Mentorship Experiences Are Not All the Same: A Survey Study of Oncology Trainees and Early-Career Faculty.

PURPOSE: Physician workforce diversity can be a driver of institutional excellence, improving innovation and reducing health disparities. However, the current diversity of the hematology/oncology (HO) workforce does not reflect that of the US population. METHODS: We conducted a cross-sectional online survey of current trainees and faculty within 5 years of completing terminal training in oncology specialties. RESULTS: Of the 306 respondents, 64 (21%) were under-represented in medicine (URiM) and 161 (53%) identified as male. URiM participants were less likely to have a primary mentor (66%) than non-URiM participants (80%; P = .015). Among those who had a primary mentor, URiMs met less frequently (once every 3-6 months or less) with their mentor (19% v 7% non-URiM; P = .003). Furthermore, URiMs were more likely to report having mentors outside their own institution (47% v 40% non-URiM; P = .002) and making compromises to gain access to mentorship (36% v 23% non-URiM; P ≤ 0.001). URiMs were also less likely to apply for grants (34% v 42% non-URiM; P = .035) and awards (28% v 43% non-URiM; P = .019). In multivariable models, URiM individuals were more likely to make compromises to gain access to mentors (odds ratio [OR], 1.96; 95% CI, 1.01 to 3.82) and this remained significant for females (OR, 2.17; 95% CI, 1.26 to 3.75). CONCLUSION: URiM individuals may be less likely to have effective mentorship and apply for awards and grant support. Understanding the challenges of URiM trainees can help shape training environments in academic medicine to ensure that they are grounded in diversity, inclusion, and retention.

Dataset used in the economic evaluation trastuzumab-based regimens for HER-2 positive metastatic breast cancer patients in the Taiwanese healthcare setting.

The present data article aims to describe the input parameters for a Markov model assessing the cost-effectiveness of four treatment sequences for patients with HER-2 positive metastatic breast cancer. The model input parameters include costs for physician visits, drugs, adverse event management, computed tomography (CT) scan, laboratory tests, echocardiogram, utilities, disutilities as well as the shape and scale parameters of a log-logistic distribution used for the transition probabilities.

A cost-effectiveness analysis of trastuzumab-containing treatment sequences for HER-2 positive metastatic breast cancer patients in Taiwan.

OBJECTIVE: Treatment options for HER-2-positive metastatic breast cancer (mBC) patients have expanded markedly since trastuzumab approval in 1998. Several other regimens are now available, including pertuzumab plus trastuzumab plus docetaxel, T-DM1, capecitabine plus lapatinib, and trastuzumab plus lapatinib. This study assesses the cost-effectiveness of four treatment sequences for HER-2-positive mBC according to the Taiwanese National Health Insurance Administration (TNHIA). METHODS: Costs (U.S. Dollars) and effectiveness (quality-adjusted life years) of four treatment sequences for HER-2-positive mBC patients were examined using a Markov model over a lifetime horizon. Transition probabilities, disease progression, and probability of adverse events and survival were derived from clinical trial data. Costs and health utilities were estimated from TNHIA, Taipei Medical University Hospital, and the literature. Deterministic, probabilistic sensitivity analyses and a scenario analysis examined parameter uncertainty and accounted for drug wastage in dosage and cost calculations. RESULTS: Sequence 3 (1st line: trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: trastuzumab plus lapatinib) was the most cost-effective sequence followed by sequence 1 (1st line: pertuzumab plus trastuzumab plus docetaxel; 2nd line: T-DM1; 3rd line: capecitabine plus lapatinib), and sequence 4 (1st line: trastuzumab plus docetaxel; 2nd line: trastuzumab plus lapatinib; 3rd line: trastuzumab plus capecitabine), respectively. The model was sensitive to costs and transition probabilities, but not particularly sensitive to the wastage assumption. CONCLUSIONS: From the perspective of the TNHIA, trastuzumab plus docetaxel as 1st line followed by T-DM1 and trastuzumab plus lapatinib as 2nd and 3rd line represents the most cost-effective strategy among the four sequences considered for treating HER-2-positive mBC patients.

Cost-effectiveness of pembrolizumab as first-line therapy for advanced non-small cell lung cancer.

BACKGROUND: Anti-PD-1 immunotherapy has dramatically shifted therapeutic perspectives for advanced non-small cell lung cancer (NSCLC). We assessed cost-effectiveness of anti-PD-1 antibody pembrolizumab compared to platinum-doublet chemotherapy as first-line therapy for advanced NSCLC. METHODS: We retrieved survival, progression, and safety data comparing first-line pembrolizumab to platinum-doublets for advanced NSCLC patients with PD-L1 expression ≥50%, non-mutated EGFR, and non-translocated ALK, from KEYNOTE-024. Published United Kingdom (UK) and United States (US) costs informed incremental cost-effectiveness ratios (ICERs). Our analysis was based on a Bayesian Markov model of disease with full lifetime horizon. We estimated costs in USD and summarized effectiveness as quality-adjusted life-years (QALYs). RESULTS: Patients treated with pembrolizumab accumulated 1.80 QALYs (95% CrI 1.56-1.89), for moderate dependency between outcomes, compared to 1.06 QALYs (0.94-1.13) with chemotherapy. From a British National Health System (NHS) perspective, the ICER was $52k ($43k-$69k) per end-of-life (EoL) adjusted QALY gained, above the 42k USD threshold, while from a US cost perspective, the ICER was $49k ($40k-67k) per EoL adjusted QALY, below the hypothetical 100k USD threshold. CONCLUSIONS: Evidence suggests first-line pembrolizumab for NSCLC may be cost-effective in the US but not the UK, in spite of very similar ICER values in both countries.

Global Health Perspective in Sarcomas and Other Rare Cancers.

Sarcomas, rare and heterogenous malignancies that comprise less than 1% of all cancers, have poor outcomes in the metastatic and refractory setting. Their management requires a multidisciplinary approach that consists of medical and surgical oncologists, radiation oncologists, and pathologists as well as ancillary support. In addition to systemic treatments, most patients will require surgical resection and radiation therapy, which mandates the use of the latest technologies and specialized expertise. Management guidelines have been developed in high-income countries, but their applicability in low-income countries, where resources may be limited, remains a challenge. In this article, we propose the best possible evidence-based practices specifically for income-constrained settings to overcome this challenge. In addition, we review the different methods that can be used in low-income countries to access new and expensive treatments, which often times carry prohibitive costs for these areas.

Cost-effectiveness of Osimertinib in the First-Line Treatment of Patients With EGFR-Mutated Advanced Non-Small Cell Lung Cancer.

Importance: The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. Objective: The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. Design, Setting, and Participants: For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives. Main Outcomes and Measures: The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first- or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC. Results: In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first- and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were $226 527 vs erlotinib, $231 123 vs gefitinib, and $219 874 vs afatinib. In Brazil, the ICERs were $162 329, $180 804, and $175 432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from $84 342 to $859 771). Osimertinib price adjustments to the FLAURA trial data improved cost-effectiveness. For example, a discount of 10% on osimertinib acquisition cost was associated with a 20% decreased ICER compared with the base case ICER, and a discount of 20% on osimertinib acquisition cost was associated with a 40% decreased ICER compared with the base case ICER. Conclusions and Relevance: At current costs, by World Health Organization cost-effectiveness threshold criteria, osimertinib is not cost-effective for first-line therapy of EGFR-mutated NSCLC in either the United States or Brazil.

Chimeric antigen receptor T cells, a savior with a high price.

Chimeric antigen receptor (CAR) T cells represent a medical and scientific breakthrough that may represent a paradigm for the future of personalized medicine in the age of cancer immunotherapy. As with many new cancer agents, such novel and incredible results come with a high price. At the time of the writing of this article, there are two CAR T cells available, Kymriah, produced by Novrtis with a price tag of US$475,000 and Yescarta produced by Gilead Pharmaceuticals with a price tag of US$373,000, neither price including the required hospital admission in order to administer the agent in addition to potential treatment of side effects. There are several issues that are imperative to recognize when understanding the high cost, however the two more pertinent issues are low availability of the agent and no billing code. While only approved for less than a year, there are thoughts about how to bring the price down with more approved CAR T cells and more center with the ability to administer this therapy, however results may be years away before they are realized. In the short term, insurance companies are grappling over how to pay for CAR T therapy, with one of the biggest voids concerning the absence of a billing code for CAR T cells. Regardless, its high price tag highlights moral issues underlying value-based payments and whether the treatment is worth the cost while evaluating the juxtaposition of life years and monetary values. As CAR T cells expand the boundaries of immunotherapy with extraordinary results, the need for a lower price in combination for more availability of CAR T cells will grow until some of these fundamental issues are addressed.

The Concept of Biosimilars: From Characterization to Evolution-A Narrative Review.

Biologic agents are currently the fastest emerging segment of drug expenditure. Unlike chemically synthesized small-molecule drugs, biologics are more complex, medicinal products produced by a living organism. They have become part of the standard of care in the treatment of a large variety of diseases, such as growth disorders, autoimmune diseases, cancer, cardiovascular illnesses, hemophilia, and rare genetic conditions, to name a few. Biosimilars, which are copies of biologics that are highly similar, were introduced in the market with an aim to offer efficacy that is not clinically different from the originator or reference product, at lower prices. We aim to clarify the concept of biosimilar, from definitions, history, market entry, challenges faced, and future evolution. For that purpose, we performed a literature search on the sites of the medicines regulatory agencies and PubMed from 1990 to 2014 with the keywords "biosimilars," "market," and "regulatory." In 2006, the first biosimilar, somatropin [rDNA origin], was marketed and led the way for biosimilar drug manufacturing. As a result, manufacturers have entered a diversified competition, facing challenges in manufacturing these complex agents, such as immunogenicity and efficiency. Biosimilars are set to evolve differently in various markets, namely the U.S., Japan, the European Union, and the "pharmerging" economies. IMPLICATIONS FOR PRACTICE: This article highlights the importance of biosimilars, as a cost-cutting strategy, in the delivery of state-of-the-art health care in developing countries, at a fraction of what a reference biological agent would cost.

Economic evaluation of sequencing strategies in HER2-positive metastatic breast cancer in Mexico: a contrast between public and private payer perspectives.

PURPOSE: Breast cancer is the most common malignancy among women in Mexico. A large proportion of Mexican patients present with advanced disease, and 25% have HER2-positive tumors. We performed a cost-effectiveness analysis of different sequencing strategies of HER2-targeted agents in Mexico according to various payer perspectives. METHODS: A Markov model was constructed to evaluate the cost-effectiveness of four different HER2-targeted treatment sequences among patients with HER2-positive metastatic breast cancer treated in Mexico according to three public and one private payer perspectives. Patients were followed weekly over their remaining life expectancies within the model. Health states considered were progression-free survival (PFS) 1st-3rd lines, and death. Transition probabilities between states were based on published trials. Cost data were obtained from official publications from Mexican healthcare institutions. The evaluated outcomes were PFS, OS, costs, QALYs, and incremental cost effectiveness ratio (ICER). RESULTS: In the public payer perspective, sequences containing pertuzumab or T-DM1 were not cost-effective when compared with a sequence including the combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab, even when utilizing alternate definitions for willingness to pay thresholds. In the private payer perspective, a sequence containing T-DM1 but not pertuzumab proved cost-effective at a lower clinical effectiveness. CONCLUSIONS: In Mexico, the use of at least three lines of trastuzumab in combination with other therapies, but not with pertuzumab or TDM-1, represents the most cost-effective option for patients covered by the public healthcare system, and this sequence should be made available for all patients.

Global Health Initiatives of the International Oncology Community.

Cancer has become one of the leading causes of morbidity and mortality in low- and middle-income countries (LMICs), where 60% of the world's total new cases are diagnosed. The challenge for effective control of cancer is multifaceted. It mandates integration of effective cancer prevention, encouraging early detection, and utilization of resource-adapted therapeutic and supportive interventions. In the resource-constrained setting, it becomes challenging to deliver each service optimally, and efficient allocation of resources is the best way to improve the outcome. This concept was translated into action through development of resource-stratified guidelines, pioneered by the Breast Health Global Initiative (BHGI), and later adopted by most oncology societies in an attempt to help physicians deliver the best possible care in a limited-resource setting. Improving outcome entails collaboration between key stakeholders, including the pharmaceutical industry, local and national health authorities, the World Health Organization (WHO), and other nonprofit, patient-oriented organizations. Therefore, we started to observe global health initiatives-led by ASCO, the Union for International Cancer Control (UICC), and the WHO-to address these challenges at the international level. This article discusses some of these initiatives.

Cost-effectiveness analysis of 1st through 3rd line sequential targeted therapy in HER2-positive metastatic breast cancer in the United States.

PURPOSE: Based on available phase III trial data, we performed a cost-effectiveness analysis of different treatment strategies that can be used in patients with newly diagnosed HER2-positive metastatic breast cancer (mBC). PATIENTS AND METHODS: We constructed a Markov model to assess the cost-effectiveness of four different HER2 targeted treatment sequences in patients with HER2-positive mBC treated in the U.S. The model followed patients weekly over their remaining life expectancies. Health states considered were progression-free survival (PFS) 1st to 3rd lines, and death. Transitional probabilities were based on published phase III trials. Cost data (2015 US dollars) were captured from the U.S. Centers for Medicare and Medicaid Services (CMS) drug payment table and physician fee schedule. Health utility data were extracted from published studies. The outcomes considered were PFS, OS, costs, QALYs, the incremental cost per QALY gained ratio, and the net monetary benefit. Deterministic and probabilistic sensitivity analyses assessed the uncertainty around key model parameters and their joint impact on the base-case results. RESULTS: The combination of trastuzumab, pertuzumab, and docetaxel (THP) as first-line therapy, trastuzumab emtansine (T-DM1) as second-line therapy, and lapatinib/capecitabine third-line resulted in 1.81 QALYs, at a cost of $335,231.35. The combination of trastuzumab/docetaxel as first line without subsequent T-DM1 or pertuzumab yielded 1.41 QALYs, at a cost of $175,240.69. The least clinically effective sequence (1.27 QALYs), but most cost-effective at a total cost of $149,250.19, was trastuzumab/docetaxel as first-line therapy, T-DM1 as second-line therapy, and trastuzumab/lapatinib as third-line therapy. CONCLUSION: Our results suggest that THP as first-line therapy, followed by T-DM1 as second-line therapy, would require at least a 50 % reduction in the total drug acquisition cost for it to be considered a cost-effective strategy.

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

Economic analyses in squamous cell carcinoma of the head and neck: a review of the literature from a clinical perspective.

The purpose of this review was to describe cost-effectiveness and cost analysis studies across treatment modalities for squamous cell carcinoma of the head and neck (SCCHN), while placing their results in context of the current clinical practice. We performed a literature search in PubMed for English-language studies addressing economic analyses of treatment modalities for SCCHN published from January 2000 to March 2013. We also performed an additional search for related studies published by the National Institute for Health and Clinical Excellence in the United Kingdom. Identified articles were classified into 3 clinical approaches (organ preservation, radiation therapy modalities, and chemotherapy regimens) and into 2 types of economic studies (cost analysis and cost-effectiveness/cost-utility studies). All cost estimates were normalized to US dollars, year 2013 values. Our search yielded 23 articles: 13 related to organ preservation approaches, 5 to radiation therapy modalities, and 5 to chemotherapy regimens. In general, studies analyzed different questions and modalities, making it difficult to reach a conclusion. Even when restricted to comparisons of modalities within the same clinical approach, studies often yielded conflicting findings. The heterogeneity across economic studies of SCCHN should be carefully understood in light of the modeling assumptions and limitations of each study and placed in context with relevant settings of clinical practices and study perspectives. Furthermore, the scarcity of comparative effectiveness and quality-of-life data poses unique challenges for conducting economic analyses for a resource-intensive disease, such as SCCHN, that requires a multimodal care. Future research is needed to better understand how to compare the costs and cost-effectiveness of different modalities for SCCHN.

Pharmacoeconomic issues in head and neck oncology.

PURPOSE OF REVIEW: Despite medical advances, the global incidence, morbidity and mortality associated with head and neck cancer remain high. Pharmacoeconomic analyses of chemotherapeutic options commonly used by head and neck oncologists are reviewed in context with current clinical practice. RECENT FINDINGS: From the British health system perspective, cetuximab with radiotherapy in locally advanced head and neck was found to be cost-effective compared to single modality radiotherapy in patients with a good performance status, and in whom platinum agents are contraindicated. Induction chemotherapy with the three-drug regimen docetaxel, cisplatin and 5-fluorouracil is considered cost-effective when compared to the doublet cisplatin-5-fluorouracil from the British and Italian perspectives. However, it is unclear whether induction chemotherapy per se is effective when compared to chemoradiotherapy. Cetuximab with chemotherapy is not recommended from a British health perspective for patients with metastatic/recurrent disease, whereas it is the preferred regimen in commonly used guidelines in the US, where economic evaluations are not incorporated in the drug approval process. SUMMARY: The critical assessment and utilization of pharmacoeconomic evaluations, always in context with current clinical practice, should be further performed and promoted in head and neck oncology.

Management of colon cancer: resource-stratified guidelines from the Asian Oncology Summit 2012.

Colon cancer is seen with increasing frequency in the Asia-Pacific region, and it is one of the most important causes of cancer mortality worldwide. This article reviews the available evidence for optimum management of colon cancer-in particular, with respect to screening and early detection of colon cancer, laparoscopic surgical treatment, adjuvant treatment of individuals with high-risk stage II and stage III cancer, palliative treatment of patients with metastatic disease, and management of resectable and potentially resectable metastases-and how these strategies can be applied in Asian countries with different levels of health-care resources and economic development, stratified by basic, limited, enhanced, and maximum resource levels.

Cost-effectiveness of epidermal growth factor receptor mutation testing and first-line treatment with gefitinib for patients with advanced adenocarcinoma of the lung.

BACKGROUND: Epidermal growth factor receptor (EGFR) testing and first-line therapy with gefitinib for patients with activating mutations is quickly becoming the standard option for the treatment of advanced lung adenocarcinoma. Yet, to date, little is known about the cost-effectiveness of this approach. METHODS: A decision-analytic model was developed to determine the cost-effectiveness of EGFR testing and first-line treatment with gefitinib for those patients who harbor activating mutations versus standard care, which includes first-line treatment with chemotherapy followed by gefitinib as second-line treatment. The model uses clinical and outcomes data from randomized clinical trials and societal costs from Singapore cancer centers. Health effects were expressed as quality-adjusted life-years. All costs and cost-effectiveness ratios were expressed in 2010 Singapore dollars. Sensitivity and different scenarios analyses were conducted. RESULTS: EGFR testing and first-line treatment with gefitinib is a dominant strategy (with lower costs and greater effectiveness) compared with standard care. Because the primary savings result from not providing gefitinib to those who are not likely to benefit, this finding holds regardless of the prevalence of activating mutations. In a secondary analysis, first-line treatment with gefitinib was also dominant when compared with first-line chemotherapy in patients with activating EGFR mutations. CONCLUSIONS: This strategy can be considered a new standard of care and should be of great interest for health care payers and decision makers in an era in which our greatest challenge is to balance hard-won and incremental, yet small, improvements in patient outcomes with exponentially rising costs.