significantly decreased mortality from breast cancer (BC).
Areas covered: Translational research advanced clinical testing of extended adjuvant therapy with tamoxifen or aromatase inhibitors (AIs). Short term therapy or non-compliance increase
recurrence, but surprisingly recurrence and death does not increase dramatically after 5 years of adjuvant therapy stops.
Expert commentary: Compliance ensures optimal benefit from extended antihormone adjuvant therapy.Retarding acquired resistance using CDK4/6 or mTOR inhibitors is discussed. Preventing acquired resistance from mutations of ER could be achieved with Selective ER Downregulators (SERDs), eg fulvestrant. Fulvestrant is a depot injectable so oral SERDs are sought for extended use. In reality, a ‘super SERD’ which destroys ER but improves women’s health like a Selective ER Modulator (SERM), would aid compliance to prevent recurrence and death. Estrogen-induced apoptosis occurs in 30% of BC with antihormone resistance. The ‘one in three’ rule that dictates that one in three unselected patients respond to either hormonal or antihormonal therapy in BC occurs with estrogen or antiestrogen therapy and must be improved. The goal is to maintain patients for their natural lives by blocking cancer cell survival through precision medicine using short cycles of estrogen apoptotic salvage therapy, and further extended antihormone maintenance. 相似文献
Areas covered: This review gives a brief overview of the contemporary clinical data on lenvatinib including its mechanism of action, pharmacokinetics, efficacy and safety profile in combination with everolimus. The clinical applications of lenvatinib in combination with everolimus are addressed within the context of the current competitive therapeutic landscape of RCC.
Expert commentary: Lenvatinib is a new VEGF receptor-targeted tyrosine kinase inhibitor approved in combination with everolimus for second-line therapy in patients with advanced renal cell carcinoma progressing on a first-line VEGF receptor-targeted tyrosine kinase inhibitor. The combination of lenvatinib with everolimus significantly improved progression-free survival compared with everolimus with a hazard ratio of 0.40 and increased objective response to 43%. Optimal sequence of therapy targeting the tumor and the immune system remains a challenge and further investigation is warranted. 相似文献
Areas covered: There are ongoing efforts to augment further the use of targeted agents as adjuvant treatment in BC, hoping that early introduction of targeted therapy blocking key oncogenic drivers of micro-residual disease, will significantly improve clinical outcomes. In the present Review, we present data through extensive search of PubMed about the following targeted adjuvant therapeutic strategies in BC: i) HER2 blockade and ongoing efforts to further augment its efficacy for patients with HER2-positive disease, ii) angiogenesis inhibition, iii) PI3K-mTOR- AKT pathway inhibition, iv) CDK4/6 inhibition, v) PARP inhibition.
Expert commentary: we provide insights about challenges and potential ways to overcome them, in terms of successful clinical development of targeted agents as adjuvant therapy for patients with BC. In particular, we emphasize the need to systematically assess minimal residual cancer burden as a way to increase the rates of successful clinical development of targeted agents in the adjuvant setting. 相似文献
Areas covered: In the METEOR trial, cabozantinib demonstrated significantly improved efficacy in all three endpoints; response rates, progression free survival and overall survival in a randomized trial with everolimus as an active comparator. Cabozantinib also showed activity in the front line setting in RCC within the CABOSUN trial. The study randomized untreated metastatic RCC patients to either cabozantinib or sunitinib and the former showed improved progression free survival which was the primary endpoint. The future holds promise for indications in other malignancies, given the preliminary efficacy and unique mechanism of action of cabozantinib.
In this review we address the mechanism of action, pharmacodynamics and pharmacokinetics of cabozantinib, and also review the development pathway of this agent in the treatment of advanced renal cell carcinoma. The potential benefit in specific patient populations, such as poor risk patients and bone metastases subgroups is also discussed.
Expert commentary: The clinical applications of cabozantinib will be addressed within the context of the current competitive therapeutic landscape of RCC. 相似文献
Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed.
Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy. 相似文献
Areas covered: This article summarizes current strategies for the medical treatment of SI-NETS.
Expert commentary: The treatment plan of advanced-stage SI-NETs should be tailored in a case-by-case manner with the adoption of a multidisciplinary approach that combines different treatment options, including biological targeted therapies. In particular, we believe that the identification of the optimal treatment sequence(s), correct treatment timing and the selection of patients eligible to different treatments need specific investigation in controlled clinical trials. 相似文献
Areas covered: This article reviews epidemiology, pathology and pathogenesis, diagnosis, clinical staging, prognostic factors and treatment modalities of early stage and advanced RCC.
Expert commentary: Although treatment options are expanding rapidly, practicing physicians face considerable challenges in the decision-making process. Therapeutic agents may have unique side effects and unexpected drug interactions. RCC represents one of the major success stories of clinical oncology in recent years and the progress appears to be far from having reached a plateau. We aim to present a comprehensive in-depth review of RCC in an attempt to provide evidence-based recommendations and future perspectives for practicing oncologists. 相似文献
Areas covered: We provide a comprehensive review using PubMed and ClinicalTrials.gov about the following immunotherapies in RCC: i) vaccine therapy, ii) adoptive T Cell Transfer and CAR T cells, iii) nonspecific immunotherapy – IL-2 (new formulations), iv) Checkpoint inhibitors, v) other checkpoint-molecules. We will also discuss their mechanism of action and toxicity, the importance of developing new patient selection algorithms (immunoprofiling, guidelines updates) and new biomarkers such as PD-1 expression.
Expert commentary: Immunotherapy shows promise, and the current tools used in clinical practice, including guidelines, staging-classification and algorithms should be revised and adapted to the new immunotherapeutic drugs. Although immunotherapy in RCC show promising results, more research is needed in parallel to discover biomarkers that enable the prediction of a treatment response and therefore lead to better patient selection. 相似文献
Areas covered: Based on a comprehensive literature search of MEDLINE, EMBASE and conference proceedings of ESMO, ASCO and EAU meetings, this review provides an overview on current and potential future treatment options for platinum-refractory germ cell cancer patients including cytostatics and molecularly targeted therapies.
Expert commentary: Treatment of platinum-refractory disease remains challenging and long-term survival is rarely achieved despite multimodal treatment approaches. Targeted treatment approaches do not yet play a role in the treatment of platinum-refractory disease due to lacking efficacy in small, unselected clinical trials. Inclusion of patients into clinical trials is strongly recommended. 相似文献
Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer.
Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration. 相似文献
Areas Covered: In several clinical trials, BRAF and MEK inhibitors have shown improvement in progression free and overall survival, along with much higher tumor response rates in comparison to chemotherapy, with the combination of these drugs superior to monotherapy. These agents are also being tested in earlier-stage patients, in addition to alternative dosing regimens and in combinations with other therapeutics. Efforts are also ongoing to expand the success found with targeted therapies to other subtypes of melanoma, including NRAS and c-kit mutated melanomas, uveal melanomas, and BRAF/NRAS wild type melanomas.
Expert Commentary: We aim to provide an overview of clinical outcomes with targeted therapies in melanoma patients. 相似文献
Areas covered: This review will critically appraise the evidence base underpinning the main treatment approaches in operable oesophagogastric adenocarcinoma, highlighting variations in treatment by factors such as geographical area and primary tumor site.
Expert commentary: The expert commentary will focus on the optimal evidence-based approaches for clinicians at the present time and explore how increased understanding of the molecular and genetic determinants of the disease may lead to refinements in treatment through the development of both biomarker-driven approaches and the application of novel targeted and immune-modulating agents to early treatment. 相似文献
Areas covered: The purpose of this paper was to review the safety, activity and efficacy of the MEK inhibitor binimetinib for the treatment of NRAS-mutant melanoma, as well as to discuss future therapeutic perspectives such as multiple pathways, targeted therapy, and combinations with immunotherapy.
Expert commentary: Only a modest progression-free survival (PFS) benefit was observed in NRAS-mutated patients who received binimetinib compared with dacarbazine in a randomized phase 3 clinical trial, with no improvement in overall survival. Nevertheless, binimetinib represents another promising treatment option for advanced melanoma and the first molecularly targeted therapy for the NRAS-mutant population. Binimetinib may also have a role in treating NRAS-mutated melanoma patients after failure of immunotherapy. 相似文献
Objective: To determine risk factors for the development of AKI in patients treated for endocarditis.
Methods: This single centre, retrospective univariate and multivariate analysis to determine risk factors for the development of AKI included patients diagnosed with endocarditis between January 2009 and October 2013.
Results: Of 211 included patients, a total of 84 (39.8%) patients developed AKI. We identified multiple independent variables associated with the development of AKI, including: age ≥ 65 years, presence of hardware, chronic kidney disease, AKI on admission, infection with Staphylococcus spp, receipt of nafcillin or oxacillin or aminoglycoside and nafcillin or oxacillin or aminoglycoside and vancomycin, vancomycin trough level ≥ 20.0 mcg/ml, aminoglycoside total daily dose reduction, duration of vancomycin exceeding three days, receipt of loop diuretic or more than three concomitant nephrotoxins and duration of loop diuretic or non-steroidal anti-inflammatory drug therapy exceeding seven days.
Conclusions: In patients treated for endocarditis, multiple risk factors for AKI were identified. Prospective studies are needed to evaluate these variables for causation of AKI in patients treated for endocarditis. 相似文献
Areas covered: In this paper, we present an in depth overview on the state of the art on these key issues of refining decision-making in adjuvant anti-HER2 therapy.
Expert commentary: Despite many important research efforts in the field, chemotherapy plus trastuzumab for a total duration of 1 year remains the standard of care. However, recent data showed that besides standard anthracycline- and taxane-based cytotoxic therapy, alternative chemotherapy regimens can now be proposed to patients with small tumors without nodal involvement and to women at high-risk of developing cardiotoxicity. Of note, besides HER2 itself, biomarkers predicting patients who may truly benefit from anti-HER2 agents are still lacking. 相似文献
Areas covered: The current literature on pancreatic adenocarcinoma treatment modalities has been summarized, with a focus on clinical trials and reviews. New treatment strategies and their impact on clinical practice have also been discussed.
Expert commentary: Despite many therapeutic developments, only modest improvements in survival rates have been achieved. There is an essential need to increase survival by developing more innovative treatment approaches for patients with PC. 相似文献
Areas Covered: This article reviews safety and efficacy data from the phase I, II, and III clinical trials that have led to the approval of nivolumab for the treatment of patients with advanced RCC who have previously been treated with VEGF-directed therapy.
Expert Commentary: Given the overall survival advantage with nivolumab compared to previously approved therapy, nivolumab is a new standard of care in the second-line setting for patients with advanced RCC. Additional studies are underway to answer important questions including the identification of biomarkes and the use of nivolumab in treatment-naïve patients. 相似文献
Areas covered: In this review, the different available neoadjuvant treatments including chemotherapy, bio-chemotherapy, targeted therapy, immunotherapy and local therapy will be presented and discussed. The PubMed published articles were identified and searched using the following terms located in the publication title: neoadjuvant therapy and melanoma. Studies investigating targeted therapy, immunotherapy and local melanoma treatments were included. Clinicaltrial.gov was also used as a source for recruiting or ongoing but not recruiting neoadjuvant clinical trials, for which no published results are available.
Expert commentary: Targeted therapy and immunotherapy in a neoadjuvant setting are still under investigation and not yet approved, however several neoadjuvant trials are ongoing. Shortly, results from these trials will answer the question whether neoadjuvant treatment translates into survival benefit and improves local disease control in stage III and IV melanoma patients. Immunotherapy and targeted therapy will play as relevant a role as in the metastatic setting, whereas chemotherapy will be used seldom. 相似文献
Methods: A web-based survey was emailed to 63 ROs, who were identified through publications, guideline panel membership, and/or affiliation with institutions of high MCC volume. ROs provided treatment recommendations for two hypothetical case scenarios of early stage MCC.
Results: Among 28 respondents (45%), 26 regularly saw and treated MCC patients for a median 7 years (range, 0–30). While all ROs recommended adjuvant radiation for a stage II upper extremity MCC, only 48% recommended adjuvant radiation for stage I head and neck MCC.
Conclusion: Among US-based MCC RO ‘specialists,’ there is equipoise on the role of radiotherapy for stage I MCC. Ideally, prospective studies are needed to identify which patients may benefit from radiation. 相似文献