National trends in prescription drug expenditures and projections for 2024.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2024 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2024 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, endocrine drugs, generics, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2024 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2023, overall pharmaceutical expenditures in the US grew 13.6% compared to 2022, for a total of $722.5 billion. Utilization (a 6.5% increase), new drugs (a 4.2% increase) and price (a 2.9% increase) drove this increase. Semaglutide was the top drug in 2023, followed by adalimumab and apixaban. Drug expenditures were $37.1 billion (a 1.1% decrease) and $135.7 billion (a 15.0% increase) in nonfederal hospitals and clinics, respectively. In clinics, increased utilization drove growth, with a small impact from price and new products. In nonfederal hospitals, a drop in utilization led the decrease in expenditures, with price and new drugs modestly contributing to growth in spending. Several new drugs that will influence spending are expected to be approved in 2024. Specialty, endocrine, and cancer drugs will continue to drive expenditures. CONCLUSION: For 2024, we expect overall prescription drug spending to rise by 10.0% to 12.0%, whereas in clinics and hospitals we anticipate an 11.0% to 13.0% increase and a 0% to 2.0% increase, respectively, compared to 2023. These national estimates of future pharmaceutical expenditure growth may not be representative of any health system because of the myriad of local factors that influence actual spending.

National trends in prescription drug expenditures and projections for 2023.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2023 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2023 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, diabetes medications, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2023 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2022, overall pharmaceutical expenditures in the US grew 9.4% compared to 2021, for a total of $633.5 billion. Utilization (a 5.9% increase), price (a 1.7% increase) and new drugs (a 1.8% increase) drove this increase. Adalimumab was the top-selling drug in 2022, followed by semaglutide and apixaban. Drug expenditures were $37.2 billion (a 5.9% decrease) and $116.9 billion (a 10.4% increase) in nonfederal hospitals and clinics, respectively. In clinics, new products and increased utilization growth drove growth, with a small impact from price changes. In nonfederal hospitals, a drop in utilization led to a decrease in expenditures, with price changes and new drugs contributing to growth in spending. Several new drugs that will influence spending have been or are expected to be approved in 2023. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2023, we expect overall prescription drug spending to rise by 6.0% to 8.0%, whereas in clinics and hospitals we anticipate increases of 8.0% to 10.0% and 1.0% to 3.0%, respectively, compared to 2022. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

The Current Landscape for METex14 Skipping Mutations in Non-Small Cell Lung Cancer.

Capmatinib and tepotinib received US Food and Drug Administration (FDA) approval for mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping alteration in 2020 and 2021, respectively. Capmatinib was FDA approved in May 2020 under accelerated approval for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a mutation that leads to METex14 skipping. Accelerated approval was based on overall response rate and response duration to capmatinib, and it was granted orphan drug and breakthrough therapy designation. Capmatinib is a potent selective kinase inhibitor of the MET receptor, crosses the blood-brain barrier, and has shown low-grade adverse events. Based on phase II data, capmatinib demonstrated an overall response rate (ORR) of 41% and a median duration of response (DOR) of 9.7 months in those who previously received one or two lines of therapy. In treatment-naive patients, capmatinib demonstrated a 68% ORR with a median DOR of 12.6 months. The FDA also granted accelerated approval to tepotinib for adult patients with metastatic NSCLC harboring METex14 skipping alteration. Accelerated approval for tepotinib was based on an ORR of 43% with a median DOR of 10.8 months in treatment-naive patients. Among previously treated patients, the ORR was 43% with a median DOR of 11.1 months. Continued approval for capmatinib and tepotinib is contingent upon confirmatory trials. Both agents are now considered first-line therapy or a subsequent therapy option in patients with metastatic NSCLC who are positive for METex14 skipping alterations.

National trends in prescription drug expenditures and projections for 2022.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2022 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2022 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, COVID-19 pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2022 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2021, overall pharmaceutical expenditures in the US grew 7.7% compared to 2020, for a total of $576.9 billion. Utilization (a 4.8% increase), price (a 1.9% increase) and new drugs (a 1.1% increase) drove this increase. Adalimumab was the top drug in terms of overall expenditures in 2021, followed by apixaban and dulaglutide. Drug expenditures were $39.6 billion (a 8.4% increase) and $105.0 billion (a 7.7% increase) in nonfederal hospitals and in clinics, respectively. In clinics and hospitals, new products and increased utilization growth drove growth, with decreasing prices for both sectors acting as an expense restraint. Several new drugs that are likely to influence spending are expected to be approved in 2022. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2022, we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 7.0% to 9.0% and 3.0% to 5.0%, respectively, compared to 2021. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Severe Psychiatric Symptoms in a Patient With EGFR Exon-20 Insertion Mutation Receiving Mobocertinib: A Case Report.

Tyrosine kinase inhibitor therapy is an established standard of care for patients with NSCLC with EGFR mutations, but a worse prognosis has been observed in patients with specific EGFR exon-20 insertion mutations. Mobocertinib (TAK-788) is a novel tyrosine kinase inhibitor developed to target EGFR exon-20 insertion and has exhibited promising response rates and acceptable safety in phase 1 and 2 trials. We report a case of a 59-year-old woman with metastatic NSCLC and EGFR exon-20 mutation responsive to mobocertinib therapy, who developed severe depression and catatonia approximately 4 months after mobocertinib initiation, ultimately necessitating its permanent discontinuation. Given the observed severe depression in this case report, we recommend that, for patients on mobocertinib who develop neuropsychiatric adverse effects, strong consideration should be given for dose interruption or discontinuation.

National trends in prescription drug expenditures and projections for 2021.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2021 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2021 were reviewed-including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for biosimilars, cancer drugs, generics, coronavirus disease 2019 (COVID-19) pandemic influence, and specialty drugs. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2021 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2020, overall pharmaceutical expenditures in the United States grew 4.9% compared to 2019, for a total of $535.3 billion. Utilization (a 2.9% increase) and new drugs (a 1.8% increase) drove this increase, with price changes having minimal influence (a 0.3% increase). Adalimumab was the top drug in 2020, followed by apixaban and insulin glargine. Drug expenditures were $35.3 billion (a 4.6% decrease) and $98.4 billion (an 8.1% increase) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals the decrease in expenditures was driven by reduced utilization. Several new drugs that will influence spending are expected to be approved in 2021. Specialty and cancer drugs will continue to drive expenditures along with the evolution of the COVID-19 pandemic. CONCLUSION: For 2021, we expect overall prescription drug spending to rise by 4% to 6%, whereas in clinics and hospitals we anticipate increases of 7% to 9% and 3% to 5%, respectively, compared to 2020. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

National trends in prescription drug expenditures and projections for 2020.

PURPOSE: To report historical patterns of pharmaceutical expenditures, to identify factors that may influence future spending, and to predict growth in drug spending in 2020 in the United States, with a focus on the nonfederal hospital and clinic sectors. METHODS: Historical patterns were assessed by examining data on drug purchases from manufacturers using the IQVIA National Sales Perspectives database. Factors that may influence drug spending in hospitals and clinics in 2020 were reviewed, including new drug approvals, patent expirations, and potential new policies or legislation. Focused analyses were conducted for specialty drugs, biosimilars, and diabetes medications. For nonfederal hospitals, clinics, and overall (all sectors), estimates of growth of pharmaceutical expenditures in 2020 were based on a combination of quantitative analyses and expert opinion. RESULTS: In 2019, overall US pharmaceutical expenditures grew 5.4% compared to 2018, for a total of $507.9 billion. This increase was driven to similar degrees by prices, utilization, and new drugs. Adalimumab was the top drug in US expenditures in 2019, followed by apixaban and insulin glargine. Drug expenditures were $36.9 billion (a 1.5% increase from 2018) and $90.3 billion (an 11.8% increase from 2018) in nonfederal hospitals and clinics, respectively. In clinics, growth was driven by new products and increased utilization, whereas in hospitals growth was driven by new products and price increases. Several new drugs that will likely influence spending are expected to be approved in 2020. Specialty and cancer drugs will continue to drive expenditures. CONCLUSION: For 2020 we expect overall prescription drug spending to rise by 4.0% to 6.0%, whereas in clinics and hospitals we anticipate increases of 9.0% to 11.0% and 2.0% to 4.0%, respectively, compared to 2019. These national estimates of future pharmaceutical expenditure growth may not be representative of any particular health system because of the myriad of local factors that influence actual spending.

Integrating trastuzumab biosimilars and HER2-directed therapies into HER2-positive breast cancer management.

The approval of the humanized monoclonal antibody trastuzumab in 1998 changed the trajectory of treatment and subsequent outcomes for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and is now the standard of care in the neoadjuvant, adjuvant, and metastatic settings. However, as with most biologic drugs, trastuzumab comes with a relatively high price tag compared with traditional cytotoxic chemotherapy and contributes to healthcare budgets. Three engineered products related to trastuzumab-2 antibody-drug conjugates, ado-trastuzumab emtansine and fam-trastuzumab deruxtecan-nxki, as well as the subcutaneous trastuzumab/hyaluronidase-have since been approved and have expanded the treatment options for this patient population. The approval of 5 trastuzumab biosimilars as of the end of 2019 holds the promise of considerable cost savings, but challenges to integrating their use into patient care must be addressed. Barriers to their use, including physician uncertainty to switch patients from the reference drug to the therapeutic biosimilar and patients' lack of understanding about biosimilars, are common in the United States. It is also important that all stakeholders, including managed care professionals, pharmacists, and practice administrators, understand how to incorporate trastuzumab biosimilars into formulary discussions, clinical care plans and processes, and educational initiatives for healthcare providers and patients.

Pharmacist perspectives and considerations for implementation of therapeutic oncology biosimilars in practice.

PURPOSE: An overview of therapeutic oncology biosimilars, the U.S. biosimilars regulatory pathway, and the clinical development of selected biosimilar products is provided, including discussion of considerations in adopting biosimilars into oncology practice. SUMMARY: Biosimilars are biologic agents that are highly similar to and have no clinically meaningful differences from an approved reference product in terms of safety, purity, and potency. There is a large market for cancer biologics, and approval of biosimilars has the potential to increase access to care and reduce costs. An abbreviated regulatory pathway for the development and approval of biosimilars defines a stepwise approach to demonstrating biosimilarity and conducting clinical comparative trials to confirm equivalent pharmacokinetics, efficacy, safety, and immunogenicity to the reference product. Three therapeutic biologics (bevacizumab, trastuzumab, and rituximab) have been used extensively in the treatment of a variety of cancers and are targets for biosimilar product development. Preclinical and clinical experience with 2 recently approved biosimilars to bevacizumab and trastuzumab is reviewed. Challenges faced by pharmacy and therapeutics committees when considering oncology biosimilars for formulary inclusion are discussed. CONCLUSION: Increased adoption of biosimilars could potentially lower treatment costs and improve access to biologics for patients with cancer. Key considerations in formulary review of biosimilars include the quality and quantity of data from comparative clinical trials, economic factors, manufacturer reliability, and challenges associated with incorporating biosimilars into practice.

Patient-centered design in developing a mobile application for oral anticancer medications.

OBJECTIVES: To develop and test the usability and feasibility of a customizable mobile application (app) designed to help educate patients about their oral anticancer medications (OAMs) and regimens. SETTING: Outpatient cancer center and oncology pharmacy for urban, Midwestern academic health system. PRACTICE DESCRIPTION: Clinically-supervised educational intervention to support patients learning about OAMs. PRACTICE INNOVATION: With input from patient partners, our interdisciplinary team designed the first known tablet-based educational app that can interface with a patient's electronic medical record. The app is based on learning style and adherence theories and is customizable for individually prescribed OAMs. The app can accommodate multiple learning styles through text at 6th-grade reading level, pictures, animations, and audio voiceovers. Functionalities include interactive educational modules on 11 OAMs and case-based patient stories on common barriers to OAM adherence. EVALUATION: Early phase testing provided the opportunity to observe the user interface with the app and app functionality. Data were summarized descriptively from observations and comments of patient subjects. RESULTS: Thirty patient subjects provided input-19 in phase 1 usability testing and 11 in phase 2 feasibility testing. Comments provided by patient subjects during usability testing were largely positive. Responses included self-identification with patient stories, usefulness of drug information, preferences for text messages, and app limitations (e.g., perceived generational digital divide in technology use and potential patient inability to receive text messages). Using their feedback, modifications were made to the prototype app. Responses in feasibility testing demonstrated the app's usefulness across a wide range of ages. Highest opinion ratings on app usefulness were stated by patients who were newer to OAM therapy. CONCLUSION: User feedback suggests the potential benefit of the app as a tool to help patients with cancer, particularly after the first months for those starting new OAM regimens. Processes and lessons learned are transferable to other settings.

Adherence to Oral Anticancer Medications: Evolving Interprofessional Roles and Pharmacist Workforce Considerations.

Interprofessional care is exhibited in outpatient oncology practices where practitioners from a myriad of specialties (e.g., oncology, nursing, pharmacy, health informatics and others) work collectively with patients to enhance therapeutic outcomes and minimize adverse effects. Historically, most ambulatory-based anticancer medication therapies have been administrated in infusion clinics or physician offices. Oral anticancer medications (OAMs) have become increasingly prevalent and preferred by patients for use in residential or other non-clinic settings. Self-administration of OAMs represents a significant shift in the management of cancer care and role responsibilities for patients and clinicians. While patients have a greater sense of empowerment and convenience when taking OAMs, adherence is a greater challenge than with intravenous therapies. This paper proposes use of a qualitative systems evaluation, based on theoretical frameworks for interdisciplinary team collaboration and systems science, to examine the social interactionism involved with the use of intravenous anticancer treatments and OAMs (as treatment technologies) by describing patient, organizational, and social systems considerations in communication, care, control, and context (i.e., Kaplan's 4Cs). This conceptualization can help the healthcare system prepare for substantial workforce changes in cancer management, including increased utilization of oncology pharmacists.

Role of HIV in the desire of procreation and motherhood in women living with HIV in Spain: a qualitative approach.

BACKGROUND: Improved antiretroviral treatments and decrease in vertical transmission of HIV have led to a higher number of women living with HIV to consider childbearing. However, stigma and social rejection result in specific challenges that HIV positive women with procreation intentions have to face with. Our objective was to in depth analyse elements shaping their desire for procreation and specifically investigate the impact of HIV. METHODS: A qualitative study was conducted through open interviews with 20 women living with HIV between 18 and 45 years of age, from the Spanish AIDS Research Network Cohort (CoRIS). Interviews were audio-recorded and transcribed. A content analysis was performed. RESULTS: HIV diagnosis is a turning point in women's sexual and emotional life that is experienced traumatically. HIV diagnosis is usually associated with the fear of an immediate death and the idea of social isolation. At this moment, women temporarily reject future motherhood or having a sexual life. HIV status is only disclosed to the closed social circle and partner support is essential in HIV diagnosis assimilation process. Health professionals provide information on assisted reproductive technology and on how to minimize risk of partner HIV transmission. Most of barriers for procreation acknowledged by women are not related to HIV. However, women fear vertical transmission and experience other barriers derived from HIV infection. In this context, pregnancy makes women feel themselves as "normal women" despite HIV. Motherhood is considered an element of compensation that helps them to cope with HIV diagnosis. All these elements make health professionals key actors: they provide information and support after HIV diagnosis. CONCLUSIONS: Barriers and drivers for procreation are similar among HIV positive women and general population. However, stigma and discrimination linked with HIV weigh in HIV positive women decision of motherhood. In this context, it is necessary to provide these women with the necessary counselling, guidance and resources to take decisions about procreation properly informed.

Pharmacological management of anticancer agent extravasation: A single institutional guideline.

Although the risk of extravasation of a chemotherapy (anticancer) medication is low, the complications associated with these events can have a significant impact on morbidity and health care costs. Institutions that administer anticancer agents should ideally have a current guideline on the proper management of the inadvertent administration of these toxic medications into tissues surrounding blood vessels. It is imperative that the health care team involved in administering drugs used to treat cancer be educated on the risk factors, preventative strategies and treatment of anticancer extravasations, as well as practice safe and proper administration techniques. Anticancer agents are generally divided into classes based on their ability to cause tissue damage. The review of current published guidelines and available literature reveals a lack of consensus on how these medications should be classified. In addition, many recently approved drugs for the treatment of cancer may lack data to support their classification and management of extravasation events. The treatment of the majority of extravasations of anticancer agents involves nonpharmacological measures, potentially in the ambulatory care setting. Antidotes are available for the extravasation of a minority of vesicant agents in order to mitigate tissue damage. Due to the limited data and lack of consensus in published guidelines, a working group was established to put forth an institutional guideline on the management of anticancer extravasations.

BCR-ABL1 tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia.

The management of chronic myeloid leukemia with BCR-ABL1 tyrosine kinase inhibitors has evolved chronic myeloid leukemia into a chronic, manageable disease. A patient-centered approach is important for the appropriate management of chronic myeloid leukemia and optimization of long-term treatment outcomes. The pharmacist plays a key role in treatment selection, monitoring drug-drug interactions, identification and management of adverse events, and educating patients on adherence. The combination of tyrosine kinase inhibitors with unique safety profiles and individual patients with unique medical histories can make managing treatment difficult. This review will provide up-to-date information regarding tyrosine kinase inhibitor-based treatment of patients with chronic myeloid leukemia. Management strategies for adverse events and considerations for drug-drug interactions will not only vary among patients but also across tyrosine kinase inhibitors. Drug-drug interactions can be mild to severe. In instances where co-administration of concomitant medications cannot be avoided, it is critical to understand how drug levels are impacted and how subsequent dose modifications ensure therapeutic drug levels are maintained. An important component of patient-centered management of chronic myeloid leukemia also includes educating patients on the significance of early and regular monitoring of therapeutic milestones, emphasizing the importance of adhering to treatment in achieving these targets, and appropriately modifying treatment if these clinical goals are not being met. Overall, staying apprised of current research, utilizing the close pharmacist-patient relationship, and having regular interactions with patients, will help achieve successful long-term treatment of chronic myeloid leukemia in the age of BCR-ABL1 tyrosine kinase inhibitors.

Design of Customized Mobile Application for Patient Adherence to Oral Anticancer Medications Utilizing User-Centered Design.

Adherence and compliance to oral anticancer medications (OAMs) can be challenging for patients due to their complex regimens. The goal of this research project was to design an effective and engaging user interface (UI), based on user-centered design (UCD) and incorporate animations, to reinforce and improve patient's understanding of the key aspects of taking OAMs. This current paper encompasses the development process and describes the initial phase of the project, which focused on the design and development of the tablet-based educational application (app). A UCD approach was implemented by consulting with oncology clinicians and patients at an early stage of development. Animations were developed and incorporated to convey complex medical concepts and information. An iterative design process will help ensure that the tool is customized for patient engagement.

Targeting the mammalian target of rapamycin pathway with everolimus: implications for the management of metastatic breast cancer.

The inhibitors of mammalian target of rapamycin (mTOR) have documented antitumor activity via disruption of various signaling pathways leading to impaired cellular growth, proliferation, and survival. In preclinical studies, mTOR inhibitors use in combination with hormonal therapy has shown promising results in overcoming endocrine resistance in breast cancer cells. The role of everolimus in breast cancer was established in the Breast Cancer Trial of Oral Everolimus-2 (BOLERO-2) trial in combination with exemestane for patients with advanced metastatic hormone receptor-positive (HR+) breast cancer, who relapsed after initial hormonal manipulation. The study met its primary endpoint of significant improvement in progression free survival (PFS) with a median time to progression of 6.9 months in the combination group versus 2.8 months in exemestane group. Favorable improvements in PFS were reported across all patient subgroups regardless of age, Eastern Cooperative Oncology Group performance status, number of prior therapies, and presence of visceral metastases. Adverse events were mostly mild to moderate in severity and consistent with the known safety profile of everolimus. Major toxicities reported include stomatitis, non-infectious pneumonitis, and hyperglycemia. The purpose of this review is to discuss the role of everolimus as a valuable component in advanced metastatic breast cancer and delineate current strategies to prevent and manage the most common toxicities associated with this combination regimen.

The life, death, and attempted rebirth of bevacizumab in breast cancer.

Breast cancer is the leading cause of cancer in women. In recent years, there has been immense drug discovery and development in the field of breast cancer. Most recently, the role of vascular endothelial growth factor has moved to the treatment forefront with bevacizumab immersed into the literature as well as the media. Bevacizumab, a vascular endothelial growth factor inhibitor FDA approved for the treatment of other cancers, was first studied in metastatic breast cancer. Its use in human epidermal growth factor receptor 2-negative metastatic breast cancer ultimately failed to show an improvement in overall survival in landmark trials (E2100, AVADO, RIBBON-1 and RIBBON-2) despite its positive impact on progression-free survival. The role is yet to be determined in triple negative breast cancer as well as in the adjuvant and neoadjuvant settings. Trends begin to emerge as bevacizumab is combined with other chemotherapeutic drugs in terms of toxicities. The addition of bevacizumab is associated with an increase in the dose-limiting toxicities of the drugs combined in the regimen. As previous literature suggest, hypertension and proteinuria were also seen with the addition of bevacizumab, both of which are known adverse events. Lastly, there is a trend towards increased incidence of heart failure when bevacizumab is combined with another cardiotoxic medication, doxorubicin. This toxicity has been shown to be reversible in the majority of the cases and has a low incidence in the currently published literature.

Novel targets in the treatment of advanced melanoma: new first-line treatment options.

OBJECTIVE: To discuss the clinical efficacy and safety of ipilimumab, vemurafenib, and investigational agents for the treatment of unresectable stage III and stage IV melanoma and define current strategies of first-line treatment selection. DATA SOURCES: Literature was accessed through MEDLINE and International Pharmaceutical Abstracts (1970-November 2012) using the terms melanoma, metastatic melanoma, ipilimumab, vemurafenib, dabrafenib, and trametinib. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles published in English identified from the data sources were evaluated. Studies and abstracts including more than 10 adult patients were included in the review. DATA SYNTHESIS: Treatment options for unresectable stage III and IV melanoma are poor and have remained largely unchanged for the past 40 years. Two randomized Phase 3 clinical trials have demonstrated a significant survival benefit with the use of ipilimumab compared to a melanoma vaccine (10.1 vs 6.4 months; p = 0.003) and compared to dacarbazine (11.2 months, 95% CI 9.4-13.6 vs 9.1 months, 95% CI 7.8-10.5). Additionally, long-term follow-up has revealed cases of durable responses of greater than 3 years. Response rates of 50% and greater have been described in vemurafenib-treated patients (1 Phase 1, 1 Phase 2, and 1 Phase 3 randomized trial), although duration of response has not been fully determined. Both new agents possess unique toxicity profiles including immune-related adverse events with ipilimumab and secondary cutaneous cancers reported with vemurafenib use. CONCLUSIONS: Treatment strategies have changed for patients with advanced melanoma with the use of ipilimumab and vemurafenib as first-line agents. Increased clinical experience and further published data with these and investigational agents will guide the development of treatment algorithms outlining optimal drug selection and sequencing as well as improve management of their novel adverse events.

Bevacizumab-induced oral mucositis in background of cutaneous plaque-type psoriasis.

OBJECTIVE: To report the serial development of oral mucositis following infusion of bevacizumab in a young woman with a malignant brain tumor and history of cutaneous psoriasis. CASE SUMMARY: A 29-year-old woman with a history of active cutaneous psoriasis and a malignant glioneuronal tumor was treated with bevacizumab for 2.5 years. With each infusion of bevacizumab, she developed oral mucositis within 36 hours. She received temozolomide as part of concurrent therapy with radiation and as maintenance therapy; it was discontinued after continuous therapy for 1.5 years. Bevacizumab 10 mg/kg was added after 7 cycles of maintenance temozolomide, as the tumor had minimal response and evidence of increased perfusion with angiogenesis on imaging studies. All medication, including temozolomide, was evaluated and eventually discontinued, with the exception of bevacizumab, which remained the drug suspected of causing the mucositis. DISCUSSION: Oral mucositis is a frequent adverse effect of cytotoxic chemotherapy, but has not been reported with bevacizumab. The Naranjo probability scale indicated a probable adverse drug reaction. This likely indicates that bevacizumab is one of many drugs known to induce exacerbation of psoriatic disease. We speculate that oral mucositis developed as bevacizumab-induced generation of proinflammatory cytokines within the vascular endothelium, leading to mucosal damage and ulceration. In addition, interruption of reparative angiogenic pathways with bevacizumab likely contributed to the severity of mucositis. CONCLUSIONS: Clinicians should be aware that bevacizumab can potentially exacerbate psoriatic disease.

Transfusions increase with nationally driven reimbursement changes of erythropoiesis stimulating agents for chemotherapy-induced anemia.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) issued a national coverage determination (NCD) in July 2007, which imposed restrictions on the reimbursement of ESAs for Medicare and Medicaid beneficiaries. Since a majority of our patients are Medicare or Medicaid beneficiaries, we changed our clinical practice regarding the use of erythropoiesis stimulating agents (ESAs) to coincide with the NCD's reimbursement restriction. OBJECTIVE: To evaluate the number of transfusions in patients diagnosed with chemotherapy-induced anemia (CIA) receiving ESAs before and after the clinical practice was changed at the University of Illinois Medical Center (UIMC). METHODS: The medical records of all adult patients diagnosed with a nonmyeloid malignancy and CIA who received an ESA between July 2006 and June 2008 at the UIMC were evaluated. The patients were divided into two groups: patients in receipt of ESAs BEFORE (group 1) and AFTER (group 2). The number of transfusions, the response rates to chemotherapy and ESAs therapy, and overall survival were compared. RESULTS: Medical records for 110 patients were reviewed. More transfusions were given to patients AFTER we implemented the change in clinical practice (BEFORE 18 transfusions vs. AFTER 52 transfusions, p = 0.004). More patients responded to ESA therapy AFTER we implemented the change (67% vs. 83%, p = NS). The treatment response to chemotherapy and overall survival were similar between the two groups. CONCLUSION: The primary goal of reducing the number of transfusions in patients with CIA by administering ESAs cannot be met when clinical practice coincides with the NCD.