Kwok Christopher, Khorasanchi Adam, Psutka Sarah P, Hinkley Megan, Dason Shawn, Sundi Debasish, Yang Yuanquan, Yang Yajing, Verschraegen Claire, Gross Evan E, Orcutt Delaney, Yin Ming
Department of Pharmacy, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.
Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, United States.
Front Oncol. 2023 Jul 27;13:1231831. doi: 10.3389/fonc.2023.1231831. eCollection 2023.
The optimal treatment for metastatic renal cell carcinoma (mRCC) patients who have progressed after both immune checkpoint inhibitor (ICI) and VEGFR tyrosine kinase inhibitor (TKI) remains uncertain. Lenvatinib and everolimus (LE) are frequently used in combination as salvage therapy because of their different antitumor mechanisms, but efficacy and toxicity data in this setting are lacking.
We retrospectively reviewed charts from two academic centers for 71 adult mRCC patients who received LE after prior ICI and TKI exposure. We evaluated patient demographics, histology, International mRCC Database Consortium (IMDC) risk group, treatment history, and toxicity details. Outcomes of interest included objective response rate (ORR), time to treatment failure (TTF), overall survival (OS), ≥grade 3 toxicities, and schedule or dosage changes, which were evaluated using descriptive statistics, chi-square test, Cox proportional hazards model, and the Kaplan-Meier method.
The median age was 64 (range 31-84). Most patients had clear cell histology (84.5%) and had undergone nephrectomy (80.3%). IMDC risks were favorable (19.7%), intermediate (int) (66.2%), poor (11.3%), and unknown (2.8%). The average ORR was 26.8%, while the median TTF was 5.5 months (95% confidence interval [CI], 3.5-7.6) and the median OS was 9 months (95% CI, 7.6-12.9). Intermediate and poor IMDC risks were independently associated with a significantly worse TTF compared to favorable risk (hazard ratio (HR), 3.03, 95% CI, 1.18-7.79), as was ≥4L treatment 2L/3L treatment (HR, 2.02, 95% CI, 1.08-3.8). Of the 71 patients, 57.7% had ≥grade 3 adverse events, 60% had treatment interruption, 44.3% had dose reduction, and 21% stopped treatment due to intolerance.
LE therapy is feasible but has modest efficacies following ICI/TKI treatment. Patients with favorable risk or treated earlier may have a better treatment response. These observations need to be confirmed in prospective studies.
对于在免疫检查点抑制剂（ICI）和VEGFR酪氨酸激酶抑制剂（TKI）治疗后病情进展的转移性肾细胞癌（mRCC）患者，最佳治疗方案仍不确定。乐伐替尼和依维莫司（LE）因其不同的抗肿瘤机制，常联合用作挽救治疗，但这一情况下的疗效和毒性数据尚缺乏。
我们回顾性分析了两个学术中心71例成年mRCC患者的病历，这些患者在先前接受ICI和TKI治疗后接受了LE治疗。我们评估了患者的人口统计学特征、组织学类型、国际mRCC数据库联盟（IMDC）风险组、治疗史和毒性细节。感兴趣的结局包括客观缓解率（ORR）、治疗失败时间（TTF）、总生存期（OS）、≥3级毒性反应以及治疗方案或剂量的改变，使用描述性统计、卡方检验、Cox比例风险模型和Kaplan-Meier方法进行评估。
中位年龄为64岁（范围31 - 84岁）。大多数患者为透明细胞组织学类型（84.5%），且已接受肾切除术（80.3%）。IMDC风险为低危（19.7%）、中危（int）（66.2%）、高危（11.3%）和未知（2.8%）。平均ORR为26.8%，而中位TTF为5.5个月（95%置信区间[CI]，3.5 - 7.6），中位OS为9个月（95% CI，7.6 - 12.9）。与低危风险相比，IMDC中危和高危风险独立与显著更差的TTF相关（风险比[HR]，3.03，95% CI，1.18 - 7.79），≥4线治疗与2线/3线治疗相比也是如此（HR，2.02，95% CI，1.08 - 3.8）。71例患者中，57.7%发生≥3级不良事件，60%有治疗中断，44.3%有剂量减少，21%因不耐受停止治疗。
LE治疗是可行的，但在ICI/TKI治疗后疗效一般。低危风险或早期接受治疗的患者可能有更好的治疗反应。这些观察结果需要在前瞻性研究中得到证实。
