Mechanism of Pathway: Phosphatidylserine, an Immune-Modulating Checkpoint, Ushers in the Next Wave of Immuno-Oncology Targets

  • Phosphatidylserine (PS) is an immune checkpoint distinct from PD-1/PD-L1, CTLA-4, and other antagonists or agonists of T-cell activation
  • Tumors compromise the body’s normal immunosuppressive process of clearance/disposal of dying cells through PS-signaling mechanisms to evade immune detection
  • PS exposure in the tumor microenvironment is immunosuppressive and increases in response to chemotherapy and radiation therapy
  • Bavituximab is an investigational monoclonal antibody that targets PS and is believed to override PS-mediated immunosuppressive signaling in tumors prevalent in the tumor microenvironment, as well as to provide an immune-activating signal through Fc-γ receptor signaling

Phosphatidylserine, an Immune-Modulating Checkpoint, Ushers in the Next Wave of Immuno-Oncology Targets

The immune system recognizes and is poised to eliminate cancer but is held in check by a plethora of inhibitory pathways that regulate cellular immune responses.1 These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during antimicrobial immune responses, can be co-opted by cancer to evade [ Read More ]

The Socioeconomic Burden of Patients with Chronic Pain

Managed care organizations (MCOs) must play a pivotal role in the management of patients with chronic pain. Payers already recognize that pain is one of the most prevalent chronic conditions and that it is generally associated with significant comorbidities. As noted in the main article in this publication, there may [ Read More ]

Gary M. Owens, MD

Reducing the Negative Effects of Opioids While Adequately Managing Pain

Practitioners, healthcare providers, governing bodies, and patients all agree that there are significant gaps in the adequate management of pain in our current healthcare system. In addition, there are great concerns among practitioners regarding the social effects of ramping up opioid use for the management of chronic pain. These concerns [ Read More ]

Paul M. Hamrah, MS, PharmD

Addressing the Socioeconomic Burden of Chronic Pain

The main article in this publication highlights the rising incidence of chronic pain that afflicts 43% of the adult US population (as of 2010).1 In addition, the author discusses the disparities that exist in terms of pain assessment and treatment for several disadvantaged groups, including the elderly, women, ethnic/racial minorities, [ Read More ]

Jennifer M. Hah, MD, MS

Socioeconomic Burden of Chronic Pain

Chronic pain is a debilitating condition that is associated with significant medical, emotional, and economic burdens. The International Association for the Study of Pain defined chronic pain as pain that persists past the normal time of healing, which may be less than 1 month, or more commonly, 3 months.1 However, [ Read More ]

Sabby Muneer, PhD

Immunotherapy Will Alter the NSCLC Treatment Landscape

Despite the promise of molecular profiling, approximately 80% of patients with lung cancer lack a defined genotypic mutation and thus become resistant when treated with a tyrosine kinase inhibitor. According to data presented at the congress, however, lung cancer remains a highly mutated disease, suggesting great potential for immunotherapy. “If [ Read More ]

Looking into the Future of Lung Cancer Research

Each year, the Bonnie J. Addario Lung Cancer Foundation (ALCF) recognizes luminaries in the quest to cure lung cancer with the Addario Lectureship Award. This year, Fred R. Hirsch, MD, PhD, Professor of Medicine and Pathology, University of Colorado School of Medicine, Denver, delivered his keynote lecture on the many [ Read More ]

Exploring the Possibilities of Manipulating the Immune System to Improve Outcomes

Dear Colleague, We are pleased to continue our in-depth coverage of the role of immunotherapy in oncology care. Immunotherapy has long captured the interest of researchers combating disease, and none more so than oncology researchers. Recent advances in immunotherapy have made headlines and been the main attraction at association meetings. [ Read More ]

Sanjiv S. Agarwala, MD

High-Dose Interleukin-2 as a Second-Line Option in Metastatic Melanoma

An Interview with Elizabeth I. Buchbinder, MD, of Dana-Farber Cancer Institute Many patients with melanoma have benefited from the recent employment of therapeutic agents targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) such as ipilimumab and the immune checkpoint blockade (ICB) agents targeting the programmed death-1/ligand 1 (PD-1/PD-L1) pathway. As more patients are [ Read More ]

Targeting Programmed Death-1 (PD-1) and Its Ligand (PD-L1)

Immunologic checkpoint blockade with antibodies targeting PD-1 or one of its ligands, PD-L1, is showing promise as a method for reversing cancer immunosuppression and thereby promoting immune responses against several cancer types.1 While the first checkpoint inhibitor approved by the FDA in 2011 was ipilimumab, an antibody that targets cytotoxic [ Read More ]

Update to Approaches to Therapy in Malignant Melanoma

Current approaches to the treatment and follow-up of patients with malignant melanoma, including those with brain metastases, were reviewed by speakers at the 2015 World Cutaneous Malignancies Congress. Approach to the BRAF-Positive Patient Melanoma is an immunogenic oncogene-driven cancer, said Grant McArthur, MB, BS, PhD, in explaining the rationale for [ Read More ]

Genetic Testing for Melanoma: What’s State of the Art?

Genetic testing in metastatic melanoma should include testing for all actionable mutations in exon 15, said Grant McArthur, MB, BS, PhD, at the 2015 World Cutaneous Malignancies Congress. Testing at the time of disease progression is not yet ready for routine clinical use. Test the Metastases In metastatic melanoma, tumor [ Read More ]

Another Immunotherapy for NSCLC?

Immunotherapy is poised to become a game changer for patients with non–small cell lung cancer (NSCLC). Nivolumab is now approved by the FDA for the treatment of NSCLC, and atezolizumab is the second checkpoint inhibitor to show promise as second- line or later therapy in NSCLC. Results of the POPLAR [ Read More ]

Two New Options for Renal Cell Carcinoma

Patients with advanced, pretreated renal cell carcinoma (RCC), who have limited treatment options, received good news from 2 important practice-changing trials presented as late-breakers at the recent 2015 European Cancer Congress (ECC)—CheckMate 025 and METEOR. CheckMate 025 found a survival benefit for nivolu­mab over standard everolimus therapy in previously treated [ Read More ]

Intralesional Oncolytic Immunotherapies Show Benefit in Melanoma

For patients with advanced melanoma, checkpoint inhibitors are not the only means of modulating the immune system to treat disease. According to research presented at the American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, intralesional oncolytic therapy is also providing profound benefit in several phase 2 and phase [ Read More ]

The Next Generation of Agents for Lung Cancer

At the 16th Annual International Lung Cancer Congress, Tony Mok, MD, Professor of Clinical Oncology, The Chinese University of Hong Kong, provided an overview of the next generation of agents, taking stock of the recent past for insights into the future of drug discovery. Drug discovery is rarely, if ever, [ Read More ]

Advocacy, Collaboration, and Education: Solutions to Public Health Issues in Chronic Pain

Chronic pain affects approximately 100 million US adults, and has devastating consequences on quality of life (QoL) and functional status.1 Unfortunately, despite the availability of various pharmacologic and nonpharmacologic therapies, many patients with chronic noncancer pain continue to experience moderate or severe symptoms.1 Numerous barriers exist to the optimal management [ Read More ]

Sabeeha Muneer, PhD

Finding Solutions to Public Health Issues in Chronic Pain

The main article in this publication discusses the need for global education and advocacy efforts to improve the care of patients with chronic pain. The Institute of Medicine report on relieving pain stresses the importance of expanding education efforts to multiple stakeholders, including patients, the general public, and healthcare providers, [ Read More ]

Jennifer M. Hah, MD, MS

Addressing Public Health Issues in the Management of Chronic Pain

In the main article in this publication, the author points out various shortcomings of chronic pain management in the United States. In this commentary, I would like to address some of the reasons for such shortcomings as they pertain to the use of opioids for the management of chronic noncancer [ Read More ]

Paul M. Hamrah, MS, PharmD

Meeting the Challenges of Public Health Issues in Chronic Pain

Chronic pain is an issue of major importance for US payers. Although the management of chronic pain is complex and requires multiple medical interventions and therapies, one of the mainstays of treatment is the appropriate use of opioid therapy.1 In this regard, payers are tasked to maintain a balance that [ Read More ]

Gary M. Owens, MD

Personalized Medicine in Oncology: Disseminating Essential Information

Dear Colleague,On behalf of all of us at Personalized Medicine in Oncology (PMO), I’d like to offer our warmest wishes to you this holiday season and our thanks for your loyal readership throughout 2015. Over this past year, we have witnessed advances in our knowledge of tumor biology, biomarkers, and [ Read More ]

The Current Landscape in Melanoma Treatment

An Interview with Jeffrey Infante, MD, of Sarah Cannon Research InstituteThe COMBI-d and COMBI-v trials showed that treating BRAF V600 mutation–positive metastatic melanoma with the combination of da­brafenib plus trametinib resulted in a significant increase in overall survival and a 33% reduction in the risk of progression or death compared [ Read More ]

Commentary: Treatment for Children Receiving Emetogenic Chemotherapy

Chemotherapy-induced nausea and vomiting is a frequent and potentially treatment-limiting complication of cancer therapy in both adults and children. However, pediatric oncologists have been keenly aware that while effective regimens have been developed for adults, effective regimens for children receiving emetogenic chemotherapy have been lacking.1-3 On September 2, 2015, the [ Read More ]

Inherited Colorectal Cancer: POLE and POLD1

The association of POLE and POLD1 with colorectal cancer risk was demonstrated in 2013. Palles and colleagues studied families with a dominant pattern of inherited colorectal cancer and multiple adenomas through whole genome sequencing.1 Through these efforts, they identified germline mutations in POLE and POLD1 as high-penetrance genes predisposing to [ Read More ]

Cristi Radford, MS, CGC; Tuya Pal, MD, FACMG

FDA Approves Opdivo to Treat Advanced Form of Kidney Cancer

On November 23, 2015, the FDA approved Opdivo (nivolumab) to treat patients with advanced (metastatic) renal cell carcinoma, a form of kidney cancer, who have received a certain type of prior therapy. “Opdivo provides an important therapy option for patients with renal cell carcinoma,” said Richard Pazdur, MD, Director of [ Read More ]

FDA Approves Portrazza to Treat Advanced Squamous Non–Small Cell Lung Cancer

On November 24, 2015, the FDA approved Portrazza (necitumumab) in combination with 2 forms of chemotherapy to treat patients with advanced (metastatic) squamous non–small cell lung cancer (NSCLC) who have not previously received medication specifically for treating their advanced lung cancer. Lung cancer is the leading cause of cancer death [ Read More ]

FDA Drug Approvals: Earlier Availability for Promising Drugs

It’s no secret that developing cancer drugs is a time-consuming and costly endeavor. Although the FDA review represents only a fraction of the entire time line, accelerated evaluation can still shave years off this process. According to data presented at the 2015 Breast Cancer Symposium, expedited programs allow for intensive [ Read More ]

The Affordable Care Act: Extending Coverage to Millions of Americans

A closer look at the $2.7 trillion spent on healthcare in the United States in 2011 reveals a system of extreme imbalances, characterized by excessive consumption of care on the one hand and lack of access to necessary care on the other. The Affordable Care Act (ACA), outlined by Otis [ Read More ]

Poliovirus Shows Complete Response in Several Glioblastoma Patients

In a role reversal, poliovirus is fast becoming a viable therapy for one of cancer’s deadliest diseases. Researchers at The Preston Robert Tisch Brain Tumor Center at Duke University Medical Center are using engineered poliovirus to treat recurrent glioblastoma—making tumors disappear and extending survival beyond 3 years in some patients. [ Read More ]

Encouraging New Options for Neuroendocrine Tumors

Patients with advanced neuroendocrine tumors (NETs) have 2 promising new treatment options, according to separate phase 3 studies presented as late-breakers at the 2015 European Cancer Congress. The NETTER-1 trial evaluated the radiopharmaceutical agent 177Lu-DOTATATE in NETs confined to the midgut, while RADIANT-4 evaluated the mTOR inhibitor everolimus in patients [ Read More ]

Oncotype DX Breast Cancer Assay Spares Low-Risk Patients from Chemotherapy

Patients with early breast cancer and a low Oncotype DX Recurrence Score (RS) can be safely treated with hormone therapy alone and avoid chemotherapy, according to results from the National Cancer Institute–sponsored TAILORx trial.1,2 Patients who had an RS of <11 treated with hormone therapy alone had less than a [ Read More ]

Case: PIK3CA-Mutant Triple-Negative Breast Cancer Inhibited by Cetuximab

A woman with PIK3CA-mutant triple-negative breast cancer (TNBC), who is an exceptional responder to cetuximab, illustrates how PIK3CA mutations can induce tumor growth by activating the epidermal growth factor receptor (EGFR), and how these cancers may be successfully inhibited by EGFR inhibitors. Joyce O’Shaughnessy, MD, Chair in Breast Cancer Research, [ Read More ]

The Annual Report of the Personalized Medicine Coalition

(PMO) is a proud partner of the Personalized Medicine Coalition (PMC). PMO and PMC share the common goal of promoting the understanding and adoption of personalized medicine concepts to ultimately benefit patients and the health system. PMC provides opinion leadership on policy issues that affect personalized medicine; helps to educate [ Read More ]

Edward Abrahams, PhD; William S. Dalton, PhD, MD

Sample Size Calculation for Single-Arm Phase 2 Prostate Cancer Trials

Prostate cancer remains one of the major health issues for men worldwide and is the second leading cause of cancer-related death in males in the United States…

Can Metastatic Cancer with Diagnostic Ambiguity Be Treated Based on Mutational Status Alone?

The application of molecularly targeted cancer therapies has rapidly expanded in the past 2 decades. The identification of genetic mutations in tumors has led to a growing list of therapies developed to specifically target those alterations. Indeed, molecularly targeted therapies—along with predictive biomarker testing and site-specific chemotherapy—have significantly improved the [ Read More ]

Wayne Kuznar

In Vitro and Clinical Assessments of Abuse-Deterrent Formulations for Chronic Pain

Chronic noncancer pain is now considered a global epidemic and a public health problem in the United States, partly owing to its prevalence, underdiagnosis, and undertreatment.1 The resultant and unprecedented increase in the use of opioids has become a national concern because of parallel increases in the misuse, abuse, and [ Read More ]

Sabeeha Muneer, PhD

Clinical Assessment of Abuse-Deterrent Formulations

In 1985 and 1996, the World Health Organization issued guidelines on cancer pain relief.1 The ethical mandate for pain treatment has been extended to chronic nonmalignant pain, and some have argued that this type of pain produces suffering similar to that of cancer pain but with a higher prevalence and [ Read More ]

Ofer M. Wellisch, MD, MPH

The Tip of the Iceberg

For as long as prescription opioids have been available for the treatment of patients with chronic, noncancer pain, misuse, abuse, and diversion of these agents have been ongoing issues. The abuse of prescription opioids may lead to high rates of morbidity and mortality, and may be associated with significant increases [ Read More ]

Atheer Kaddis, PharmD

In Vitro and Clinical Assessments of Abuse-Deterrent Formulations in the Management of Chronic Pain

Opioid abuse and diversion are important issues for all payers, as they must balance access to opioids for those who truly need treatment with the potential that these drugs may not be used as intended. This issue is supported by the fact that in 2010, there were 16,651 opioid-related deaths [ Read More ]

Gary M. Owens, MD

Epidemiologic Assessments of Abuse-Deterrent Formulations

Prescription opioid abuse is a significant public health concern in the United States, particularly abuse of controlled-release formulations that contain higher opioid content.1 The enormous abuse potential of prescription opioids is now well-recognized, and strategies to mitigate these risks are being implemented.1,2 This article provides an overview of the government’s [ Read More ]

Sabeeha Muneer, PhD

Abuse-Deterrent Formulations: An Early Epidemiologic Appraisal

A prescription opioid addiction and abuse epidemic has been escalating in the United States over the past 2 decades, having progressively developed into a pressing national public health concern.1 The Institute of Medicine, which was enlisted by the US Department of Health & Human Services to examine pain as a [ Read More ]

Ofer M. Wellisch, MD, MPH

Are We Winning the War on Drugs?

Since the early 1970s, the United States has declared a war on drugs, focusing on ways in which to reduce the use and abuse of illicit and addicting drugs. In addition to law enforcement strategies, the pharmaceutical industry has played a role in trying to curb misuse and abuse of [ Read More ]

Atheer Kaddis, PharmD

Assessing Abuse-Deterrent Formulations: Much Work Still Remains

The human toll from opioid-related abuse and misuse in the United States is a serious public health problem that must be addressed on all fronts. According to the American Society for Addiction Medicine, 46 Americans die each day from prescription opioid overdoses, which translates to 2 deaths per hour and [ Read More ]

Gary M. Owens, MD

Magnifying Mechanisms of Action: an Exclusive Series to PMO

Dear Colleague,Welcome to the inaugural edition of our annual Mechanism of Action Magnifier™! The Magnifier series is an exclusive supplement brought to you by the publishers of Personalized Medicine in Oncology (PMO) to delve into the biochemical interaction through which an oncology drug produces its pharmacological effect. Throughout the year, [ Read More ]

Dabrafenib plus Trametinib: Two Kinase Inhibitors Used in Combination to Target Different Parts of the MAPK Pathway

The MAPK pathway is constitutively activated in the majority of melanomas as a result of molecular alterations in genes encoding key components of the pathway (eg, BRAF and NRAS mutations) or upstream cell surface receptors (eg, KIT), resulting in uncontrolled tumor proliferation and survival (Figure 1).1 Among patients with metastatic [ Read More ]

Blinatumomab: a Bispecific CD19-Directed CD3 T-Cell Engager

Blinatumomab (derived from “B-lineage–specific antitumor mouse monoclonal antibody”) is a bispecific CD19-directed CD3 T-cell engaging antibody that binds to1-3:CD19 (expressed on the surface of cells of B-lineage origin)CD3 (expressed on the surface of T cells).More than 90% of cases of B-cell precursor acute lymphoblastic leukemia (ALL) express CD19 in more [ Read More ]

Duvelisib (IPI-145): a Dual Inhibitor of Phosphoinositide 3-Kinase (PI3K)-Delta and -Gamma

In B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma, the malignant B cells rely on a number of internal and external stimuli to survive, such as the activation of the B-cell receptor, cytokine and chemokine signaling, or direct cell-to-cell interactions. Attracted by chemo­kines, including CXCL12 and [ Read More ]

Ibrutinib: an Inhibitor of Bruton’s Tyrosine Kinase

B cells circulate between multiple sites in the body during their normal life cycle, and these B cells rely on cues from the support of microenvironments to promote proper development, maturation, and function.1 Chemotaxis to, and adhesion within, proliferative microenvironments, as well as intracellular prosurvival signaling that promotes growth and [ Read More ]

Idelalisib: a Selective Inhibitor of the Delta Isoform of Phosphatidylinositol 3-Kinase

There are 4 isoforms of phosphatidylinositol 3-kinase (PI3K) with distinct functions and expression patterns; among those 4 isoforms, PI3K-alpha and PI3K-beta are ubiquitously expressed and involved in a range of cellular functions.1 Both PI3K-gamma and PI3K-delta are expressed predominantly in normal and malignant hematopoietic cells within the bone marrow.1 PI3K-Delta [ Read More ]

Panobinostat: a Histone Deacetylase Inhibitor

In the cell nucleus, DNA is maintained in a tightly coiled state around proteins called histones.1 During the process of DNA replication for cell division or during the synthesis of RNA and proteins, histone ace­tyltransferase adds acetyl groups onto the histones, enabling DNA to uncoil.1 By contrast, histone deacetylases (HDACs) [ Read More ]

Ruxolitinib: a Kinase Inhibitor That Inhibits Overactive JAK Pathway Signaling

Overactive JAK pathway signaling is a key mechanism of disease in the myeloproliferative neoplasms (MPNs) polycythemia vera and myelofibrosis.1,2 Signaling of the JAK pathway plays a key role in normal cell functioning.3-6 Well-regulated JAK signaling is essential for cell production, cell proliferation, and immune function. Intracellular regulators, such as suppressor [ Read More ]

Venetoclax (ABT-199): a Selective Inhibitor of B-Cell Lymphoma-2

Proteins in the B-cell lymphoma-2 (BCL-2) family are key regulators of apoptosis, and the BCL-2 gene is frequently overexpressed in leukemias and lymphomas.1,2 The BH3-only proteins of the BCL-2 family (ie, those having only the BCL-2 homology domain BH3) can trigger apoptosis by binding to the prosurvival members of this [ Read More ]

Abemaciclib (LY2835219): a Dual Inhibitor of CDK4 and CDK6

Cyclin-dependent kinases (CDKs) 4 and 6 are overactive in many human cancers, resulting in a loss of regulation of the G1 cell cycle restriction point and making malignant cells less responsive to normal growth controls.1,2 CDK4 and CDK6 CDKs are key regulators of cell proliferation.3 In many tumor types, CDK4 [ Read More ]

Lenvatinib: a Receptor Tyrosine Kinase Inhibitor

Lenvatinib (Figure) is an orally administered multiple receptor tyrosine kinase (RTK) inhibitor with a novel binding mode that selectively inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors1:VEGFR1 (FLT1)VEGFR2 (KDR)VEGFR3 (FLT4).Lenvatinib also inhibits other RTKs involved in tumor proliferation, including1:Fibroblast growth factor receptors 1, 2, 3, and 4The [ Read More ]

Alectinib: an Anaplastic Lymphoma Kinase (ALK) Inhibitor

ALK Rearrangements in Lung AdenocarcinomaALK has been found to fuse with other partners, leading to potent malignant transformation.1,2 The most common among ALK fusion genes in lung cancer, specifically non–small cell lung cancer (NSCLC), is the EML4 ALK translocation fusion gene (EML4-ALK).1,3-5 The relative prevalence of ALK translocation mutations among [ Read More ]

Bavituximab: a Novel, Investigational Immunotherapy Agent Targeting Phosphatidylserine in the Vasculature of the Tumor Microenvironment

Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that blocks PS-mediated immunosuppression by multifocal reprogramming of immune cells in the tumor microenvironment to support immune activation.1 PS is a highly immunosuppressive molecule usually located inside the membrane of healthy cells, but “flips” and becomes exposed on the outside of cells [ Read More ]

Necitumumab: an Epidermal Growth Factor Receptor Antibody

Overexpression of the epidermal growth factor receptor (EGFR) is correlated with poor prognosis in many human cancers.1 EGFR is a member of the ErbB family of receptor tyrosine kinases (TKs). EGFR activation occurs in response to ligand stimulation and/or genetic alterations of the EGFR gene, such as somatic mutations, amplifications, [ Read More ]

Trabectedin: a DNA-Binding Agent That Covalently Interacts with the Minor Groove of the DNA Double Helix

Trabectedin (ET-743) is a marine alkaloid isolated from the Caribbean tunicate Ecteinascidia turbinata, with a chemical structure characterized by 3 fused tetrahydroisoquinoline rings.1 Trabectedin binds to the minor groove of DNA and alkylates guanine at the N2 position, bending the helix toward the major groove.2,3 In this manner, it is [ Read More ]

Utilizing Pharmacogenomics When Selecting Personalized Medicine for Patients with Chronic Pain

Pharmacotherapy, which remains the cornerstone of chronic pain management, includes analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs), the more potent opioids, and adjunct therapies such as antidepressants and anticonvulsants.1 It is well-recognized that interindividual differences exist in the general population in terms of pain perception, response to analgesic treatment, and [ Read More ]

Sabeeha Muneer, PhD

Personalized Medicine for Patients with Chronic Pain

The new millennium has brought about the promise of genomics for the understanding of disease and the advancement of therapeutic approaches.1 The scientific community has continued to establish the genetic basis of phenotypic variability among individuals and ethnic groups in terms of susceptibility to disease as well as response to [ Read More ]

Ofer M. Wellisch, MD, MPH

Why Is My Patient Still in Pain?

As pharmacists and caregivers, we have all experienced situations in which patients and loved ones continue to experience pain after being treated with proven, advanced analgesics. It leads us to question whether the correct dose was administered, whether the appropriate diagnosis was made, and even whether some other physiologic or [ Read More ]

Atheer Kaddis, PharmD

The Potential for Improved Prescribing: A Payer Perspective

As I have discussed in previous perspectives, the human and economic toll of opioid abuse and misuse is unacceptably high. A multifaceted approach to this serious public health problem is essential and should involve all stakeholders. One emerging area of focus for the effective management of chronic pain is the [ Read More ]

Gary M. Owens, MD

A New Year for Immunotherapy

Dear Colleague, I hope you had great holidays and a happy New Year! In this first issue of the year, we feature an in-depth review about immune checkpoint inhibition in patients with colorectal cancer. This is a continuation of our series on immunotherapy in specific disease states. In this article, [ Read More ]

Sanjiv S. Agarwala, MD

Checkpoint Inhibition: A Promising Immunotherapeutic Approach for Colorectal Cancer

According to the American Cancer Society, colorectal cancer is the third most common cancer in men and women, and the second leading cause of cancer deaths in the United States.1 An estimated 132,700 new cases of, and 49,700 deaths from, colorectal cancer are expected to occur in 2015. For patients [ Read More ]

Pembrolizumab Combination Shows Robust Antitumor Activity

In 3 phase 1 and 2 studies, improved overall response rates (ORRs) were shown in patients with metastatic melanoma taking pembrolizumab (Keytruda) in combination with 3 other immunotherapies, including epa­cadostat, talimogene laherparepvec (Imlygic), and ipi­limumab (Yervoy). All 3 studies demonstrated significant antitumor activity. In addition, long-term follow-up data in a [ Read More ]

Christine Anderson

Certain Types of T-Cells Show Clinical Benefit in Patients with Glioblastoma And other news from the 2015 Society for Immunotherapy of Cancer

Although the current standards of care cannot cure glioblastoma (GBM), an adoptive T-cell transfer may help improve outcomes in patients with GBM. At the 2015 Society for Immunotherapy of Cancer 30th Anniversary Annual Meeting, researchers reported their findings from a phase 1 clinical trial, NCT01109095. They observed patients with progressive [ Read More ]

Christine Erickson

The Coming Government Takeover of Drug Pricing ObamaCare provides the tools for a unilateral move against the industry the left loves to demonize.

Hillary Clinton has plenty of allies as she demonizes drug-company profits and pushes for federal control over how drugs are priced. There’s a drug-pricing task force led by the White House and a similar Democrat-led effort in Congress. Many of the pharma industry’s proponents in Washington and on Wall Street [ Read More ]

Scott Gottlieb, MD

Using Natural Killer Cells in Immunotherapy: What Is Known, and Where to Next

In their review article, Carin I. M. Dahlberg, PhD, from the Cell Therapies Institute, Nova Southeastern University, Fort Lauderdale, FL, and the Cell and Gene Therapy Group, Center for Hematology and Regenerative Medicine, Karolinska University Hospital Huddinge, NOVUM, Stockholm, Sweden, and colleagues evaluated natural killer (NK)-cell–based therapies targeting cancer. In [ Read More ]

E. K. Charles, Medical Writer

On the Cutting Edge of Personalizing Care:
From Molecular Tumor Boards to Cancer Stem Cell Research

Dear Colleague, It is with great enthusiasm that we present this, our first issue of 2016, to you. You will find that we are adapting our presentations to meet the learning needs of our reading community. Specifically, we are expanding our case study presentations to reflect trends in academia as [ Read More ]

Al B. Benson III, MD, FACP, FASCO

Cancer Stem Cell Research: A New Frontier in the Fight Against Cancer:

An Interview with Stanton L. Gerson, MD, Case Comprehensive Cancer Center, and Zev A. Wainberg, MD, University of California, Los Angeles

Dr. Gerson is Director of the Case Comprehensive Cancer Center and the Shiverick Professor of Hematological Oncology and Founding Director of the Ohio Wright Center for Stem Cell and Regenerative Medicine, now called the National Center for Regenerative Medicine.Dr. Wainberg is Assistant Professor of Medicine at the University of California, [ Read More ]


BRAF Mutation in Colorectal Cancer

Anita Turk, MD; Dustin Deming, MD
Division of Hematology and Oncology,Department of Medicine
University of Wisconsin-Madison School of Medicine and Public Health
and University of Wisconsin Carbone Cancer Center, Madison, WI

Advances in molecular pathology have allowed for the widespread use of sequencing technologies to improve our ability to better understand the biology of each individual patient’s cancer. This allows for the personalization of treatment strategies depending on the molecular profile of the cancer. In colorectal cancer (CRC), mutations in KRAS [ Read More ]


Human Epidermal Growth Factor Receptor Type 2 Therapy in Gastrointestinal Tumors

Federico Longo, MD; Alfredo Carrato, MD, PhD
Medical Oncology Department, Ramon y Cajal University Hospital
Madrid, Spain

Case ReportA 64-year-old woman was examined at our emergency department after a 6-month period of suffering from progressive fatigue, anorexia, significant weight loss, and abdominal pain. She had a medical history of active smoking and mixed anxiety-depressive disorder treated with bromazepam and escitalopram. The patient had a performance status of [ Read More ]


Case: Clinically Node-Negative Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare and aggressive cancer with a case fatality rate of 33%. Delayed diagnoses of MCC are common, which results in patients often presenting at advanced stages, said Manisha Thakuria, MD, at the 2015 World Cutaneous Malignancies Congress. The optimal care of MCC is debated. [ Read More ]

Inherited Prostate Cancer

Prostate cancer is the most common nondermatologic cancer in males in the United States. Incidence and mortality rates vary significantly between countries. In the United States, the lifetime risk of developing prostate cancer is approximately 1 in 7, with an incidence similar to that of breast cancer. In 2015, it [ Read More ]

Cristi Radford, MS, CGC

Another Study Shows Benefit with a Pediatric Regimen in Young Adults with ALL

A pediatric regimen achieves superior outcomes compared with adult regimens in adolescents and young adults with acute lymphoblastic leukemia (ALL). Several studies have already shown this outcome, and a multicenter phase 2 study presented at the meeting adds further confirmatory evidence in support of this approach. The multicenter phase 2 [ Read More ]

Daniel DeAngelo, MD, PhD

Venetoclax: Strong Showing in CLL

Venetoclax, an oral, investigational, small molecule Bcl-2 inhibitor, achieved excellent and durable responses in patients with relapsed/refractory chronic lymphocytic leukemia (RR CLL). All patients in the trial harbored a 17p deletion, signaling poor prognosis.In a pivotal phase 2 trial reported at the meeting, nearly 80% of patients with high-risk RR [ Read More ]

Stephan Stilgenbauer, MD

CAR T-Cell Therapy Highly Active in Various Hematologic Malignancies

CAR T cells demonstrated consistent activity in advanced hematologic malignancies evaluated in multiple small clinical trials reported at the meeting.Disease remission persisting for as long as 36 months occurred in 8 of the first 20 patients treated at the National Cancer Institute. The 40% overall response rate included 4 of [ Read More ]

James Kochenderfer, MD

Checkpoint Inhibitors in Lymphoma: A New Universe

Immunotherapy is generating great excitement in melanoma and non–small cell lung cancer (NSCLC). FDA approvals of checkpoint inhibitors in these tumor types, as well as encouraging preliminary results in other solid tumors, have paved the way for studying them in hematologic cancers.Philippe Armand, MD, Dana-Farber Cancer Institute, Boston, MA, discussed [ Read More ]

Philippe Armand, MD

Idelalisib Combined with Bendamustine/Rituximab Boosts Survival in CLL

Idelalisib combined with bendamustine/rituximab (BR) reduced the risk of disease progression and death versus BR alone in patients with relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), according to results from a randomized, double-blind, placebo-controlled, phase 3 late-breaking trial presented at the meeting.Lead investigator Andrew Zelenetz, MD, Memorial Sloan Kettering Cancer Center, [ Read More ]

Andrew Zelenetz, MD

Ibrutinib a New Standard of Care for Elderly CLL Patients

Ibrutinib significantly reduced the risk of disease progression and death compared with standard treatment with chlorambucil in older treatment-naive patients with chronic lymphocytic leukemia (CLL). Ibrutinib achieved a 91% reduction in risk of disease progression and an 84% reduction in the risk of death compared with chlorambucil. These results from [ Read More ]

In Newly Diagnosed Myeloma Patients, Triplets Preferred

While the cost of treating newly diagnosed patients is greatly increased with the use of 3 drugs, doublets should not be considered adequate, and triplets should be the standard of care, according to results from a randomized trial.The use of triplets—including a proteasome inhibitor, immunomodulatory drug (IMiD), and steroid—has been [ Read More ]

Brian G.M. Durie, MD

Midostaurin: First Targeted Therapy in AML Is Potentially Practice Changing

Midostaurin is the first FLT3 inhibitor to improve overall survival in FLT3-mutated acute myeloid leukemia (AML). Midostaurin plus standard chemotherapy improved survival compared with placebo plus chemotherapy as up-front treatment for high-risk patients with AML and FLT3 mutations. Patients and physicians have waited for new drugs for AML since the [ Read More ]

Nilotinib Yields Better Rates of Molecular Response Than Imatinib in the Frontline Setting

Dose-optimized nilotinib increased the rates of major molecular response (MMR) in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) in the ENESTxtnd study. According to final results from this study, the cumulative MMR rate was 78.8% by 12 months and 81.0% by 24 months in patients managed [ Read More ]

Rituximab Boosts Chemotherapy Benefit in B-Cell Precursor ALL

In patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the addition of rituximab to chemotherapy significantly improved event-free survival in a large European study. “Adding rituximab to standard therapy should become a standard of care for these patients,” according to Sébastien Maury, MD, Hôpital Henri Mondor, Créteil, France. The study [ Read More ]

Pembrolizumab Shows Promise in Multiple Myeloma

Monoclonal antibodies targeting programmed death-1 (PD-1) may be effective in multiple myeloma, according to early data on pembrolizumab presented at ASH.In heavily pretreated relapsed/refractory patients, pembrolizumab was combined with lenalidomide/dexamethasone (Rd) in a phase 1 study with 50 patients, where a response rate of 76% was observed (Abstract 505). Pembrolizumab [ Read More ]

Jesus San Miguel, MD

Promising Combo in Elderly Patients with ALL

Elderly patients with acute lymphoblastic leukemia (ALL) are difficult to treat. A new study suggests that frontline treatment with the combination of the investigational antibody-drug conjugate inotuzu­mab ozogamicin plus deintensified chemotherapy is a good option for older patients with this disease. In a phase 2 trial, the combination had impressive [ Read More ]

ESR1 Mutations Portend Worse Survival in ER+ Advanced Breast Cancer

A “liquid biopsy” was able to detect 2 mutations in the estrogen receptor 1 (ESR1) gene that predicted worse overall survival (OS) in women with estrogen receptor–positive (ER+), metastatic breast cancer who were originally enrolled in the BOLERO-2 clinical trial.The presence of a D358G and/or Y537S mutation in the ESR1 [ Read More ]

Sarat Chandarlapaty, MD, PhD

Early Results with Immunotherapy in Breast Cancer

Immunotherapy is a hot topic in cancer right now, with approved checkpoint inhibitors for melanoma and non–small cell lung cancer. Checkpoint inhibitors are also making inroads in other solid tumors.Separate preliminary studies of checkpoint inhibitors in the treatment of breast cancer had less impressive results, but these are early studies, [ Read More ]

Hope S. Rugo, MD

Omit Chemotherapy for Premenopausal Luminal A Breast Cancer?

Younger patients with luminal A subtype breast cancer may not need chemotherapy, according to a Danish trial presented at the 2015 San Antonio Breast Cancer Symposium. Luminal A biological subtype breast cancer has an excellent prognosis, even in high-risk patients, the study suggests.“A large body of evidence suggests that luminal [ Read More ]

Torsten O. Nielsen, MD, PhD

Liquid Biopsy Characterizing CTCs Can Aid in Treatment Selection

A “liquid biopsy” using phlebotomy blood samples can identify phenotypes and genomic characteristics of circulating tumor cells (CTCs) that may help personalize treatment selection for men with advanced prostate cancer.“Hormonal agents prolong the lives of men with castrate-resistant prostate cancer. The optimal sequence of agents to maximize survival is unknown. [ Read More ]

Howard Scher, MD

The Coming Government Takeover of Drug Pricing ObamaCare provides the tools for a unilateral move against the industry the left loves to demonize

Hillary Clinton has plenty of allies as she demonizes drug-company profits and pushes for federal control over how drugs are priced. There’s a drug-pricing task force led by the White House and a similar Democrat-led effort in Congress. Many of the pharma industry’s proponents in Washington and on Wall Street [ Read More ]

Scott Gottlieb, MD

Personalized Medicine at FDA: 2015 Progress Report

One year after the initial observation by the Personalized Medicine Coalition (PMC) of an increased rate of personalized medicine approvals at the FDA Center for Drug Evaluation and Research (CDER), the most recent data show that the trend has continued, with oncology leading the way for the field.A new analysis [ Read More ]

Daryl Pritchard, PhD

Regulation and Reimbursement Policies Will Determine the PMI’s Legacy

On February 25, the Obama administration laid out the next steps for the Precision Medicine Initiative (PMI) before an eager crowd of stakeholders at the White House. The initiative is promising.Zeroing in on President Obama’s vision of building a research cohort that includes 1 million Americans, the National Institutes of [ Read More ]

Edward Abrahams, PhD
President
Personalized Medicine Coalition

First-in-Human CAR T-Cell Trial Shows Activity in Multiple Myeloma

CAR T-cell therapy has been striking in various hematologic malignancies, and, for the first time, the approach is being evaluated in multiple myeloma.At the meeting, James Kochenderfer, MD, of the Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, presented preliminary results from a phase [ Read More ]

James Kochenderfer, MD

Benefit for T-DM1 Confirmed

The antibody-drug conjugate trastuzumab emtansine (T-DM1) improved overall survival (OS) compared with physician’s choice of therapy for patients with pretreated HER2-positive metastatic breast cancer, according to final results from the phase 3 TH3RESA trial. The study was supported by Roche.Treatment with T-DM1 led to a clinically meaningful and statistically significant [ Read More ]

Tamoxifen or Anastrozole for DCIS? Age and Symptom Profiles Matter

Tamoxifen and anastrozole are similarly effective in preventing breast cancer recurrence in postmenopausal women with ductal carcinoma in situ (DCIS). The choice depends on patient preferences, side effect profiles, age, and other patient factors, according to separate studies presented at the 2015 San Antonio Breast Cancer Symposium.In the large, placebo-controlled [ Read More ]

Jack Cuzick, PhD

Adjuvant Chemoradiotherapy May Provide Benefit in Locally Advanced Bladder Cancer

In the United States, the standard of care for locally advanced bladder cancer after radical cystectomy is to “consider” adjuvant chemotherapy and adjuvant radiation. In a 3-arm randomized trial, adjuvant radiation therapy alone or combined with chemotherapy (ie, chemoradiotherapy) did not significantly improve disease-free survival (DFS) compared with adjuvant chemotherapy [ Read More ]

Regular Aspirin Use Reduces the Risk for Prostate Cancer Death

The regular use of aspirin reduces the incidence of and risk for death from lethal prostate cancer according to the results from a large observational study reported at the Genitourinary Cancers Symposium. For the purposes of this study, lethal prostate cancer was defined as metastatic disease or prostate cancer–specific death.Aspirin [ Read More ]

Cabozantinib Improves Standard of Care for Second-Line Treatment of Advanced Kidney Cancer

Cabozantinib achieved superior progression-free survival (PFS) versus standard treatment with everolimus in patients with previously treated advanced kidney cancer in an updated analysis of the phase 3 METEOR trial reported at the Genitourinary Cancers Symposium. In addition, a strong trend toward overall survival (OS) favored cabozantinib at an interim analysis, [ Read More ]

Bernard Escudier, MD

Reirradiation of Pelvic Area Is Safe and Improves Quality of Life

Experience at a high-volume center suggests that reirradiation of the pelvis for cancer recurrence or second genitourinary (GU) malignancy is safe in patients with advanced cancer and can achieve excellent and durable palliation of symptoms without causing severe radiation-induced morbidity. These patients are typically near the end of life, and [ Read More ]