目的:辅助pembrolizumab显著改善肾细胞癌(RCC)的总生存期(OS),但是关于序贯治疗的真实数据很少。我们试图评估基于辅助免疫肿瘤学(IO)的方案后一线(1L)全身治疗的临床结果。
方法:在29个国际机构中进行了一项回顾性研究,包括接受IO辅助治疗的复发性RCC患者。主要终点是使用Kaplan-Meier方法估计的1L全身治疗的无进展生存期(PFS)。按1L全身治疗类型对临床结果进行预先计划的亚分析,复发时机,和国际转移性RCC数据库联盟(IMDC)风险组。治疗相关的不良事件导致治疗中断,剂量减少,或皮质类固醇的使用进行了评估。
■共纳入94例患者。大多数人接受了佐剂pembrolizumab(n=37,39%),阿替珠单抗(n=28,30%),或nivolumab+ipilimumab(n=15,16%)。该队列包括49名(52%)患者,他们在最后一次辅助IO剂量的3个月内复发,而45(48%)在3个月后复发。在<3个月时复发的肿瘤(10/49,20%)的骨转移明显高于在>3个月时复发的肿瘤(1/45,2.2%;p=0.008)。大多数患者接受了1L血管内皮生长因子靶向治疗(VEGF-TT;n=37,39%),IO+VEGF-TT(n=26,28%),或IO+IO(n=12,13%)。其余患者接受局部治疗。1L全身治疗队列的中位随访时间为15个月。18个月的PFS和OS率分别为45%(95%置信区间[CI]:34-60)和85%(95%CI:75-95),分别。32例(42%)患者发生治疗相关不良事件,包括皮肤毒性(n=7,9.2%)。疲劳(n=6,7.9%),和腹泻/结肠炎(n=4,5.3%)。局限性包括从大型学术中心选择患者和短随访期。
结论:在辅助IO治疗后复发性肾癌患者的一部分对全身治疗有反应,包括VEGF-TT和基于IO的方案。值得注意的是,在这种情况下,高危疾病患者可能从VEGF-TT中获得比IO治疗更多的获益.利用放射照相工具和基于生物标记物的液体活检的未来方法是必要的,以检测隐匿性转移性疾病并确定辅助IO治疗的候选患者。
结果:辅助派姆单抗显著改善肾细胞癌(RCC)的总生存率。关于辅助免疫疗法后RCC肿瘤复发的临床结果的数据有限。在这项研究中,我们发现,在不同的治疗方案中,患者对随后的全身治疗有反应.
OBJECTIVE: Adjuvant pembrolizumab significantly improved overall survival (OS) in renal cell carcinoma (RCC), but real-world data on sequential treatment are scarce. We sought to evaluate the clinical outcomes of first-line (1L) systemic therapy following adjuvant immune oncology (IO)-based regimens.
METHODS: A retrospective study including patients with recurrent RCC following adjuvant IO across 29 international institutions was conducted. The primary endpoint was progression-free survival (PFS) on 1L systemic therapy estimated using the Kaplan-Meier method. Preplanned subanalyses of clinical outcomes by type of 1L systemic therapy, recurrence timing, and International Metastatic RCC Database Consortium (IMDC) risk groups were performed. Treatment-related adverse events leading to treatment discontinuation, dose reduction, or corticosteroid use were assessed.
UNASSIGNED: A total of 94 patients were included. Most received adjuvant pembrolizumab (n = 37, 39%), atezolizumab (n = 28, 30%), or nivolumab + ipilimumab (n = 15, 16%). The cohort included 49 (52%) patients who had recurrence within 3 mo of the last adjuvant IO dose, whereas 45 (48%) recurred beyond 3 mo. Bone metastases were significantly higher in tumors recurring at <3 mo (10/49, 20%) than those recurring at >3 mo (1/45, 2.2%; p = 0.008). Most patients received 1L vascular endothelial growth factor-targeted therapy (VEGF-TT; n = 37, 39%), IO + VEGF-TT (n = 26, 28%), or IO + IO (n = 12, 13%). The remaining underwent local therapy. The median follow-up for the 1L systemic therapy cohort was 15 mo. The 18-mo PFS and OS rates were 45% (95% confidence interval [CI]: 34-60) and 85% (95% CI: 75-95), respectively. Treatment-related adverse events occurred in 32 (42%) patients and included skin toxicity (n = 7, 9.2%), fatigue (n = 6, 7.9%), and diarrhea/colitis (n = 4, 5.3%). Limitations included selecting patients from large academic centers and the short follow-up period.
CONCLUSIONS: A subset of patients with recurrent RCC following adjuvant IO respond to systemic therapies, including VEGF-TT and IO-based regimens. Notably, patients with favorable-risk disease may derive more benefit from VEGF-TT than from IO therapies in this setting. Future approaches utilizing radiographic tools and biomarker-based liquid biopsies are warranted to detect occult metastatic disease and identify candidate patients for adjuvant IO therapy.
RESULTS: Adjuvant pembrolizumab significantly improved overall survival in renal cell carcinoma (RCC). There are limited data on clinical outcomes after the recurrence of RCC tumors following adjuvant immunotherapy. In this study, we find that patients respond to subsequent systemic therapies across different treatment options.