TNBC vs Non-TNBC: A Retrospective Review of Differences in Mean Age, Family History, Smoking History, and Stage at Diagnosis

Clinical Advances in Hematology & Oncology June 2014, Volume 12, Issue 6 Khurram Tariq, MD, Arezo Farhangi, MD, and Fauzia Rana, MD The authors are affiliated with […]

Update on the Use of Angiogenesis Inhibitors in Adult Patients With Brain Tumors

Clinical Advances in Hematology & Oncology May 2014, Volume 12, Issue 5 David A. Reardon, MD Dr Reardon is the clinical director of the Center for […]

Prescribing for Older Patients With Cancer

Clinical Advances in Hematology & Oncology May 2014, Volume 12, Issue 5 Beatriz Korc-Grodzicki, MD, PhD, Manpreet K. Boparai, PharmD, CGP, and Stuart M. Lichtman, MD […]

Endocrine Therapy for Advanced Breast Cancer

Clinical Advances in Hematology & Oncology April 2014, Volume 12, Issue 4 Payal D. Shah, MD, and Maura N. Dickler, MD Dr Shah is a medical oncology […]

Selective Bcl-2 Inhibition to Treat Chronic Lymphocytic Leukemia and Non-Hodgkin Lymphoma

Clinical Advances in Hematology & Oncology April 2014, Volume 12, Issue 4 Samuel Y. Ng, MD, PhD, and Matthew S. Davids, MD Dr Ng is a clinical […]

The Development of Bevacizumab in Noncolorectal Gastrointestinal Malignancies: Gastroesophageal, Pancreatic, and Hepatocellular Carcinoma

Clinical Advances in Hematology & Oncology April 2014, Volume 12, Issue 4 Manish A. Shah, MD Dr Shah is an associate professor of medicine at Weill Cornell […]

Targeted Therapies for Treatment of Recurrent Ovarian Cancer

Ovarian cancer remains the leading cause of death among women with gynecologic malignancies in the United States. Most women with epithelial ovarian cancer present with advanced disease. Despite good response rates to initial surgery and chemotherapy, the majority of patients experience relapse and ultimately die of their disease. A better understanding of the molecular differences underlying the histologic subtypes of epithelial ovarian cancer has led to recent advances in targeted therapeutic strategies. Here we review the most promising targeted therapeutics currently being used for the treatment of recurrent ovarian cancer.

Treatment Selection in Metastatic Renal Cell Carcinoma: More Confusion or a Path Forward?

Meaningful progress has been realized in the treatment of metastatic renal cell carcinoma with the recent approval of a number of new agents; more new agents are on the horizon. Despite the recent completion of many clinical trials that have changed or will change practice, many questions remain. In this manuscript, we highlight the most noteworthy developments in the first- and second-line treatment of metastatic renal cell carcinoma, as these are the areas of greatest change. We also emphasize ongoing trials and those areas that are most in need of study in order to move the field forward. Although more data are needed, exciting progress is being made.

The Clinical Management of Chronic Myelomonocytic Leukemia

Chronic myelomonocytic leukemia (CMML) is an aggressive malignancy characterized by peripheral monocytosis and ineffective hematopoiesis. It has been historically classified as a subtype of the myelodysplastic syndromes (MDSs) but was recently demonstrated to be a distinct entity with a distinct natural history. Nonetheless, clinical practice guidelines for CMML have been inferred from studies designed for MDSs. It is imperative that clinicians understand which elements of MDS clinical practice are translatable to CMML, including which evidence has been generated from CMML-specific studies and which has not. This allows for an evidence-based approach to the treatment of CMML and identifies knowledge gaps in need of further study in a disease-specific manner. This review discusses the diagnosis, prognosis, and treatment of CMML, with the task of divorcing aspects of MDS practice that have not been demonstrated to be applicable to CMML and merging those that have been shown to be clinically similar.

How Often Do Hematologists Consider Celiac Disease in Iron-Deficiency Anemia? Results of a National Survey

Background: Celiac disease (CD) is underdiagnosed, and iron-deficiency anemia (IDA) is a common presentation of CD. No guidelines exist in the literature for screening for CD among those with IDA in the United States. We surveyed hematologists to determine rates of CD screening in patients with IDA. Methods: A survey was e-mailed to members of the American Society of Hematology. Results: There were 385 complete responses from 4551 e-mails. Most respondents were practicing clinicians (74%), clinical researchers (10%), or laboratory researchers (6%). Specialists in benign hematology accounted for 45% of respondents, oncologists accounted for 33%, and specialists in malignant hematology accounted for 22%. The most common practice types were university-affiliated hospital (43%), private clinic (29%), community hospital (12%), and Veterans Affairs or military hospital (9%). Only 8.6% believed all patients with IDA should be screened for CD. Respondents who had completed their fellowship within 5 years were more likely than more experienced clinicians to believe that all patients with IDA should receive CD screening (OR, 2.8; CI; 1.1-7.5; P=.04). Having a higher volume of IDA patients per month also increased the likelihood of testing (P=.01). In multivariate analysis, specialists in malignant hematology (OR, 3.2; CI, 1.1-9.5; P=.04) and oncologists (OR, 3.5; CI, 1.3-9.5; P=.02) were more likely than specialists in benign hematology to screen all patients for CD, as were those who saw predominately pediatric patients with IDA vs adult patients (OR, 16.9; CI, 3.0-97.0; P=.002). Conclusions: Practicing hematologists infrequently screen for CD in IDA. Physicians who have recently finished their fellowship and those who see a high volume of patients with IDA are more likely to screen for CD.

Programmed Death-1 Inhibition in Renal Cell Carcinoma: Clinical Insights and Future Directions

The treatment of metastatic renal cell carcinoma (mRCC) has evolved markedly over the past decade, broadening beyond immune-based strategies (eg, interleukin-2 and interferon-α) to include targeted agents (eg, sunitinib [Sutent, Pfizer] and sorafenib [Nexavar, Bayer]). Recently, there has been a renewed interest in immune-based strategies, with clinical trials underway to assess vaccines and other immunomodulatory agents. Of particular interest are agents that inhibit the interaction between the programmed death-1 (PD-1) receptor and its ligand (PD-L1) at the T-cell/antigen-presenting cell interface. This interaction produces T-cell anergy and therefore stifles the antitumor immune response. Monoclonal antibodies to PD-1 (eg, nivolumab, lambrolizumab, and pidilizumab) and PD-L1 (MPDL3280A and BMS-936559) are in various stages of clinical development. The clinical trajectory of these agents is discussed herein, with specific attention to the potential placement of PD-1/PD-L1 inhibition in the crowded therapeutic landscape of mRCC.

FDG-PET Imaging for Hodgkin Lymphoma: Current Use and Future Applications

A significant amount of data has been published over the past decade regarding the clinical utility of F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the diagnosis and management of Hodgkin lymphoma (HL). This includes studies examining interim FDG-PET, which has been shown to be a strong tool for predicting relapse and survival, especially in advanced-stage HL. Despite progress, a number of questions remain regarding the precise role and value of FDG-PET in the diagnosis, risk stratification, and management of HL. These questions include the need for concomitant contrast enhanced computed tomography with FDG-PET, reproducibility and interpretability of FDG-PET, optimal imaging for the treatment surveillance of HL following definitive treatment, and the use of FDG-PET for patients with relapsed/refractory disease, including stem cell transplantation. In this review, these issues are critically examined and the study designs and results of observational and prospective FDG-PET response-adaptive clinical trials in HL are described in detail. In addition, novel techniques and future applications of FDG-PET, such as metabolic tumor volume, tumor proliferation via 3’-deoxy-3’-18F-fluorothymidine, and integrated PET/magnetic resonance imaging are discussed.

The Role of Tyrosine Kinase Inhibitors in Hepatocellular Carcinoma

Since the approval of the multityrosine kinase inhibitor (TKI) sorafenib (Nexavar, Bayer and Onyx) as the standard of care for intermediate to advanced stages of hepatocellular carcinoma (HCC), there has been considerable interest in developing more potent TKIs to improve morbidity and mortality for patients with HCC. Much of the research on TKIs targets pathways implicated in angiogenesis, given that HCC is a highly vascularized cancer type. It was theorized that the efficacy of sorafenib is primarily attributable to its angiogenesis targets—namely, vascular endothelial growth factor receptors, platelet-derived growth factor receptors, FLT-3, and RAF kinases. Over the past 2 years, several pivotal phase 3 trials of newer TKIs targeting similar pathways have failed to meet criteria for superiority or noninferiority to sorafenib. Reasons for this may stem from the genetic and biologic heterogeneity of HCC. Genomic studies of tumor samples have shown scarce uniformity in kinase mutations, underscoring the variability that exists in HCC. This beckons the question of whether efforts should shift to other potential targets, either within the realm of TKIs or other targets entirely. Receptor tyrosine kinases, such as those encoded by the MET proto-oncogene, are expressed in certain individuals and have shown to be susceptible to targeted TKIs. As researchers continue to investigate therapies, the goal is to further research efforts into culprit oncogenes that mediate tumor progression, which will likely lead to more personalized and targeted regimens.

Clinical Biomarkers in Colorectal Cancer

Colorectal cancer remains the second leading cause of cancer-related death in the United States. While chemotherapy remains the backbone upon which treatment for metastatic colorectal cancer is built, targeted therapies have been employed, albeit with mixed results, in the management of this disease. Nonetheless, increased understanding in recent years of the complexity and heterogeneity of cellular abnormalities driving these tumors has identified potential targets for future interventions. This article will review the seminal biomarkers of predictive and prognostic importance currently used in the treatment of patients with colorectal cancer, and will highlight additional promising biomarkers which may be incorporated into clinical practice in the future.

The Potential Role for Neoadjuvant Therapy in Renal Cell Carcinoma

Surgical resection remains the standard of care for clinically localized renal cell carcinoma (RCC). Nearly 1 in 4 patients will have a recurrence after surgery performed with curative intent, and stand to benefit from additional therapy. Currently, no proven adjuvant or neoadjuvant therapies are available. A number of phase 3 adjuvant therapy trials are ongoing that are evaluating small-molecule drugs approved for metastatic RCC. The outcomes of these trials may provide insights for designing future phase 3 neoadjuvant therapy trials. Several phase 2 neoadjuvant trials for RCC have recently been completed or are ongoing. These trials have established the safety and response rates associated with several agents, and will pave the way for future phase 3 trial of neoadjuvant therapy for RCC. Neoadjuvant therapies may be useful for decreasing the risk of recurrence after surgery, maximizing nephron sparing, and evaluating molecular effects of targeted therapies in human tumors. Renal cancers make up approximately 4% of all malignancies and account for approximately 2% of cancer-related deaths in the United States.1 In 2013, it is estimated that 65,150 people will be diagnosed with cancers of the kidney or renal pelvis, and approximately 13,680 people will die of their disease. Approximately 34% of patients present with metastatic or regionally advanced kidney cancer.2 Renal cell carcinoma (RCC) is the most common malignancy of the adult kidney. Localized RCC is most often treated with surgery, such as a partial or radical nephrectomy.3 Unfortunately, approximately 23% of patients diagnosed with localized RCC relapse after surgery.4 Better treatment strategies are therefore needed for patients at highest risk for recurrence. Neoadjuvant therapy refers to nonsurgical treatment administered prior to surgery for localized cancer. It is a more specific term than presurgical therapy, which can refer to preoperative treatment for both localized and metastatic disease. Neoadjuvant therapy is distinct from adjuvant therapy, which is administered after curative resection of clinically localized disease. This article will focus on systemic Neoadjuvant therapy, renal cell carcinoma, presurgical therapy, kidney cancer neoadjuvant therapy. At this time, there is no established role for neoadjuvant therapy in RCC. Therefore, we discuss potential opportunities for using neoadjuvant therapies.

Monoclonal B-Cell Lymphocytosis: Update on Diagnosis, Clinical Outcome, and Counseling

Monoclonal B-cell lymphocytosis (MBL) is a clonal B-cell disorder characterized by less than 5 • 109/L B lymphocytes in the peripheral blood, with a characteristic immunophenotype and no lymphadenopathy or organomegaly. The vast majority of MBL cases express the immunophenotype of chronic lymphocytic leukemia (CLL; CLL-like MBL), although non-CLL MBL also exists. CLL-like MBL, which is the focus of this review, is divided into low-count MBL (median B-cell count: 0.001 • 109/L, typically identified in population-based screening studies using highly sensitive flow cytometry assays) and high-count MBL (clinical MBL, median B-cell count: 2.9 • 109/L, typically identified during the workup of low-level lymphocytosis). Low-count MBL has an exceedingly small risk of progression to CLL, and these patients do not require any specific follow-up. In contrast, patients with high-count MBL have a 1% to 2% per year risk of progression to CLL requiring therapy, as well as a higher risk of infectious complications and secondary malignancies. Although the overall survival of high-count MBL patients collectively is similar to the age- and sex-matched general population, 5-year survival for high-count MBL with higher-risk biologic parameters appears to be slightly lower than that of the general population. This review summarizes key concepts in the classification, diagnosis, and biology of CLL-like MBL and addresses several important issues in clinical management.

Clinical Phenotypes of Castration-Resistant Prostate Cancer

Castration-resistant prostate cancer (CRPC) is defined as prostate cancer that no longer responds to androgen deprivation therapy. At the genome level, CRPC is a heterogeneous disease that is marked by a range of genetic and epigenetic lesions. These lesions differ from patient to patient, but have common pathway-based themes. Clinically, a range of phenotypic presentations or subtypes of CRPC are observed that mirror this underlying heterogeneity as the disease progresses; each phenotype carries a different prognosis and different implications for treatment. In this review, we discuss the clinical subtypes of CRPC based on histology; the presence of metastatic disease and pattern of spread; patient-reported symptoms; and levels of biomarkers, such as serum bone turnover biomarkers, prostate-specific antigen, circulating tumor cell enumeration, and neuroendocrine biomarkers. We then address the potential relationship between these clinical phenotypes (with their underlying molecular subtypes) and therapeutic decision making and prognosis, as well as ongoing research strategies.

Treatment Paradigms in Advanced Non–Small-Cell Lung Cancer

Lung cancer is the most common cause of cancer-related death worldwide, owing to its metastatic spread at the time of diagnosis. As a result, chemotherapy is the standard of care for the majority of patients. In recent years, the role of chemotherapy has expanded to include maintenance therapy and approved second- and third-line treatments. Nonetheless, traditional chemotherapy has modestly improved outcomes in patients with advanced non–small-cell lung cancer (NSCLC). Research efforts have been redirected toward the integration of molecularly-targeted agents into a treatment algorithm with unprecedented survival rates in selected patients. This article will provide an update on the multiple systemic regimens available to treat NSCLC, and discuss emerging molecular-based therapies.

A Drug’s Life: The Pathway to Drug Approval

In the United States, drugs and medical devices are regulated by the US Food and Drug Administration (FDA). A drug must undergo rigorous testing prior to marketing to and medical use by the general public. The FDA grants marketing approval for drug products based on a comprehensive review of safety and efficacy data. This review article explains the history behind the establishment of the FDA and examines the historical legislation and approval processes for drugs, specifically in the fields of medical oncology and hematology. The agents imatinib (Gleevec, Novartis) and decitabine (Dacogen, Eisai) are used to illustrate both the current FDA regulatory process—specifically the orphan drug designation and accelerated approval process—and why decitabine failed to gain an indication for acute myeloid leukemia. The purpose and construct of the Oncologic Drugs Advisory Committee are also discussed, along with examples of 2 renal cell cancer drugs—axitinib (Inlyta, Pfizer) and tivozanib—that used progression-free survival as an endpoint. Regulatory approval of oncology drugs is the cornerstone of the development of new treatment agents and modalities, which lead to improvements in the standard of cancer care. The future landscape of drug development and regulatory approval will be influenced by the new breakthrough therapy designation, and choice of drug will be guided by genomic insights.

Risk Stratification in Multiple Myeloma, Part 2: The Significance of Genetic Risk Factors in the Era of Currently Available Therapies

Multiple myeloma (MM) is a heterogeneous disease, and a variety of risk factors at the time of initial diagnosis can be used to stratify patients. In the first part of this 2-part series, we reviewed the currently identified prognostic factors, characterized by disease burden, host factors, tumor biology, and depth of response to therapy. However, these risk factors cannot be interpreted independently of therapies. Novel therapies have the potential to worsen or improve outcomes compared with conventional therapy in high-risk patients, or actually overcome the high-risk status, thereby resulting in reclassification as standard risk. For example, thalidomide (Thalomid, Celgene) is associated with worse outcomes in patients with high-risk cytogenetic abnormalities, such as deletion of chromosomes 13 and 17p, whereas proteasome inhibitors appear to overcome t(4;14). The second part of this series reviews the significance of various genetic risks in the era of novel therapies for MM.