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根据发表在《柳叶刀》杂志上的随机第3期KEYNOTE-048研究的结果，将Pembrolizumab联合铂类化学疗法联合治疗对于复发或转移性头颈部鳞状细胞癌似乎是一种安全有效的一线治疗。 根据安全性和有效性数据，研究人员还认为，用派姆单抗（Keytruda，Merck）进行一线单药治疗适合PD-L1阳性复发或转移性HNSCC患者。  “我相信这项研究的结果已经改变护理标准，” 芭芭拉Burtness医师，医学院和耶鲁大学癌症中心的耶鲁大学医学院教授，HemOnc今天编委，告诉Healio。“ FDA在6月的第一线批准了pembrolizumab，因此，PD-L1表达患者的pembrolizumab单药疗法以及所有患者的pembrolizumab联合化疗现在已成为治疗的标准。” Burtness和同事写道，在HNSCC中将化疗与免疫检查点抑制剂联合使用是有意义的，因为它破坏了肿瘤结构，从而减少了免疫排斥，导致抗原脱落，并促进了疾病的快速控制。 研究人员进行了本试验，以确定在复发性或转移性HNSCC患者中，与EGFR抑制剂西妥昔单抗（Erbitux，Eli Lilly）相比，PD-1抑制剂pembrolizumab单药治疗或联合化疗是否能改善OS。 研究人员将882例先前未接受过治疗的复发或转移性HNSCC患者随机分配为pembrolizumab单药治疗（n = 301），pembrolizumab联合卡铂或顺铂和5-FU（n = 281）或西妥昔单抗联合卡铂或顺铂和5-FU（n = 300）。 在所有患者中，有754名（85％）的PD-L1合并阳性评分（CPS）为1或更高，而381名（43％）的CPS为20或更高。 OS和PFS是研究的主要终点。次要终点包括安全性和耐受性。 pembrolizumab单药治疗组中位随访时间为11.5个月，pembrolizumab化疗组为13个月，西妥昔单抗化疗组为10.7个月。 第二次中期分析的结果显示，在CPS为20或更高的患者（中位14.9个月vs. 10.7个月； HR = 0.61； 95％CI，0.45-0.83）中，单独使用pembrolizumab与西妥昔单抗联合化疗相比改善了OS。 CPS为1或更高（中位数为12.3个月vs. 10.3个月； HR = 0.78； 95％CI，0.64-0.96）。在所有人群中，使用派姆单抗单药治疗的OS均不低于西妥昔单抗和化疗的OS（中位值，分别为11.6个月和10.7个月； HR = 0.85； 95％CI，0.71-1.03）。 研究人员在第二次中期分析中观察到，在所有患者中，使用派姆单抗联合化疗与西妥昔单抗和化疗相比，OS显着改善（中位，13个月vs. 10.7个月； HR = 0.77； 95％CI，0.63-0.93）。他们还报告说，在最终分析中，CPS为20或更高（中位14.7个月vs. 11个月； HR = 0.6； 95％CI，0.45-0.82）和CPS为1或更高的患者在OS方面具有显着的获益。 （13.6个月vs.10.4个月； HR = 0.65； 95％CI，0.53-0.8）。 Read more...

Novartis has confirmed in an email to The Center for Biosimilars® that it has launched Sandoz’s pegfilgrastim biosimilar, Ziextenzo, in the United States. According to Novartis, the wholesale acquisition cost (WAC) for Ziextenzo is $3925, or an approximate 37% discount off the WAC for the reference product, Amgen’s Neulasta. The discount for Ziextenzo is deeper than those initially offered for competitor biosimilars; when Coherus BioSciences launched its biosimilar, Udenyca, in the US market in January of this year, it did so at a list price of $4175 per unit, or a 33% discount. That price matched that of Mylan and Biocon’s Fulphila, which launched in July of 2018. It remains to be seen how much of an impact the additional discount will make for the new biosimilar contender. In May of this year, UnitedHealthcare indicated in a network bulletin that it will prefer the brand-name pegfilgrastim over biosimilar options. In that bulletin, UnitedHealthcare said that the use of Neulasta Onpro (a presentation of the pegfilgrastim product in an on-body injector device) or Neulasta in a vial would be required before use of one of the then-available biosimilars would be allowed. The biosimilar was approved by the FDA on November 5, after Sandoz submitted data from a pivotal pharmacokinetic (PK) and pharmacodynamic study. The study was a single-dose, 3-period crossover study that compared the biosimilar with the US-sourced and EU-sourced reference pegfilgrastim, and it compared the US and EU references. The study sought to address the high intersubject variability (ISV) linked to target-mediated clearance with pegfilgrastim; the 3-way crossover design was intended to address ISV and to provide a bridge between the EU and US reference pegfilgrastim products. A previous PK study was conducted in healthy volunteers, and the biosimilar has also been studied in phase 3 clinical trials (PROTECT-1 and PROTECT-2) in patients undergoing chemotherapy. The biosimilar is also approved in the European Union, where it was authorized in January of this year. Article Source: https://www.centerforbiosimilars.com/news/novartis-confirms-it-has-launched-biosimilar-pegfilgrastim-ziextenzo-in-the-united-states

根据C HEST发表的系统评价和荟萃分析，全球超过三分之一的慢性阻塞性肺病（COPD）患者可能患有骨质疏松症。 “骨质疏松症相关骨折与慢性阻塞性肺病的几种不良健康结果相关，包括住院率和死亡率增加，肺功能下降和生活质量下降。因此，在过去十年中，对这一研究领域的兴趣不断增加，导致出版了大量研究，调查了慢性阻塞性肺病 骨质疏松症的患病率和危险因素，“研究人员写道。 对于这项系统评价和荟萃分析，研究人员纳入了58项研究，涉及8,753例慢性阻塞性肺病患者。他们发现，慢性阻塞性肺病患者的全球骨质疏松症患病率为38％（95％CI，34-43）。值得注意的是，慢性阻塞性肺病患者的骨质疏松症患病率在世界五个地区没有差异，包括美洲，东地中海，欧洲，东南亚和西太平洋地区（P = .49）。 此外，结果显示，患有和未患慢性阻塞性肺病的患者骨质疏松症的可能性几乎高出三倍（调整后的合并OR = 2.83; 95％CI，2-4.03）。 对于慢性阻塞性肺病患者，低骨密度或骨质疏松症的危险因素包括较低的BMI和较低的无脂肪质量，两项研究分析显示BMI低于18.5 kg / m 2与风险增加4倍有关。骨质疏松症（OR = 4.26; 95％CI，1.07-16.99）。此外，七项研究和两项研究的荟萃分析显示，骨质疏松症风险降低，BMI增加1 kg / m 2（OR = 0.8; 95％CI，0.76-0.85）和1 kg / m 2增加无脂肪量（OR = 0.64; 95％CI，0.49-0.83）。肌肉减少症的存在还与慢性阻塞性肺病患者患骨质疏松症的可能性增加相关（OR = 3.65; 95％CI，1.45-9.16）。 “这项系统评价和荟萃分析显示，骨质疏松症是全球慢性阻塞性肺病患者的一种常见合并症。低体重指数和低肌肉质量与这种增加的患病率相关。研究人员写道，应该在早期通过筛查确定患有骨质疏松症高风险慢性阻塞性肺病的个体，并且应该在肺病的早期阶段实施旨在改善或控制骨质疏松症危险因素的策略。- 梅丽莎福斯特 文章来源： https://www.healio.com/pulmonology/copd/news/online/%7B5f24b468-9ff3-468a-ae5c-bb4a991dcb7b%7D/osteoporosis-prevalent-in-patients-with-copd?utm_source=selligent&utm_medium=email&utm_campaign=pulmonology%20news&m_bt=3471879957865

The U.S. Food and Drug Administration (FDA) has approved Nityr (nitisinone tablets) for the hereditary tyrosinemia type 1 (HT-1), a rare metabolic disorder. The drug is to be taken in combination with dietary restriction of tyrosine and phenylalanine. HT- I is due to a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). The absence of FAH leads to an accumulation of toxic metabolic products as the body is unable to properly breakdown tyrosine. Nitisinone inhibits 4-hydroxyphenylpyruvate dioxygenase so that toxic by-products of tyrosine do not accumulate in the body. Nityr is the second drug approved for HT-1 patients. Another formulation of nitisinone, Orfadin, had been available for HT-1 for several years and comes in capsule and oral suspension form. The approval of Nityr provides additional treatment options for people with HT-1. Unlike Orfadin, Nityr does not require refrigeration and can be taken with or without food. “The FDA approval of Nityr for HT-1, is an exciting new treatment option for patients in the United States,” said Jon Miller, President of the Network of Tyrosinemia Advocates (NOTA) in a news release. “Since this new treatment is a small tablet and does not need refrigeration, it may offer convenience and a better quality of life to patients and families who struggle with the debilitating effects of HT-1. Cycle Pharmaceuticals has taken an innovative approach to help address unmet needs and I hope this will be an incentive for pharmaceutical companies to further invest and innovate in HT-1 treatments and support.” "Cycle Pharmaceuticals has interpreted the modern health needs of HT-1 patients and caregivers, by developing a treatment that may improve their quality of life. Nityr is the first milestone in the long-term engagement of Cycle Pharmaceuticals with the HT-1 community. We look forward to working with physicians, caregivers and the patient community to help HT-1 patients benefit from the developments that Nityr brings," said Antonio Benedetti, CEO, Cycle Pharmaceuticals. Nitry tablets are available 2 mg, 5 mg and 10 mg tablets that can be dissolved in water for younger patients, if necessary. Article Source: https://www.raredr.com/news/fda-approves-nityr

The combination of pembrolizumab plus dabrafenib and trametinib as first-line treatment for BRAF-mutated melanomashowed antitumor activity, but high rates of grade 3-5 treatment-related adverse events, according to results from the phase 2 KEYNOTE-022 trial presented at the ESMO 2018 Congress in Munich, Germany.1 The combination of pembrolizumab plus the BRAF inhibitors dabrafenib and trametinib showed promising antitumor activity in the phase 1 portion of the KEYNOTE-022 trial. This report was of the results from the phase 2 portion. The double-blind, phase 2 KEYNOTE-022 trial randomly assigned 120 patients with treatment-naïve stage III or IV melanoma harboring a BRAFV600E/Kmutation to receive pembrolizumab plus dabrafenib and trametinib or placebo plus dabrafenib and trametinib. The primary endpoint was progression-free survival (PFS) and the secondary endpoints included objective response rate (ORR), duration of response (DoR), time to response, and overall survival (OS). The ORR was 63% with pembrolizumab plus dabrafenib and trametinib compared with 72% with the BRAF inhibitors alone, with complete response rates of 18% and 13%, respectively. The median time to response was similar between arms at 2.8 months. During a median follow-up of 9.6 months, there was a trend toward prolonged PFS with the pembrolizumab combination, but it was not significant based on prespecified parameters that required a hazard ratio (HR) of 0.62 or less. The median PFS with the pembrolizumab combination was 16 months (95% CI, 8.6-21.5 months) compared with 10.3 months (95% CI, 7.0-15.6 months) with dabrafenib plus trametinib alone, resulting in an HR of 0.66 (P = .043). The 12-month PFS was 59% and 45% with the pembrolizumab combination or the BRAF inhibitors alone, respectively. The median DoR was longer with the pembrolizumab combination at 18.7 months (range, 1.9+ to 22.1 months) compared with 12.5 months (range, 2.1-19.5+ months) with dabrafenib plus trametinib. Responses lasting at least 18 months was more common with pembrolizumab, occurring in 60% of patients compared with 28% of patients receiving only the BRAF inhibitors. The 12-month OS was 80% with the pembrolizumab combination compared with 73% with dabrafenib plus trametinib. There were similar rates of any grade treatment-related adverse events (TRAEs), with 95% and 93% reported in the pembrolizumab combination and BRAF inhibitor only arms, respectively. Grade 3 to 5 TRAEs, however, occurred more frequently in the pembrolizumab combination arm at 58% compared with 27% in the dabrafenib plus trametinib arm. The discontinuation rate due to TRAEs was 40% and 20% in the pembrolizumab combination and dabrafenib plus trametinib arms, respectively. Common grade 3 to 5 TRAEs, which occurred in at least 5% of patients, included pyrexia, elevated ALT and/or AST, increased GGT, rash, and neutropenia. There was a death in the pembrolizumab arm caused by pneumonitis, which was deemed treatment-related. Immune-related AEs occurred in 43% of patients in the pembrolizumab group compared with 13% of patients in the BRAF inhibitor only group. The most common immune-related AEs were pneumonitis, hypothyroidism, skin disorders, hyperthyroidism, and uveitis. The authors concluded that the pembrolizumab combination “demonstrated numerically longer PFS and DoR and a higher rate of grade 3-5 TRAEs in patients with treatment-naïve BRAFV600E/K-mutant advanced melanoma.” Read more of Cancer Therapy Advisor's coverage of the ESMO 2018 meeting by visiting the conference page. Reference 1. Ascierto PA, Dummer R, et al. KEYNOTE-022 Part 3: Phase 2 randomized study of 1L dabrafenib (D) and trametinib (T) plus pembrolizumab (Pembro) or placebo (PBO) for BRAF-mutant advanced melanoma. Presented at: ESMO 2018 Congress; Munich, Germany: October 19-23, 2018. Abstract 1244O. Article Source: https://www.cancertherapyadvisor.com/esmo-2018/melanoma-pembrolizumab-dabrafenib-trametinib-shows-efficacy-adverse-effect-risk/article/809104/

Childbirth rates among women who survived Hodgkin lymphoma have improved and are now similar to those of the general population, according to study results conducted in Sweden and published in Journal of Clinical Oncology. “Historically, treatments for Hodgkin lymphoma with the potential to cure have had negative effects on fertility,” Caroline E. Weibull,applied biostatistician and PhD student at Karolinska Institutet in Stockholm, and colleagues wrote. “Irradiation to the pelvic region; alkylating agents; and the mechlorethamine, vincristine, procarbazine and prednisone (MOPP) regimen are particularly gonadotoxic.” Developments in treatment have lessened the effects of therapy on fertility. “Previous register-based studies evaluating childbirth patterns have indicated a lower number of children born to patients with Hodgkin lymphoma than comparators but have not assessed childbearing by currently used treatments in a population-based setting,” Weibull and colleagues wrote. The researchers used Swedish registers to identify 449 women who were diagnosed with Hodgkin lymphoma between 1992 and 2009, all of whom were in remission 9 months after diagnosis. The researchers matched these survivors by age and calendar year to 2,210 women in the general population and calculated the rates of first postdiagnosis birth. Overall, 22% of survivors who did not relapse had a child during follow-up. The rate of first childbirth among patients increased from 40.2 per 1,000 person-years during the period between 1992 and 1997 to 69.7 per 1,000 person-years during 2004 to 2009. Women who were diagnosed between 2004 and 2009 had a cumulative probability of childbirth similar to that of the general population. There were no observed differences between patients and the general population at 3 years after diagnosis, regardless of patients’ stage or treatment. During the first 3 years, however, patients who underwent six to eight courses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone had a lower rate of childbirth than the general population (HR = 0.23; 95% CI, 0.06-0.94). The same was true of patients who received six to eight courses of chemotherapy and radiotherapy (HR = 0.21; 95% CI, 0.07-0.65). “The increase of childbirth rates over calendar time likely has a multifactorial explanation, reecting reduced toxicity in Hodgkin lymphoma treatment but also changes in attitudes and counseling,” Weibull and colleagues wrote. “The good childbearing potentialamong contemporarily treated patients, as well as the safety of a pregnancy after Hodgkin lymphoma (with no increased risk of relapse for the women and reports of good health for children), needs to be communicated to patients, because it can relieve unnecessary anxiety and concern.” Article Source: https://www.healio.com/hematology-oncology/lymphoma/news/in-the-journals/8eb3fbf0-0524-4ef7-a6c5-0ad2a56f9fb2/childbirth-rates-among-hodgkin-lymphoma-survivors-match-the-general-population

背景 卡非佐米是一种选择性且不可逆的蛋白酶体抑制剂，被批准用于多发性骨髓瘤患者，这些患者先前接受过多种治疗方法的治疗。它在多发性骨髓瘤患者中表现出强大的活性，既可以作为单一疗法，也可以与其他抗骨髓瘤药物联合使用。来自ARROW研究的中期分析比较了复发和难治性多发性骨髓瘤患者的无进展生存期（PFS）结果与每周一次和每周两次的卡非佐米给药方案。1  研究设计 第3阶段，开放标签，随机，多中心ARROW试验比较使用每周一次的卡非佐米70 mg / m 2和每周两次地塞米松27 mg / m 2  患有复发和难治性多发性骨髓瘤的患者。所有患者最近的治疗都难以治愈（例如硼替佐米或伊沙唑嗪）并且患有可测量的疾病。患者按1：1随机分入每周一次的组; 卡非佐米被在第1天，8给药，和所有循环的15（20毫克/米2的循环1和70毫克/米的第1天给予2之后），加地塞米松或每周两次基; 卡非佐米在第1,2,8,9,15和16天给药（第1天和第2天20mg / m 2，第1周期和之后27mg / m 2），加地塞米松。1 根据研究开始时的阶段，年龄（<65或≥65）以及患者是否在基线时对硼替佐米难以治疗，对随机化进行分层。1 主要终点是PFS。次要终点包括总体反应率（ORR;部分反应，非常好的部分反应，完整反应和严格的完整反应），总生存期（OS）和安全性。设计了一项事后分析来评估进展时间。1 在基线时，两组的中位年龄为66岁，大多数患者为男性（每周一次，55％;每周两次，54％）。每周一次的组中有更多的患者（46％）对之前的硼替佐米治疗难以治疗，而每周两次组（38％）则难以治疗。1  功效 功效分析中包括478名患者（每周一次组，n = 240;每周两次组，n = 238）。在意向治疗人群中，有274个疾病进展或死亡事件（每周一次，n = 126;每周两次，n = 148）。PFS显着改善，每周一次给药，而每周两次给药（P = .0029）; 中位PFS为11.2个月，每周一次给药，7.6个月，每周两次给药。1 每周一次与每周两次给药相比，进展时间和ORR也显着改善（P = .0015和P）<.0001，分别）。中位数进展为12.4个月，每周一次给药，8.5个月，每周两次给药。在每周一次的组中，ORR为62.9％，对治疗的最佳反应包括完全反应或更好（n = 17）; 非常好的部分反应（n = 65）; 部分反应（n = 69）; 最小响应（n = 14）; 和稳定的疾病（n = 33）。每周一次的患者中有21名患者患有进行性疾病。在每周两次的组中，ORR为40.8％，对治疗的最佳反应包括完全反应或更好（n = 4）; 非常好的部分反应（n = 28）; 部分反应（n = 65）; 最小响应（n = 26）; 和稳定的疾病（n = Read more...