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: 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: 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 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: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors.
Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents. 相似文献
Areas covered: The current review will summarize the clinical evidence of checkpoint inhibitors in bladder cancer, with a focus on pembrolizumab.
Expert commentary: Category 1 evidence indicates that the checkpoint inhibitor pembrolizumab improves overall survival in patients with locally advanced or metastatic urothelial carcinoma who progressed after or during cisplatin-containing therapy as compared to current standard of care chemotherapy. Phase 1 and 2 evidence also indicates that checkpoint inhibitors are active in first line in patients who are ineligible for cisplatin-containing chemotherapy. 相似文献
Areas covered: This article discusses the journey of fulvestrant licensing, its efficacy in combination with other endocrine therapies and the future role it may have within breast cancer treatment.
Expert commentary: Within phase III trials, fulvestrant has demonstrated equivalent or improved clinical efficacy when compared with established endocrine agents. In the recent decade, fulvestrant has achieved licensing as a second line agent in non-operative advanced breast cancer at initially 250mg, increasing to 500mg. Presently, fulvestrant is licensed globally as first line endocrine management for advanced breast cancer in post-menopausal women. Early combination trials of fulvestrant and cyclin dependent kinase 4/6 inhibitors have demonstrated good clinical efficacy with improved progression free survival when compared to fulvestrant alone. 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
Methods: A series of meetings were held throughout Italy, and participants were asked how much they agreed with each of the several statements.
Results: The majority of oncologists agreed that the concept of the minimum biologically effective dose should be used for drugs administered metronomically. Over 50% agreed that metronomic vinorelbine is an option in first-line chemotherapy for patients with advanced breast cancer, including those with a terminal illness and the elderly, as well as in young and fit patients. Just over one-third of experts agreed that a combination of two chemotherapy agents instead of one is not desirable in metastatic breast cancer because of increased toxicity. Most experts agreed that the main aim of a first-line therapy is to control the disease over time and to preserve quality of life.
Conclusion: Metronomically administered oral vinorelbine, either as monotherapy or in combination with other drugs, is effective in the long-term treatment of patients with advanced breast cancer. The clinical profiles of patients should be carefully considered to determine the appropriate treatment strategy. 相似文献
Areas covered: Sonidegib is an oral hedgehog pathway inhibitor with a novel structure. It has recently been licensed for the treatment of laBCC.
This article provides a comprehensive review of the literature regarding sonidegib, detailing the pharmacology of the compound, clinical trial data, competitor compounds and a future perspective.
Expert commentary: Sonidegib is a novel smoothened (SMO) inhibitor with comparable efficacy to vismodegib, with patient response rates of 44% (sonidegib) and 43% (vismodegib). The adverse effect profile of these two treatments is similar with the main effects being considered to be class effects of SMO inhibitors. 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
A systematic review was conducted to evaluate the efficacy and toxicity of adding oxaliplatin to a fluoropyrimidine (intervention) compared with fluoropyrimidine alone (control) in the treatment of LARC.
Methods: We searched CENTRAL, Medline Ovid, PubMed and EMBASE databases. Randomised trials comparing the intervention and control delivered either pre- or post-operatively were included.
Results: Seven trials involving 4444 patients were identified; five studies evaluated the intervention vs control preoperatively; one study peri-operatively; and one, post-operatively. There was no significant difference in OS with oxaliplatin addition, HR 0.89, 95% CI, 0.75 to 1.06. There was however an improvement in disease free survival, 3-year local and distant recurrence rates (RR) favouring oxaliplatin. Preoperative oxaliplatin improved pathological complete response (pCR), but with a greater toxicity and reduced compliance with radiation.
Conclusion: There is no OS benefit with oxaliplatin, despite improved pCR, local and distant RR. Before drawing definitive conclusions, longer follow-up in included trials and availability of published data from other eligible studies, including the induction setting, are needed. 相似文献
Areas Covered: This review outlines critical factors regulating the outcome of DC immunotherapy in ovarian cancer, summarizes the important findings in ovarian cancer DC clinical trials, and discusses new directions which may improve the effectiveness of DC immunotherapy.
Expert Commentary: Administration of DC vaccines with other forms of immunotherapy may enhance the efficacy of these treatments, ultimately increasing cures for this disease. 相似文献
Areas covered: This review describes the EGFR pathway and its abnormalities in NSCLC and discusses the differential molecular and clinical activity of first and next-generation EGFR TKIs in the first-line treatment of tumors with an activating EGFR mutation, with a special focus on the second-generation agent afatinib. A comprehensive literature search was conducted to identify all relevant clinical trials including abstracts from most recent meetings to provide up-to-date information on this topic.
Expert commentary: While the first-generation EGFR TKIs erlotinib and gefitinib exhibited good tolerability and improved progression-free survival compared with a platinum doublet, they failed to improve overall survival (OS). In contrast, clinical trials of afatinib (LUX-Lung 3 and 6) demonstrated a significant OS advantage over a platinum doublet, particularly in patients whose tumors harbored the Del19 mutation. Moreover, in a head-to-head comparison afatinib improved efficacy versus gefitinib in patients with common EGFR mutations across a range of clinically relevant endpoints. Afatinib is therefore a promising first-line option in these 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 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: In this article, we focus on the development of durvalumab and provide an overview of the safety, activity, efficacy and future perspectives of this drug in urothelial carcinoma.
Expert commentary: Durvalumab is a well-tolerated drug and demonstrated major and durable response in advanced bladder cancer. Combinations with durvalumab will probably emerge as promising therapeutic strategies for the treatment of urothelial carcinoma. Further research efforts are needed to identify predictive biomarkers of response to immune-oncology agents. 相似文献
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: The published literature on EBRT for advanced pT4 disease and macroscopic unresectable disease to improve locoregional control is reviewed. EBRT techniques, volumes and doses are discussed in detail. The potential acute and late toxicities of EBRT are discussed in the context of the published literature. The use of EBRT for patients with metastatic disease is also described.
Expert commentary: There is good retrospective evidence for EBRT in the setting of unresectable gross residual well-differentiated thyroid cancer as this can result in long-term local control. However, the benefit of EBRT in patients with locally advanced disease that is completely resected is less clear. The use of EBRT for these patients requires careful consideration of age, pathologic factors, comorbidities and patient preference, preferably by a multi-disciplinary team. 相似文献
Areas covered: This review will focus on the current results and the future development of the therapeutic approaches for the treatment of SCLC.
Expert commentary: Immunotherapy is becoming a new frontier for the management of SCLC with preliminary interesting results. To date, no targeted drugs have been approved for clinical practice but several novel agents are in an advanced stage of clinical development in SCLC. 相似文献