黑色素瘤治疗药物的研究进展

黑色素瘤是临床上常见的皮肤恶性肿瘤,且发病率呈逐年增加的趋势。该病恶性程度高,易发生转移。全球新批准并上市的治疗黑色素瘤的治疗药物有威罗菲尼、达拉菲尼、曲美替尼、易普利姆玛、nivolumab以及pembrolizumab,处于研发后期的黑色素瘤治疗药物有cobimetinib、binimetinib、talimogene laherparepvec、贝伐单抗、seviprotimut-L、NGc GM3/VSSP以及c-Kit抑制剂甲磺酸伊马替尼等。对近年来上市和处于研发后期的黑色素瘤的治疗药物进行了详细介绍,同时对其未来发展方向进行了展望,以期为黑色素瘤治疗药物的研发指明方向,给黑色素瘤患者带来希望。     

Real-world Treatment Patterns and Reasons for Therapy Selection in Patients with Advanced Hepatocellular Carcinoma in US Oncology Practices

BackgroundThe treatment landscape for advanced hepatocellular carcinoma (aHCC) is rapidly expanding beyond tyrosine kinase inhibitors (TKIs) in the first-line (1L) setting, with multiple TKIs and immune-checkpoint inhibitors (ICIs) now being evaluated in combination. Real-world evidence describing current treatment patterns and reasons for 1L and 2L treatment selection in aHCC is sparse.Patients and MethodsA retrospective cohort study with a cross-sectional survey element was conducted using Cardinal Health’s Oncology Provider Extended Network. U.S. medical oncologists identified adult aHCC patients initiating 1L systemic therapy between January 1, 2017 and July 31, 2019 and abstracted data from patient medical records. Data included provider characteristics, patient demographics and clinical characteristics, treatment regimens, and physician rationale for treatment regimen choice.ResultsA total of 44 medical oncologists provided data on 284 aHCC patients. The median age at 1L initiation was 61.5 years, and the majority were male (78%) and white (66%). Nearly half (47%) initiated 1L treatment in 2019, 34% were ECOG performance status 2+, and 63% were Child-Pugh Class B/C. Among the 284 aHCC patients, TKIs were used by 94% of patients in the 1L setting, comprised predominantly of sorafenib (54%) and lenvatinib (38%). ICIs were most common among the 90 patients (66%) who received 2L treatment.ConclusionIn the community-oncology practice setting, nearly all aHCC patients received sorafenib or lenvatinib in the 1L setting, while the majority of patients received an ICI in the 2L setting. With recent ICI approvals in aHCC, this marks the beginning of an increased use of ICIs in the 1L setting.     

贝伐珠单抗联合长春瑞滨二线治疗复发转移性宫颈癌患者的近期疗效

目的:观察贝伐珠单抗联合长春瑞滨治疗复发转移性宫颈癌的近期疗效及不良反应。方法:回顾性分析2014年1月至2016年12月贵州省人民医院收治的34例复发转移性宫颈癌患者的临床资料,所有患者均使用贝伐珠单抗联合长春瑞滨,21天为1个周期,行4～6个周期治疗,评价疗效及评定不良反应级别。结果:34例宫颈癌患者中无完全缓解患者,部分缓解7例（20.6%）、疾病稳定20例（58.8%）、疾病进展7例(20.6%）,总有效率为 20.6%（7/34）,疾病控制率为79.4%（27/34）。34例患者常见不良反应程度均较轻,可以耐受。结论:贝伐珠单抗联合长春瑞滨方案治疗复发转移性宫颈癌患者近期疗效好,其不良反应患者可耐受,远期疗效有待进一步的研究。     

Risk factors for an atherothrombotic event in patients with diabetic macular edema treated with intravitreal injections of bevacizumab

AIM: To identify risk factors for an atherothrombotic event (ATE) among patients who were treated for DME with intravitreal bevacizumab injections. METHODS: This retrospective study enrolled all consecutive patients with DME who were treated by intravitreal bevacizumab from 2009 through 2016 in a single center. They were divided into one group treated by bevacizumab and subsequently had an ATE and a second group also treated by bevacizumab and did not have an ATE. RESULTS: A total of 455 patients with DME were enrolled. Seventy-two of the patients had an ATE. A multivariate model adjusted for age, gender, smoking, body mass index, HbA1c, duration of diabetes, creatinine, and blood pressure revealed an increased risk for ATE in the patients with diabetic duration of more than 13y, a systolic blood pressure over 153 mm Hg at first treatment, or having been treated by more than 4 intravitreal bevacizumab injections. Additionally, patients that had an ATE within 3mo from the last intravitreal treatment underwent more bevacizumab injections (5.17±3.82 vs 3.08±1.96; P=0.0003). CONCLUSIONS: The risk factors for an ATE identified in this study were systolic blood pressure >153.5 mm Hg, a history of diabetic mellitus for more than 13y, and treatment with more than 4 intravitreal bevacizumab injections. These factors need to be borne in mind when bevacizumab is being considered in the management of patients with DME.     

Combination of CRAFITY score with Alpha-fetoprotein response predicts a favorable outcome of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma

Immune checkpoint inhibitors (ICIs) with atezolizumab plus bevacizumab are promising agents for unresectable hepatocellular carcinoma (HCC). We tried to guide the treatment based on recent developed CRAFITY score combining with on-treatment AFP response. Eighty-nine patients who received atezolizumab plus bevacizumab regardless of as a first-line therapy or not for unresectable HCC were enrolled for analyses. Radiologic evaluation was based on modified Response Evaluation Criteria in Solid Tumors (mRECIST). The objective response rate (ORR) and disease control rate (DCR) were 25.0% and 65.5%, respectively. Multivariate analysis showed that low CRAFITY score (AFP<100 ng/ml or CRP<10 mg/l) and satisfactory AFP response at 6 weeks (≥75% decrease or ≤10% increase from baseline) were independent factors determining good overall survival (OS) (hazard ratio [HR]=0.143, P=0.002 & HR=0.337, P=0.031), progression-free survival (PFS) (HR=0.419, P=0.022 & HR=0.429, P=0.025) and good responder (odds ratio [OR]=1.763, P=0.044 & OR=3.881, P=0.011). Patients were further divided into three classes by combination of CRAFITY score and AFP response at 6 weeks [The CAR (CRAFITY score and AFP-Response) classification)]: low CRAFITY score with satisfactory AFP response at 6 weeks (class I), either high CRAFITY score or unsatisfactory AFP response at 6 weeks (class II) and high CRAFITY score together with unsatisfactory AFP response at 6 weeks (class III). ORR was 35.0%, 18.2%, and 0% in class I, II and III patients, respectively (overall P=0.034). Patients in the class I had the best OS and PFS, followed by class II and class III (median OS: not reached vs. 11.1 vs. 4.3 months, log-rank P<0.001; median PFS: 7.9 vs. 6.6 vs. 2.6 months, log-rank P=0.001). Combination CRAFITY score and AFP response at 6 weeks with AUROC predicts OS and tumor response to be 0.809 and 0.798, respectively, better than either CRAFITY score (0.771 & 0.750) or AFP response at 6 weeks (0.725 & 0.680) alone. In conclusions, the CAR classification which combining CRAFITY score and AFP response at 6 weeks provides a practical guidance for atezolizumab plus bevacizumab therapy in unresectable HCC patients.