Cancer-specific mortality in patients with non-metastatic renal cell carcinoma who have undergone a nephrectomy and are eligible for adjuvant pembrolizumab

IF 3 3区 医学 Q2 ONCOLOGY
Rocco S. Flammia , Benedikt Hoeh , Lukas Hohenhorst , Gabriele Sorce , Francesco Chierigo , Andrea Panunzio , Zhe Tian , Fred Saad , Costantino Leonardo , Alberto Briganti , Alessandro Antonelli , Carlo Terrone , Shahrokh F. Shariat , Markus Graefen , Felix K.H. Chun , Francesco Montorsi , Michele Gallucci , Pierre I. Karakiewicz
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引用次数: 2

Abstract

Background

Data in patients with malignant melanoma, who have been previously treated with pembrolizumab as adjuvant therapy, show a reduction in pembrolizumab efficacy upon rechallenge. We examined this scenario in patients with non-metastatic renal cell carcinoma (RCC) eligible for adjuvant pembrolizumab after nephrectomy. We hypothesized that a proportion of such patients will either require re-treatment with pembrolizumab upon metastatic progression prior to cancer-specific mortality (CSM) or die from other cause mortality (OCM).

Materials and methods

We identified within the SEER database 10,635 patients, between 2004 and 2017, with a diagnosis of non-metastatic intermediate-high and high risk RCC, who had undergone nephrectomy and fulfilled criteria for enrollment in KEYNOTE-564. Kaplan-Meier analyses addressed overall survival (OS), CSM and OCM.

Results

9,825 (92.4%) of the 10,635 patients had intermediate-high risk RCC and 9,456 (88.9%) underwent radical nephrectomy. Additionally, 760 (7.1%) harbored sarcomatoid features. In Kaplan-Meier analyses, median OS was 9.8 (9.1–11.4) years. At 10-years of follow-up, CSM rate was 36% and OCM rate was 22%.

Conclusions

Based on CSM, our observations indicate that by 10-years of follow-up 36% of patients treated with adjuvant pembrolizumab will require a rechallenge, in a setting where a checkpoint inhibitor may have reduced efficacy. Moreover, at 10-years of follow-up, 22% of patients with RCC, previously treated with adjuvant pembrolizumab, will die of other causes. These percentages should be strongly considered prior to routine use of adjuvant pembrolizumab, especially given an OS benefit has not been proven.

非转移性肾细胞癌患者接受肾切除术后的癌症特异性死亡率,并有资格使用辅助派姆单抗
背景:在恶性黑色素瘤患者中,曾接受过派姆单抗辅助治疗的数据显示,再次挑战后派姆单抗的疗效降低。我们在非转移性肾细胞癌(RCC)患者中检查了这种情况,这些患者在肾切除术后符合使用辅助派姆单抗的条件。我们假设,这类患者中有一部分在转移进展后,在癌症特异性死亡(CSM)之前或死于其他原因死亡(OCM)之前,需要再次使用派姆单抗治疗。材料和方法在2004年至2017年期间,我们在SEER数据库中确定了10,635例诊断为非转移性中、高、高风险RCC的患者,这些患者接受了肾切除术,符合KEYNOTE-564的入组标准。Kaplan-Meier分析了总生存期(OS)、CSM和OCM。结果10635例患者中,9825例(92.4%)为中高危肾细胞癌,9456例(88.9%)行根治性肾切除术。此外,760例(7.1%)伴有肉瘤样特征。在Kaplan-Meier分析中,中位OS为9.8(9.1-11.4)年。随访10年,CSM率为36%,OCM率为22%。基于CSM,我们的观察表明,在检查点抑制剂可能降低疗效的情况下,经过10年的随访,36%接受辅助派姆单抗治疗的患者将需要重新挑战。此外,在10年的随访中,22%之前接受过辅助派姆单抗治疗的RCC患者将死于其他原因。在常规使用辅助派姆单抗之前,应该强烈考虑这些百分比,特别是考虑到OS益处尚未得到证实。
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来源期刊
Seminars in oncology
Seminars in oncology 医学-肿瘤学
CiteScore
6.60
自引率
0.00%
发文量
58
审稿时长
104 days
期刊介绍: Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.
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