Journal: Expert review of anticancer therapy
Therapeutic options for clinical Stage I nonseminomatous germ cell tumor include active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND). Lymphovascular invasion (LVI) determines risk of recurrence, as those without LVI have 15% risk of relapse on surveillance while those with LVI have a 50% risk. This stratifies patients into high risk(LVI+) and low risk(LVI-) groups which direct treatment recommendations. Surveillance is preferred for those with low risk disease, and is an option for those with high risk disease, as at least half are over-treated with other options. Adjuvant chemotherapy is an option for all patients as it can eradicate micrometastatic disease and reduce recurrence by at least 90%. RPLND benefits patients with low volume retroperitoneal disease with a cure rate of RPLND alone at approximately 70%. All three treatment modalities have similar survival rates approaching 100% but differing potential morbidities, which, along with patient preferences and compliance, should guide treatment decisions.
Malignant mesothelioma (MM) is an aggressive malignancy of the pleura and other serosal membranes originating from mesothelial cells that, despite decades of research, continues to have limited therapeutic options and is associated with a poor prognosis. Areas covered: MMs induce a strong inflammatory response that is also associated with neoangiogenesis and activation of proangiogenic factors. Given this, several anti-angiogenic agents have been trialled in a variety of malignancies including mesothelioma. Herein we summarise the role of angiogenesis in MM and the current available data targeting these pathways. Expert commentary: The addition of bevacizumab to cisplatin/pemetrexed chemotherapy is currently a therapeutic option with a proven 2.7 month overall survival benefit in fit patients less than 75. Other antiangiogenics such as nintedinib show early promise, although the Phase III trial results are eagerly awaited before this therapy enters treatment paradigms. Beyond this, it is likely that combinations of antiangiogenics with immunotherapies will be investigated in future studies.
While the disease specific mortality of differentiated thyroid cancer has remained low with current treatments, its incidence has been steadily rising over the past several decades, and cancer related recurrence and morbidity have remained a significant problem. Quality indicators currently employed are relevant to the surgical intervention, but do not necessarily reflect oncological outcomes. Therefore, thyroid cancer specific surgical quality indicators, that offer insight into risk of cancer related morbidity and mortality are needed.
Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies. Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC. Expert commentary: While there are compelling data for various therapeutics for the treatment of M0 CRPC, no clear standard of care is apparent at this time. Furthermore, technological advances in imaging may have a significant impact on this future of this disease state.
CD40 is a promising therapeutic target for cancer immunotherapy. In patients with advanced solid malignancies, CD40 agonists have demonstrated some anti-tumor activity and a manageable toxicity profile. A 2(nd) generation of CD40 agonists has now been designed with optimized Fc receptor (FcR) binding based on preclinical evidence suggesting a critical role for FcR engagement in defining the potency of CD40 agonists in vivo. Areas covered: We provide a comprehensive review using PubMed and Google Patent databases on the current clinical status of CD40 agonists, strategies for applying CD40 agonists in cancer therapy, and the preclinical data that supports and is guiding the future development of CD40 agonists. Expert commentary: There is a wealth of preclinical data that provide rationale on several distinct approaches for using CD40 agonists in cancer immunotherapy. This data illustrates the need to strategically combine CD40 agonists with other clinically active treatment regimens in order to realize the full potential of activating CD40 in vivo. Thus, critical to the success of this class of immune-oncology drugs, which have the potential to restore both innate and adaptive immunosurveillance, will be the identification of biomarkers for monitoring and predicting responses as well as informing mechanisms of treatment resistance.
Initial data of immune based therapy showed promise for improving malignant mesothelioma (MM) treatment. However, the results of such treatments have neither been predictable nor consistent and recent clinical studies of immune checkpoint inhibitors in MM have dampened initial enthusiasm.
Hypomethylating agents (HMAs) are the standard of care for patients with higher-risk myelodysplastic syndromes (MDS), but patients who relapse or are refractory have a poor prognosis with an estimated survival of 4-6 months. Rigosertib, a RAS mimetic that inhibits the phophoinositide 3-kinase and polo-like kinase pathways, has been tested in patients with higher-risk MDS following treatment with HMAs, where there are no approved second-line therapies.
Trastuzumab, a humanized anti-HER2 monoclonal antibody targeting the extracellular domain of this oncoprotein, represents the archetype of HER2 blocking agents. Its unprecedented efficacy for HER2-positive metastatic breast cancer (BC) led to its clinical development in the adjuvant setting. The HERceptin Adjuvant (HERA) is one of the pivotal adjuvant trastuzumab trials which proved that this compound can change the natural course of early stage HER2-positive BC. The HERA study led to the registration of trastuzumab for the adjuvant treatment of early HER2-positive BC. This trial randomized more than 5000 patients between 1 and 2 years of trastuzumab and observation after the completion of locoregional therapy and (neo)-adjuvant chemotherapy. Additionally, an abundance of subsequent substudies were conducted, addressing important clinical issues for this patient population. The present review article presents a comprehensive overview of the HERA study and its major contributions to the adjuvant treatment of HER2-positive BC patients. Emphasis is given on the lessons learned from this international collaborative experience and how this can be used as a stepping stone for further improvements in the field.
Metastatic spinal disease is a source of significant morbidity in patients with cancer. Recent advancements in adjuvant oncologic therapy has led to increased survival for many patients who harbor neoplastic disease. As a result of this, the chance of developing metastatic spinal disease over the course of a cancer patient’s lifespan has increased. Symptomatic metastatic spinal disease can cause significant morbidity including severe pain, neurologic deficit, and loss of ambulation. Current treatment of these patients typically involves the use of multiple modalities, including surgery, radiation, and chemotherapy. Areas covered: An extensive literature review was performed to support the author’s opinion on the matter of surgical management of spinal metastatic disease. Pubmed was utilized as a primary search engine. Expert Commentary: Despite advances in chemotherapy and radiation therapy, surgery remains a mainstay in many of these patients, particularly with those with either significant metastatic spinal epidural compression or spinal instability. This review discusses the surgical management of metastatic spinal disease including a framework for decision making and technical considerations when deciding to operate on these patients.
The prognosis of recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (HNSCC) after failure of first line chemotherapy is dismal. Until the publication of the results of CheckMate 141, not a single agent provided any survival benefit as a second line treatment for R/M HNSCC. Areas covered: A comprehensive review of the literature was conducted on the role of nivolumab in HNSCC. Expert commentary: Nivolumab is approved by the Food and Drug Administration for the treatment of patients based on the results of CheckMate 141 showing an overall survival benefit as compared to standard care (single agent docetaxel, methotrexate, or cetuximab). Of particular interest are immune-related adverse events which should be managed according to published guidelines.