Sequencing Ipilimumab Immunotherapy Before or After Chemotherapy (Nab-Paclitaxel and Bevacizumab) for the Treatment of BRAFwt (BRAF Wild-Type) Metastatic Malignant Melanoma: Results of a Study of Academic and Community Cancer Research United (ACCRU) RU261206I.
化疗 (Nab-紫杉醇和贝伐单抗) 治疗BRAFwt (BRAF野生型) 转移性恶性黑色素瘤之前或之后的测序Ipilimumab免疫治疗: 学术和社区癌症研究联合 (ACCRU) RU261206I的研究结果。
- 作者列表："Markovic SN","Suman VJ","Javed A","Reid JM","Wall DJ","Erickson LA","Ernstoff M","Anderson DM
OBJECTIVES:With the introduction of novel immune therapeutics for the treatment of disseminated malignancies, we sought to evaluate whether deliberate sequencing of immunotherapy before/after conventional cytotoxic chemotherapy would have an impact on clinical outcomes in patients with previously treated metastatic melanoma. We sought to evaluate whether or not ipilimumab immunotherapy administered before or after cytotoxic chemotherapy (nab-paclitaxel+bevacizumab, AB) would impact clinical outcomes. METHODS:We conducted a randomized phase 2 clinical trial of patients with BRAF wild-type metastatic melanoma (up to 2 prior therapies) who received either: (A) AB followed by ipilimumab therapy at progression; or (B) ipilimumab followed by AB treatment at progression. The primary goal of the study was a comparison of AB versus ipilimumab progression-free survival, with secondary clinical and laboratory endpoints. RESULTS:This study did not reach full accrual due to concurrent Food and Drug Administration approval of anti-programmed cell death 1 agents. Nevertheless, the available data suggests a cumulative therapeutic advantage to the sequential use of ipilimumab followed by AB. Correlative laboratory data revealed a favorable effect on systemic immune homeostasis in patients receiving AB therapy, of potential interest in further investigations, especially in the context of chemotherapy/immunotherapy combinations. CONCLUSION:Albeit limited in scope, our data suggest that cytotoxic therapy with nab-paclitaxel and bevacizumab appear to favorably alter systemic parameters of immune function of potential benefit in combination T-cell directed immune checkpoint inhibitor therapy.
目的: 随着治疗播散性恶性肿瘤的新型免疫疗法的引入，我们试图评估传统细胞毒性化疗前/后免疫治疗的刻意测序是否会对既往治疗过的转移性黑色素瘤患者的临床结局产生影响。我们试图评估在细胞毒性化疗 (nab-紫杉醇 + 贝伐单抗，AB) 之前或之后给予ipilimumab免疫治疗是否会影响临床结局。 方法: 我们对接受以下任一治疗的BRAF野生型转移性黑色素瘤患者进行了一项随机 2 期临床试验 :( a) AB后行ipilimumab治疗; 或 (B) ipilimumab后行AB治疗。该研究的主要目标是比较AB与ipilimumab无进展生存期，以及次要临床和实验室终点。 结果: 由于食品和药物管理局同时批准抗程序性细胞死亡 1 剂，本研究未达到完全应计。尽管如此，现有数据表明，序贯使用ipilimumab后使用AB具有累积治疗优势。相关实验室数据显示，在接受AB治疗的患者中，对全身免疫稳态有有利影响，对进一步研究有潜在兴趣，特别是在化疗/免疫治疗组合的背景下。 结论: 尽管范围有限，我们的数据表明，在联合T细胞导向的免疫检查点抑制剂治疗中，nab-紫杉醇和贝伐单抗的细胞毒性治疗似乎有利地改变了潜在获益的免疫功能的全身参数。
METHODS:OBJECTIVE:Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT). METHODS: :Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed. RESULTS: :Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369-1142). All patients completed PT and received a median of 5 HT sessions (range, 2-6). Median follow-up was 18 months (range, 9-26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9-72). All patients experienced acute Grade 2-3 local pain. One patient presented with a late Grade 3 iliac fracture. CONCLUSION:Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial. ADVANCES IN KNOWLEDGE: :This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
METHODS:BACKGROUND:National guidelines recommend screening and treatment for cancer-related bone disease and continued monitoring of bone-modifying agents. It is unclear whether a standardized screening tool is utilized to identify eligible patients and ensure appropriate supportive care is implemented. The purpose of this study was to evaluate current prescribing practices and optimize management of bone-modifying agents. METHODS:A retrospective chart review was performed to identify patients who received hormone deprivation therapy or had bone metastases through Hematology/Oncology or Urology clinics from 1 November 2016 to 31 October 2017. The primary endpoints of this study were the incidence of completed baseline dual-energy X-ray absorptiometry (DEXA) scan for patients on hormone deprivation therapy and percent of patients started on a bone-modifying agent for the prevention of skeletal-related events secondary to bone metastasis. Secondary endpoints included percent of patients with dental examinations prior to initiation, adequate calcium and vitamin D supplementation, incidence of osteonecrosis of the jaw or flu-like symptoms and education, and percent of bisphosphonate doses appropriately adjusted based on renal function. RESULTS:A total of 375 patients were assessed for baseline DEXA scans and bone-modifying therapy. Of the 226 patients on hormone deprivation therapy, 111 (49%) patients were appropriately screened with a DEXA scan prior to initiation of hormone deprivation therapy. Among the 149 patients with bone metastases, only 94 (63.1%) patients were started on a bone-modifying agent. CONCLUSIONS:Opportunities have been identified to optimize management of patients with cancer-related bone disease. Implementation of standardized tools may increase the rate of appropriate screening and initiation of bone-modifying therapy when warranted.
METHODS:PURPOSE:Low skeletal muscle mass has been associated with poor prognosis in patients with advanced lung cancer. However, little is known about the relationship between skeletal muscle mass and overall survival in patients with bone metastases from lung cancer. The objective of the present study was to evaluate the prognostic value of low trunk muscle mass in predicting overall survival in these patients. METHODS:The data from 198 patients who were diagnosed with bone metastases from lung cancer from April 2009 to May 2017 were retrospectively reviewed. The areas of the psoas and paravertebral muscles were measured at the level of the third lumbar vertebra on computed tomography scans taken at the time nearest to the diagnosis of bone metastasis. Muscle area was evaluated for male and female cohorts separately using different cutoff points. Cox proportional hazards analysis was performed to evaluate the factors independently associated with overall survival. RESULTS:The overall survival of patients in the lowest quartile for psoas muscle area or paravertebral muscle area was significantly shorter than that of patients above the 25th percentile for muscle area (p < 0.001). Multivariate analyses showed that paravertebral muscle mass (hazard ratio, 1.73; 95% confidence interval, 1.17-2.56; p = 0.006), epidermal growth factor receptor-targeted therapy, and performance status were independent prognostic factors. CONCLUSIONS:Low paravertebral muscle mass was associated with shorter survival, independently of known prognostic factors.