Safety,Efficacy, and Patient-Reported Health-Related Quality of Life and Symptom Burden with Nivolumab in Patients with Advanced Non–Small Cell Lung Cancer,Including Patients Aged 70 Years or Older or with Poor Performance Status (CheckMate 153)

IntroductionCheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials.MethodsPatients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal. The primary end point was the incidence of grade 3 to 5 select treatment-related adverse events (TRAEs).ResultsAmong 1426 treated patients, 556 (39%) were aged 70 years or older and 128 (9%) had an ECOG PS of 2. The median treatment duration was 3.2 months. Across subgroups and the overall population, the incidences of select grade 3 to 5 TRAEs (6%–9%) and grade 3 or 4 TRAEs (12%–14%) were similar. One grade 5 TRAE was documented. The median overall survival time was comparable in the overall population (9.1 months) and patients aged 70 years or older (10.3 months) but shorter in patients with an ECOG PS of 2 (4.0 months). Patient-reported outcomes generally improved.ConclusionsData from this large predominantly community-based study, which included patients aged 70 years or older and with an ECOG PS of 2, are consistent with registrational studies. As expected, the median overall survival for patients with an ECOG PS of 2 was lower than for the overall population but comparable with historical data.     

基于Markov模型的纳武利尤单抗治疗化疗后失败的进展期胃癌的成本效果分析

目的:评价近期在国内批准上市的纳武利尤单抗治疗化疗后失败的进展期胃癌的成本效果。方法:采用ATTRACTION-2临床试验所获数据(纳武利尤单抗组330例,安慰剂组163例),建立Markov模型模拟化疗失败后进展期胃癌的疾病过程。分析每组的成本、生命年(LY)以及质量调整生命年(QALY),然后计算增量成本效果比(ICER),并根据程序性细胞死亡配体1(PD-L1)的表达进行了亚组分析。运用敏感度分析对参数进一步评估,评价模型的稳定性。结果:PD-L1阳性的患者中,纳武利尤单抗组总健康产出值0.357QALY(0.526LY),总成本221171元;安慰剂组总健康产值0.251QALY(0.368LY),总成本40866元,纳武利尤单抗组相比安慰剂组的ICER为1700991元/QALY。PD-L1阴性的患者中,纳武利尤单抗组总健康产出值0.545QALY(0.845LY),总成本333195元;安慰剂组总健康产出值为0.403QALY(0.63LY),总成本为90285元,纳武利尤单抗组相比安慰剂组的ICER为1710634元/QALY。两亚组中纳武利尤单抗的ICER均大于意愿支付值(178980元)。概率敏感度分析显示,纳武利尤单抗具有成本效果性的概率为0。一元敏感度分析提示纳武利尤单抗的价格对结果影响最大。结论:在当前中国医疗保障角度下,纳武利尤单抗对比安慰剂在化疗失败的晚期胃癌患者治疗中不具有成本效果性,但是纳武利尤单抗可以为这些患者带来生存获益,通过开展慈善援助计划、纳入医保等措施可以提高其经济性。     

Safety,efficacy, and tolerability of immune checkpoint inhibitors in the treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a major cause of mortality worldwide with an increasing incidence due to escalating rates of obesity and non-alcoholic fatty liver disease. Unfortunately, a majority of patients with HCC present with advanced disease. The immune checkpoint inhibitor atezolizumab, a PD-L1 inhibitor, in combination with bevacizumab, anti-VEGF, has become the new standard of care for patients with advanced HCC after demonstrating improved overall and progression free survival over sorafenib. In this review, we discuss the evolving role of immune checkpoint inhibitors in the treatment of HCC and their safety, efficacy, and tolerability.     

Anti-PD1/PDL1 induced psoriasis

BackgroundImmune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported.MethodsWe present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy.ResultsA total of 5 patients were overall included (4 males, 1 female mean age 65.8 years). Among them, 3 were diagnosed with nonsmall cell lung cancer, 1 with papillary urothelial carcinoma, and 1 with squamous cell carcinoma of the tonsil. Of all, 3 patients were treated with anti-PD1 (1 with pembrolizumab, 2 with nivolumab), whereas the remaining 2 with anti-PDL1 (durvalumab). Only 1 out of 5 patients had active psoriatic lesions at the time of treatment initiation, 2 shared a past history of psoriasis, and 1 reported a strong related family history (3/5 siblings). Four out of 5 patients experienced guttate lesions, though the most severe exacerbation was noted in the durvalumab group. Four out of 5 patients managed to continue treatment after close dermatologic monitoring, whereas 1 patient under durvalumab was forced to treatment delays owing to the severity of the skin reactions. Skin rashes appeared in all patients after the fourth cycle of immunotherapy.ConclusionsBoth anti-PD1 and anti-PDL1 therapies can lead to psoriasis exacerbation although more severe flares were noted in patients treated with durvalumab. Not only personal but also related family history of psoriasis are significant risk factors and need to be outlined before treatment initiation. If such related history exists, strict skin surveillance can lead to the early diagnosis and treatment of any psoriatic exacerbations that could otherwise severely affect quality of life or even compromise therapeutic protocols and final prognosis.     

The 2017 complete overhaul of adjuvant therapies for high-risk melanoma and its consequences for staging and management of melanoma patients

The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C–IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018. Toxicity profiles are in line with the experience in advanced melanoma, i.e. favourable for the anti-PD1 agents and for D + T and problematic for ipilimumab. The 2017 outcomes are practice changing and put an end to the use of interferon (IFN) and ipilimumab. In countries with only access to IFN, its use can be restricted to patients with ulcerated melanoma, based on the individual patient data meta-analysis recently published. Because of the results of the Melanoma Sentinel Lymph node Trial-2 (MSLT-2) trial, completion lymph node dissection (CLND) will decrease sharply, leading to a lack of optimal prognostic information. Prognosis in sentinel node–positive stage IIIA/B patients is extremely heterogeneous with 5-year survival rates varying from 90% to 40% and depends mostly on the number of positive nodes identified by CLND. This information is crucial for clinical decision-making. How to guarantee optimal staging information needs to be discussed urgently. Further improvements of adjuvant therapies will have to address all these questions as well as the exploration of neoadjuvant use of active drugs and combination approaches. Important paradigm shifts in the management of high-risk melanoma patients are upon us.     

纳武利尤单抗联合替莫唑胺同步放疗治疗 老年晚期小细胞肺癌脑转移的疗效

目的 分析纳武利尤单抗联合替莫唑胺（temozolomide,TMZ）同步放疗治疗老年晚期小细胞肺癌（small cell lung cancer,SCLC）脑转移的疗效。方法 选择2017年1月至2020年12月于九江市第一人民医院治疗的72例老年晚期SCLC脑转移患者,根据随机数字表法将其分为两组,每组各36例。对照组患者采用TMZ同步放疗治疗,观察组患者采用纳武利尤单抗联合TMZ同步放疗。比较两组患者的临床疗效、血清肿瘤标志物水平、总生存（overall survival,OS）时间、无进展生存（progress free survival,PFS）时间、生存质量及不良反应。结果 观察组患者的疾病控制率显著高于对照组（P<0.05）;治疗后,观察组患者的血清胃泌素释放肽前体（progastrin releasing peptide,ProGRP）、神经元特异性烯醇化酶（neuron specific enolase,NSE）水平均显著低于对照组（P<0.05）,OS、PFS时间均显著长于对照组（P<0.05）,生存质量显著优于对照组（P<0.05）。两组患者的肝功能损害、消化道反应、血小板减少、白细胞减少、骨髓抑制发生率比较,差异均无统计学意义（P>0.05）。结论 老年晚期SCLC脑转移患者采用纳武利尤单抗联合TMZ同步放疗可缩小颅内病灶,降低ProGRP、NSE水平,延长患者生存期,提高患者生活质量,且安全可靠。