Clinical and economic outcomes of adding [18F]FES PET/CT in estrogen receptor status identification in metastatic and recurrent breast cancer in the US.

BACKGROUND AND OBJECTIVES: Correct identification of estrogen receptor (ER) status in breast cancer (BC) is crucial to optimize treatment; however, standard of care, involving biopsy and immunohistochemistry (IHC), and other diagnostic tools such as 2-deoxy-2-[18F]fluoro-D-glucose or 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG), can yield inconclusive results. 16α-[18F]fluoro-17ß-fluoroestradiol ([18F]FES) can be a powerful tool, providing high diagnostic accuracy of ER-positive disease. The aim of this study was to estimate the budget impact and cost-effectiveness of adding [18F]FES PET/CT to biopsy/IHC in the determination of ER-positive status in metastatic (mBC) and recurrent breast cancer (rBC) in the United States (US). METHODS: An Excel-based decision tree, combined with a Markov model, was developed to estimate the economic consequences of adding [18F]FES PET/CT to biopsy/IHC for determining ER-positive status in mBC and rBC over 5 years. Scenario A, where the determination of ER-positive status is carried out solely through biopsy/IHC, was compared to scenario B, where [18F]FES PET/CT is used in addition to biopsy/IHC. RESULTS: The proportion of true positive and true negative test results increased by 0.2 to 8.0 percent points in scenario B compared to scenario A, while re-biopsies were reduced by 94% to 100%. Scenario B resulted in cost savings up to 142 million dollars. CONCLUSIONS: Adding [18F]FES PET/CT to biopsy/IHC may increase the diagnostic accuracy of the ER status, especially when a tumor sample cannot be obtained, or the risk of a biopsy-related complication is high. Therefore, adding [18F]FES PET/CT to biopsy/IHC would have a positive impact on US clinical and economic outcomes.

Final overall survival analysis of the phase 3 HERITAGE study demonstrates equivalence of trastuzumab-dkst to trastuzumab in HER2-positive metastatic breast cancer.

PURPOSE: The phase 3 HERITAGE trial demonstrated that the biosimilar trastuzumab-dkst is well tolerated with similar efficacy (measured by overall response rate [ORR] and progression-free survival [PFS]) compared with originator trastuzumab combined with taxane followed by monotherapy in patients with HER2-positive metastatic breast cancer (MBC). Herein, we present final overall survival (OS) from HERITAGE. METHODS: HERITAGE is a multicenter, double-blind, randomized, parallel-group study. Patients were randomized 1:1 to receive trastuzumab-dkst or trastuzumab plus taxane followed by continued monotherapy until disease progression. Overall survival was to be assessed at 36 months or after 240 deaths, whichever occurred first, as observed from time of randomization of last patient. RESULTS: At the final analysis (36 months), 242 patients in the intention-to-treat population had died during the study: 116 and 124 in the trastuzumab-dkst and trastuzumab groups, respectively, and 1 untreated patient from each treatment group. Median OS by Kaplan-Meier analysis was 35.0 months with trastuzumab-dkst and 30.2 months with trastuzumab. Evaluation of PFS showed a median of 11.1 months in both treatment groups. No new safety concerns were reported from week 48 until the end of the survival follow-up. CONCLUSION: This is the first phase 3 trial of a trastuzumab biosimilar to report long-term survival data similar to originator trastuzumab in patients with MBC. The comparable long-term OS between the trastuzumab-dkst and originator trastuzumab groups further supports the similarity of trastuzumab-dkst with originator trastuzumab and establishes trastuzumab-dkst as a safe and effective treatment option for patients with HER2-positive MBC. ClinicalTrials.gov NCT02472964; 6/16/2015.

Cost-efficiency and expanded access modeling of conversion to biosimilar trastuzumab-dkst with or without pertuzumab in metastatic breast cancer.

AIMS: To investigate the cost-efficiency and budget-neutral expanded access of biosimilar intravenous trastuzumab-dkst versus reference intravenous (trastuzumab-IV) and subcutaneous trastuzumab (trastuzumab-SC) (with/without pertuzumab) in metastatic breast cancer (MBC). METHODS: Economic simulation modeling in a panel of 1,000 MBC patients to estimate: 1) cost-savings by conversion from trastuzumab-IV or trastuzumab-SC to trastuzumab-dkst at 10-100% conversion rates in 3 weight groups: first quartile (Q1:62.2 kg), median (73.1 kg), third quartile (Q3:88.6 kg), and 2) budget-neutral expanded access to trastuzumab-dkst from cost-savings. RESULTS: In monotherapy, conversion (%) from trastuzumab-IV generates one-year cost-savings from $2,272,189 (Q1;10%) to $31,506,804 (Q3;100%) and from trastuzumab-SC monotherapy savings range from $2,071,277 (Q3;10%) to $35,775,475 (Q1;100%). In combination with pertuzumab, trastuzumab-dkst is cost-efficient in all patient weights with one-year savings over trastuzumab-IV up to $32,662,714 (Q3;100%) and over trastuzumab-SC up to $35,322,461 (Q1;100%). Savings from conversion from trastuzumab-IV monotherapy could provide between 3,087 (Q1;10%) and 30,911 (Q3;100%) additional trastuzumab-dkst doses-enough to treat 58 to 583 patients for one year. Conversion from trastuzumab-SC monotherapy could provide between 1,559 (Q3;10%) and 48,598 (Q1;100%) additional trastuzumab-dkst doses or 38 to 918 additional one-year treatments with trastuzumab-dkst. In combination with pertuzumab, conversion from trastuzumab-IV could provide from 311 (Q1;10%) to 3,939 (Q3;100%) maintenance doses (pertuzumab + trastuzumab-dkst) or 17 to 210 additional one-year regimens (all agents). Savings from conversion from trastuzumab-SC could expand access to 226 (Q3;10%) to 4,782 (Q1;100%) additional maintenance doses or 12 to 254 one-year regimens. CONCLUSIONS: This first cost-efficiency and expanded access study of biosimilar therapeutic cancer agents shows that trastuzumab-dkst is cost-efficient over trastuzumab-IV and trastuzumab-SC across all patient weights in both monotherapy and combination with pertuzumab and paclitaxel. These cost savings could provide more patients with trastuzumab-dkst treatment on a budget-neutral basis.

Conversion from pegfilgrastim with on-body injector to pegfilgrastim-jmdb: cost-efficiency analysis and budget-neutral expanded access to prophylaxis and treatment.

AIMS: Therapeutic guidelines recommend prophylaxis against chemotherapy-induced (febrile) neutropenia (CIN/FN). Pegfilgrastim (Neulasta), biosimilar pegfilgrastim-jmdb (Fulphila), and pegfilgrastim with on-body injector (OBI; Neulasta Onpro) are options for CIN/FN prophylaxis. We aimed to simulate the cost-savings and budget-neutral expanded access to CIN/FN prophylaxis or anticancer treatment achieved through conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb and to evaluate the economic impact of FN-related hospitalization costs due to pegfilgrastim-OBI failure. METHODS: Cost-savings from conversion from pegfilgrastim-OBI to biosimilar pegfilgrastim-jmdb were simulated in a panel of 15,000 patients with cancer from the US payer perspective. The primary analyses included conversion rates of 10% to 100%. Adjusted analyses also considered OBI device failure rates of 1% to 7% and associated costs of FN-related hospitalization. Simulations of budget-neutral expanded access to prophylaxis with pegfilgrastim-jmdb or to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for diffuse large B-cell lymphoma (DLBCL) were also performed. RESULTS: In a 15,000-patient panel, conversion from pegfilgrastim-OBI to pegfilgrastim-jmdb resulted in cost-savings ranging from $481,259 (10% conversion) to $4,812,585 (100% conversion) in a single cycle. Over 6 cycles at 100% conversion, savings were $28,857,510 and could provide 9,191 additional doses of pegfilgrastim-jmdb or 4,463 cycles of R-CHOP to patients with DLBCL. Adjusted for OBI failure, cost-savings over 6 cycles ranged from $2,935,565 (10% conversion; pegfilgrastim-OBI failure rate of 1%) to $32,236,499 (100% conversion; 7% failure). These cost-savings could provide 943 doses of pegfilgrastim-jmdb or 454 doses of R-CHOP (10% conversion; 1% pegfilgrastim-OBI failure) or provide 10,261 doses of pegfilgrastim-jmdb or 4,982 cycles of R-CHOP (100% conversion; 7% failure). CONCLUSION: Conversion from pegfilgrastim to pegfilgrastim-jmdb is associated with significant cost-savings which increase markedly when also accounting for pegfilgrastim-OBI failure and associated FN-related hospitalizations. These general and failure-related cost-savings could be allocated on a budget-neutral basis to provide more patients with additional CIN/FN prophylaxis or antineoplastic treatment.

Intravenous and subcutaneous formulations of trastuzumab, and trastuzumab biosimilars: implications for clinical practice.

Trastuzumab is a biologic therapy indicated for the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer and metastatic gastric cancer. Trastuzumab was originally approved as an intravenous (IV) formulation but has since been developed for subcutaneous (SC) administration for patients with HER2-positive breast cancer. Both formulations demonstrate generally comparable pharmacological and clinical profiles. Therefore, when deciding between treatment options, factors such as the route of administration, patient preference, value and cost must be considered. Studies comparing IV with SC trastuzumab indicate that each formulation offers unique advantages to patients depending on their individual needs. Concurrent with the development of SC trastuzumab, IV trastuzumab biosimilars comprise another treatment option that, in view of their reduced cost, might improve patient access and increase cost-effectiveness for healthcare providers and payers. In this review, we seek to raise awareness of the current options available for trastuzumab so that healthcare providers can optimally treat patients according to their individual situations and preferences.

Parámetros de práctica para el manejo del dolor en cáncer: Grupo de Consenso para el Manejo del Dolor en Cáncer / Practice guidelines for cancer pain management: Task Force for Cancer Pain Management

El dolor por cáncer es un problema frecuente en nuestro medio, se presenta en 80 a 90 % de los pacientes y en aproximadamente 90 % de ellos se resuelve con medidas relativamente sencillas. No obstante, aproximadamente 40 % de los pacientes se encuentra insatisfecho con el médico o la enfermera respecto al manejo de su dolor. Por tal motivo, se convocó a un grupo de consenso con la finalidad de generar parámetros de práctica clínica fundamentados en la evidencia publicada y en la opinión de los expertos. Este grupo estuvo integrado por 31 médicos líderes de opinión es este campo, quienes con base en 599 documentos emitieron esta serie de recomendaciones, identificadas cada una según su nivel de evidencia.

Cancer pain is a frequent medical problem in our society. This syndrome affects from 80 to 90% of cancer patients and can be solved with relatively simple measures in 90% of the cases. Approximately 40% of cancer patients reported to be unsatisfied with the physician or nurse about their pain management. For these reasons, we gathered a task force in order to generate practice guidelines based on medical evidence and on the opinion of experts in this area. These guidelines were generated by a task force of 31 physicians who were leaders in this field and based on 599 papers selected by a previous literature search. This group evaluated the results of this search in three work sessions, during which a level of evidence was assigned to each recommendation.

Angiogenesis in the bone marrow of patients with breast cancer.

PURPOSE: Pathologic angiogenesis has been correlated with tumor growth, dissemination, metastasis, and prognosis in solid tumors including breast cancer. Angiogenesis has also been implicated in the pathophysiology of, and shown to be a therapeutic target in tumors arising in the bone marrow. The status of angiogenesis in the bone marrow of breast cancer patients is unknown. The aim of this study was to estimate the extent of bone marrow angiogenesis in this subset of patients. EXPERIMENTAL DESIGN: We studied 42 women with breast cancer in whom a bone marrow biopsy was done. Bone marrow samples were sorted according to their infiltration status by breast cancer cells. In all bone marrow sections, blood vessels were highlighted by staining endothelial cells with an antibody directed against the CD34-related antigen. A hematopathologist blind to the status of infiltration of breast cancer did the bone marrow vessel count. RESULTS: Nineteen patients (45%) had bone marrow metastasis. The bone marrow microvessel density was significantly higher in patients with bone marrow metastases compared with patients without bone marrow metastases (P < 0.0005). Median bone marrow microvessel density was 2 for the negative bone marrow group, and 15 for the positive bone marrow group. An increased microvessel density was correlated with presence of disease at last follow-up. CONCLUSIONS: This is the first study showing that bone marrow microvessel density is significantly higher in breast cancer patients with bone marrow metastases, when compared with breast cancer patients without evidence of bone marrow metastatic disease. Further research is needed to shed light into the prognostic and therapeutic relevance of this finding.

Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer.

PURPOSE: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. EXPERIMENTAL DESIGN: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. RESULTS: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. CONCLUSIONS: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs.

Síndromes paraneoplásicos neurológicos / Neurologic paraneoplasic syndromes

Los síndromes paraneoplásicos neurológicos son un grupo de entidades causadas por los efectos a distancia de un tumor, y dado que pueden afectar cualquier porción del sistema nervioso, se presentan como cuadros neurológicos. Estas entidades son condiciones poco frecuentes causadas por respuestas inmunes contra antígenos tumorales que tienen una reacción cruzada con antígenos neuronales. En esta revisión se estudian los mecanismos propuestos para explicar su etiopatogenia, haciendo hincapié en la reacción autoinmune hacia antígenos onconeurales. En esta revisión se analizan las manifestaciones clínicas de los síndromes paraneoplásicos neurológicos, las neoplasias a las que se asocian así como la importancia de establecer un diagnóstico; tratamos de recalcar el valor de estudio de los mismos, pues pueden ser la primera manifestación de malignidad.