Hyperprogressive Disease in Patients With Urothelial Carcinoma or Renal Cell Carcinoma Treated With PD-1/PD-L1 Inhibitors

BackgroundA rapid progression pattern called hyperprogressive disease (HPD) has been observed during early cycles of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor therapy. Data regarding HPD in patients with genitourinary cancer are limited.Patients and MethodsWe included 203 patients with genitourinary cancer treated with PD-1/PD-L1 inhibitors between February 2015 and June 2018. HPD was defined as a greater than 50% increase in tumor burden, greater than 2-fold increase in tumor growth rate, or development of extensive (10 or more) new lesions.ResultsPatients (n = 102) with renal cell carcinoma (RCC) and patients (n = 101) with urothelial carcinoma (UC) were included. HPD was observed in 13 (6.4%) patients. The median overall survival for patients with progressive disease and HPD was 7.3 months and 3.5 months, respectively. HPD occurred more frequently in patients with UC than in those with RCC (11.9% vs. 0.9%; P = .01). Multivariate analysis showed that UC and creatinine above 1.2 mg/dL were independent predictive factors for HPD. A 30% increase in lymphocyte number following PD-1/PD-L1 inhibitor treatment was a negative predictor of HPD. The incidence of HPD in patients with UC treated with paclitaxel-based chemotherapy was one-third of those treated with PD-1/PD-L1 inhibitors.ConclusionHPD developed predominantly in patients with UC, and the incidence of HPD in patients with RCC was negligible. Treatment with PD-1/PD-L1 inhibitors should be prescribed with caution in patients with UC and creatinine above 1.2 mg/dL.     

非小细胞肺癌免疫治疗之假性进展和超进展

随着医疗技术日益发展,肿瘤治疗取得了显著的进步。其中,免疫治疗为肺癌患者开辟了一条全新的道路,其代表药物——PD-1/PD-L1抑制剂的应用显著延长了部分非小细胞肺癌(NSCLC)患者的整体生存率,但在使用过程中也可能出现假性进展或超进展(HPD)现象,其发生机制尚未明确。本文将对假性进展和HPD的定义、发生机制以及可供参考的生物标志物及鉴别方法进行系统地综述。     

Immune response evaluation criteria in solid tumors for assessment of atypical responses after immunotherapy

In 2017, immune response evaluation criteria in solid tumors (iRECIST) were introduced to validate radiologic and clinical interpretations and to better analyze tumor’s response to immunotherapy, considering the different time of following and response, between this new therapy compared to the standard one. However, even if the iRECIST are worldwide accepted, to date, different aspects should be better underlined and well reported, especially in clinical practice. Clinical experience has demonstrated that in a non-negligible percentage of patients, it is challenging to determine the correct category of response (stable disease, progression disease, partial or complete response), and consequently, to define which is the best management for those patients. Approaching radiological response in patients who underwent immunotherapy, a new uncommon kind of target lesions behavior was found. This phenomenon is mainly due to the different mechanisms of action of immunotherapeutic drug. Therefore, new groups of response have been described in clinical practice, defined as “atypical responses,” and categorized into three new groups: pseudoprogression, hyperprogression, and dissociated response. This review summarizes and reports these patterns, helping clinicians and radiologists get used to atypical responses, in order to identify patients that respond best to treatment.     

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report

In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907–910, 2020     

浅谈胆道恶性肿瘤免疫治疗面临的挑战：治疗抵抗及超进展

免疫治疗为胆道恶性肿瘤（BTC），特别是晚期患者提供了新的治疗方案，durvalumab以其可接受的药物毒性及显著的预后改善作用成为晚期BTC的一线治疗方案。不可忽视的是，免疫治疗为BTC患者带来获益的同时面临着两项挑战，即治疗抵抗及超进展，二者发生率较高，影响免疫治疗疗效甚至加速肿瘤进展。笔者从二者发生机制入手，梳理其中免疫相关生物学过程，以此为依据制定方案应对免疫治疗抵抗及超进展，以期帮助提升BTC免疫治疗疗效、完善胆道外科综合治疗策略。