhibitor, TKI) 單藥治療、ipilimumab + nivolumab治療，以及pembrolizumab + axitinib治療。共有4,183名患者接受TKI單藥治療，1,555名接受ipilimumab + nivolumab治療，559名接受pembrolizumab + axitinib治療。接受TKI治療的患者，整體存活期中位數為42.2個月，ipilimumab + nivolumab為39.7個月，pembrolizumab + axitinib組則尚未達到整體存活期的中位數，跟TKI組比起來，pembrolizumab + axitinib組有更高的存活率 (p = 0.016)，但是TKI組與ipilimumab + nivolumab組別比較則未顯現出差異，雖然接受ipilimumab + nivolumab治療的病患較高的機率有共病與遠端轉移。接受預先減積性腎臟切除手術的患者，與沒有接受手術的患者比較，有較好的總體存活率 (overall survival, OS)，無論患者接受標靶治療 (hazard ratio 0.722, 95% confidence interval 0.67-0.73, p < 0.001) 或是免疫治療 (hazard ratio 0.651, 95% confidence interval 0.59-0.71, p < 0.001)。在多變數分析 (multivariate analysis) 中，也顯示預先減積性腎臟切除手術與較高的整體存活期相關。在真實世界的臨床實踐中，轉移性腎細胞癌患者有越來越多第一線使用免疫療法的趨勢。相較於接受TKI單藥治療或ipilimumab + nivolumab治療，患者接受axitinib + pembrolizumab治療有較好的整體存活期。此外，在免疫治療時代中，減積性腎切除手術仍然具有其臨床價值。

With the introduction of immunotherapy and target therapy, the treatment landscape for metastatic renal cell carcinoma changed a lot in the last few years. This study aimed to assess the treatment sequences and outcomes for metastatic renal cell carcinoma in a real-world setting and evaluate the outcomes of metastatic renal cell carcinoma patients treated with upfront cytoreductive nephrectomy. We enrolled patients with metastatic renal cell carcinoma who received first-line systemic treatment with tyrosin kinase inhibitors monotherapy, ipilimumab plus nivolumab, or pembrolizumab plus axitinib between January 2008 and May 2022 on the database of TriNetX network. Totally, 4183 received tyrosine kinase inhibitor monotherapy, 1555 received ipilimumab plus nivolumab, and 559 received axitinib plus pembrolizumab. Median overall survival was 42.2 months for the tyrosine kinase inhibitor monotherapy cohort, 39.7 months for the ipilimumab plus nivolumab cohort, and not reached for the pembrolizumab plus axitinib cohort. In comparison with the tyrosine kinase inhibitor monotherapy cohort, patients in the pembrolizumab plus axitinib cohort showed survival benefit (p = 0.016) in overall survival, but not the case in the ipilimumab plus nivolumab cohort. Those receiving upfront cytoreductive nephrectomy showed survival advantages with either tyrosine kinase inhibitor (hazard ratio 0.722, 95% confidence interval 0.67-0.73, p < 0.001) or immune checkpoint inhibitors (hazard ratio 0.651, 95% confidence interval 0.59-0.71, p < 0.001). In multivariable analysis, upfront cytoreductive nephrectomy was a factor for improved OS in both cohorts. There was a trend toward using first-line immuno-oncology based therapy for patients with metastatic renal cell carcinoma in a real-world practice. Axitinib plus pembrolizumuab cohort had survival benefits over tyrosine kinase inhibitor and ipilimumab plus nivolumab cohorts. Cytoreductive nephrectomy still has a role in the era of immunotherapy.