Cost-effectiveness analysis of ribociclib plus fulvestrant for hormone receptor-positive/human EGF receptor 2-negative breast cancer.

Aim: To evaluate the cost-effectiveness of ribociclib plus fulvestrant versus fulvestrant in hormone receptor-positive/human EGF receptor 2-negative advanced breast cancer. Materials & methods: A three-state Markov model was developed to evaluate the costs and effectiveness over 10 years. Direct costs and utility values were obtained from previously published studies. We calculated incremental cost-effectiveness ratio to evaluate the cost-effectiveness at a willingness-to-pay threshold of $150,000 per additional quality-adjusted life year. Results: The incremental cost-effectiveness ratio was $1,073,526 per quality-adjusted life year of ribociclib plus fulvestrant versus fulvestrant. Conclusions: Ribociclib plus fulvestrant is not cost-effective versus fulvestrant in the treatment of advanced hormone receptor-positive/human EGF receptor 2-negative breast cancer. When ribociclib is at 10% of the full price, ribociclib plus fulvestrant could be cost-effective.

Cost-effectiveness of six months versus 1-year adjuvant trastuzumab in HER2 positive early breast cancer in Egypt.

Introduction: Breast cancer is the most prevalent cancer among women in Egypt. Trastuzumab is administered with chemotherapy for patients with HER2-positive advanced breast cancer (HER2 + ve ABC) in the metastatic and adjuvant settings resulting in improved treatment outcomes, and long-term follow-up. Some studies have evaluated whether equivalent outcomes can be achieved with reduced treatment duration. This study evaluates the cost-effectiveness of 6-month versus 1-year trastuzumab treatments from payer perspective over a 10 year time horizon.Methods: A half-cycle corrected Markov model was developed with five mutually exclusive health states; patient with HER2 +ve ABC, disease-free survival (DFS), local or regional relapse, metastatic relapse, and death. A cycle length of 6 months was applied, direct medical costs including cost of treatments, day-care, surgery, health states and follow-up visits were collected, and indirect costs such as lost productivity were not estimated. The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted.Results: Among the HER2 +ve ABC patient population in Egypt, the total QALYs of the 6-month trastuzumab were estimated to be 2.99 compared with 2.93 for the 1-year trastuzumab which resulted in a difference of 0.06 QALYs. The total costs were EGP 271,647 ($106,947) and EGP 381,248 ($150,097), respectively. These costs yielded an ICER of -109,600 EGP/QALY (-43,149 $/QALY) for the 6-month trastuzumab. The 6-month trastuzumab is a dominant strategy when compared to 1-year trastuzumab, resulting in improved effectiveness at a reduced cost. All analyses results confirmed the dominance of 6-month trastuzumab and our model robustness.Conclusions: This study concluded that 6-month trastuzumab is a cost-effective option when compared to 1-year trastuzumab in patients with HER2 +ve ABC in Egypt. Our findings provide health care decision makers with additional insights to best allocate available resources concurrently with the improvement of the Egyptian patient's outcomes.

Assessment of two different HER2 scoring systems and clinical relevance for colorectal cancer.

Although the positivity of human epidermal growth factor receptor 2 (HER2) is low in colorectal cancer (CRC), anti-HER2 is becoming a new target therapy in metastatic colorectal cancer (mCRC). However, assessment of the HER2 scoring system was still not established in CRC. The purpose of our study was to evaluate HER2 status and its correlation with clinicopathological characteristics and survival according to the HER2 diagnostic criteria for gastroesophageal adenocarcinoma (GEA criteria) and the HERACLES diagnostic criteria (HERACLES criteria) in a large cohort of Chinese CRC patients. The HER2 positivity was 2.9% (43/1490) and 2.6% (39/1490) in CRCs based on the GEA criteria and the HERACLES criteria, and 3.7% (9/243) in mCRC according to both criteria. HER2 status was associated with primary tumor location (P = 0.037), regional lymph node metastasis (P = 0.035), and TNM stage (P = 0.022) in CRCs based on the HERACLES criteria. No such association was found based on the GEA criteria. Furthermore, HER2 positive only presented in patients with RAS gene wild type (P = 0.001). Significant difference was only observed between the HER2-positive and HER2-negative groups in terms of disease-free survival for stage II-III CRCs (P = 0.048) according to the HERACLES criteria, but not based on the GEA criteria. Our findings suggest that the frequency of HER2 overexpression or amplification was low in Chinese CRC patients, and provide a rationale for further evaluation of HER2 in CRC based on the HERACLES criteria and the HER2 diagnostic criteria for gastroesophageal adenocarcinoma.

Syndecan-1 could be added to hormonal receptors and HER2/neu in routine assessment of invasive breast carcinoma, relation of its expression to prognosis and clinicopathological parameters.

INTRODUCTION: Syndecan-1 is heparan sulfate proteoglycans (HSPGs) that is used as coreceptors for signaling of growth factors. The comprehensive effect of syndecan-1 is to augment receptor stimulation at little ligand concentrations. THE GOAL OF THIS RESEARCH: is to study syndecan-1 expression in breast carcinoma and its value in predicting the prognosis in comparison to other clinicopathological parameters. MATERIAL &METHODS: immunohistochemistry study for syndecan-1 is done on 103 cases of invasive breast carcinoma. Its expression is assessed and correlated to other clinicopathological parameters and prognosis. RESULTS: overexpression was significantly related to high histologic grade (p = 0.001), large tumor size (p = 0.043), HER2-positive status (p = 0.001), and ER&PR-negative status (p = 0.001). It was also have a negative impact on the overall survival (p=0.012) and disease free survival (p = 0.009). Syndecan-1 expression showed weak positive correlation with Her 2 expression (Correlation Coefficient (co): 0.332, p = 0.001). CONCLUSION: syndecan-1 is a good predictor of poor overall survival and recurrence/ metastasis free survival. It is associated with aggressive phenotype as HER2 enriched and Triple negative rather than luminal subtypes of breast carcinoma. So it can be added to the hormonal receptors and HER 2 assay in the routine management of invasive breast cancer after confirmation on a more larger study.

Treatment and Monitoring Patterns Among Premenopausal Women with HR+/HER2- Advanced Breast Cancer.

INTRODUCTION: Premenopausal women with hormone receptor positive (HR+) and human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (aBC) often present with aggressive tumor types that lead to poor prognosis, high rates of recurrence, and mortality. Although clinical guidelines provide evidence-based recommendations for optimal treatment and monitoring, there is a dearth of information regarding treatment and monitoring patterns in clinical practice. In this study, we describe treatment and monitoring patterns among premenopausal women with HR+/HER2- aBC in real-world practice. METHODS: A large US claims database was used to describe treatment patterns for patients in first, second, and third lines of therapy. Treatment monitoring included complete blood count (CBC), liver function test (LFT), and electrocardiogram (EKG) monitoring, described for the first three lines of therapy, and separately for patients receiving endocrine monotherapy (ET) and chemotherapy. RESULTS: Among 3203 patients, chemotherapy was the most common treatment used in first-line (63.6%) and second-line therapy (66.9%). ET was used in 34.4, 30.1, and 73.6% of patients in first, second, and third lines of therapy, respectively. The two most common treatment sequences were a single line of ET (27.3%), and two consecutive lines of chemotherapy followed by a line of ET (19.3%). Patients receiving chemotherapy were monitored with CBC on average more than two times per month, and for LFT one to two times per month. Patients receiving ET were monitored with CBC and LFT on average once every 2-3 months. Overall, approximately 20% of patients were monitored with an EKG at some point during each line of therapy. CONCLUSION: A considerable proportion of premenopausal women with aBC received first- and second-line chemotherapy, which appears inconsistent with current clinical guidelines. The observed treatment heterogeneity points to a lack real-world consensus on the management of premenopausal women with HR+/HER2- aBC. FUNDING: Novartis Pharmaceuticals Corporation.

Assessment of the methods used to detect HER2-positive advanced extramammary Paget's disease.

The human epidermal growth factor receptor 2 (HER2) is recognized as an oncogene as well as a therapeutic target in various cancers. Certain patients with advanced extramammary Paget's disease (EMPD) have also been reported to express HER2, which is therefore considered a therapeutic target for EMPD. However, an accurate methodology to determine HER2-positive EMPD has not been established. To assess the optimal methods for detection of HER2-positive EMPD, 73 EMPD samples were analyzed by immunohistochemical (IHC) staining, fluorescence in situ hybridization (FISH), and the HER2 testing algorithm for breast cancer of the American Society of Clinical Oncology/College of American Pathologists, which combined the results of IHC staining and FISH. The results showed discordance in the rate of positive IHC staining and FISH results. While 68.6% (24/35) of the metastatic samples showed equivocal or positive IHC staining, only 37.1% (13/35) were positive by FISH. To assess the accuracy of these methods, the degree of HER2 expression detected by each method was correlated with the staining profiles of activated downstream signaling pathways involving phosphorylated p44/42 MAPK (Thr202/Tyr204) (p-ERK1/2) and phosphorylated AKT (Ser473) (p-AKT). Among 16 lymph node metastasis samples, all HER2-positive samples as determined by the testing algorithm stained positively for both p-ERK1/2 and p-AKT. On the other hand, 10-14.3% of the samples determined by FISH or IHC showed negative staining for p-ERK1/2 and p-AKT. The results showed that combining the results of IHC and FISH according to the HER2 testing algorithm is a useful method for accurately evaluating HER2-positive EMPD.

The Assessment of HER2 Gene Status by Fluorescence In Situ Hybridization in Invasive Breast Carcinomas With Equivocal HER2 Immunostaining: Experience From a Single Institution.

BACKGROUND: A subset of breast carcinomas harbors overexpression of the human epidermal growth factor receptor 2 (HER2). Fluorescence in situ hybridization (FISH) should be performed in breast carcinomas with equivocal HER2 immunostaining (immunohistochemistry [IHC] HER2 2+). The aim of our study is to investigate clinicopathologic factors associated with HER2 status in breast invasive carcinomas with IHC HER2 2+ through FISH analysis. METHODS: This is a retrospective study including the FISH analysis of 111 patients with invasive breast carcinomas with equivocal HER2 immunostaining. RESULTS: The mean age was 49.51 ± 10.48 years, and invasive breast carcinoma of no special type was the most histological type in our study (96.4%). Most patients had tumors positive for hormones receptors (88.2% positive for estrogen receptor and 81.4% for progesterone receptor). On FISH, the HER2 amplification rate was 22.5%. There was no significant association of HER2 status with any clinicopathologic factors ( P > .05). CONCLUSIONS: Our study shows that there are no reliable clinicopathologic factors to predict the HER2 status in breast tumors with equivocal HER2 immunostaining, supporting the necessary usage of FISH in such circumstances.

Costs of subcutaneous and intravenous administration of trastuzumab for patients with HER2-positive breast cancer.

AIM: Trastuzumab is available in an intravenous (iv.) and a subcutaneous (sc.) formulation. The objective of this study was to estimate the costs of administration of iv. and sc. trastuzumab treatment. MATERIALS & METHODS: Via interviews, we identified all the activities associated with iv. and sc. administration. The outcome was time estimates. To estimate the administration costs, the time estimates were valued by average gross wages. RESULTS: The iv. administration takes longer time as infusion time is longer (25 or 85 min). The iv. administration is associated with higher cost for 17 cycles; €971 (€1858 vs €887). CONCLUSION: sc. administration is associated with lower administration costs. Switching patients from iv. to sc. would make it possible to treat more patients without increasing the personnel resources.

De-Escalation Strategies in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Early Breast Cancer (BC): Final Analysis of the West German Study Group Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early BC HER2- and Hormone Receptor-Positive Phase II Randomized Trial-Efficacy, Safety, and Predictive Markers for 12 Weeks of Neoadjuvant Trastuzumab Emtansine With or Without Endocrine Therapy (ET) Versus Trastuzumab Plus ET.

Purpose Human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive breast cancer is a distinct subgroup associated with lower chemotherapy sensitivity and slightly better outcome than HER2-positive/HR-negative disease. Little is known about the efficacy of the combination of endocrine therapy (ET) with trastuzumab or with the potent antibody-cytotoxic, anti-HER2 compound trastuzumab emtansine (T-DM1) with or without ET for this subgroup. The West German Study Group trial, ADAPT (Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer) compares pathologic complete response (pCR) rates of T-DM1 versus trastuzumab with ET in early HER2-positive/HR-positive breast cancer. Patients and Methods In this prospective, neoadjuvant, phase II trial, 375 patients with early breast cancer with HER2-positive and HR-positive status (n = 463 screened) were randomly assigned to 12 weeks of T-DM1 with or without ET or to trastuzumab with ET. The primary end point was pCR (ypT0/is/ypN0). Early response was assessed in 3-week post-therapeutic core biopsies (proliferation decrease ≥ 30% Ki-67 or cellularity response). Secondary end points included safety and predictive impact of early response on pCR. Adjuvant therapy followed national standards. Results Baseline characteristics were well balanced among the arms. More than 90% of patients completed the therapy per protocol. pCR was observed in 41.0% of patients treated with T-DM1, 41.5% of patients treated with T-DM1 and ET, and 15.1% with trastuzumab and ET ( P < .001). Early responders (67% of patients with assessable response) achieved pCR in 35.7% compared with 19.8% in nonresponders (odds ratio, 2.2; 95% CI, 1.24 to 4.19). T-DM1 was associated with a significantly higher prevalence of grade 1 to 2 toxicities, especially thrombocytopenia, nausea, and elevation of liver enzymes. Overall toxicity was low; seventeen therapy-related severe adverse events (T-DM1 arms v trastuzumab plus ET; 5.3% v 3.1%, respectively) were reported. Conclusion The ADAPT HER2-positive/HR-positive trial demonstrates that neoadjuvant T-DM1 (with or without ET) given for only 12 weeks results in a clinically meaningful pCR rate. Thus, a substantial number of patients are spared the adverse effects of systemic chemotherapy.

Cost drivers for breast, lung, and colorectal cancer care in a commercially insured population over a 6-month episode: an economic analysis from a health plan perspective.

AIMS: In the absence of clinical data, accurate identification of cost drivers is needed for economic comparison in an alternate payment model. From a health plan perspective using claims data in a commercial population, the objective was to identify and quantify the effects of cost drivers in economic models of breast, lung, and colorectal cancer costs over a 6-month episode following initial chemotherapy. RESEARCH DESIGN AND METHODS: This study analyzed claims data from 9,748 Cigna beneficiaries with diagnosis of breast, lung, and colorectal cancer following initial chemotherapy from January 1, 2014 to December 31, 2015. We used multivariable regression models to quantify the impact of key factors on cost during the initial 6-month cancer care episode. RESULTS: Metastasis, facility provider affiliation, episode risk group (ERG) risk score, and radiation were cost drivers for all three types of cancer (breast, lung, and colorectal). In addition, younger age (p < .0001) and human epidermal growth factor receptor-2 oncogene overexpression (HER2+)-directed therapy (p < .0001) were associated with higher costs in breast cancer. Younger age (p < .0001) and female gender (p < .0001) were also associated with higher costs in colorectal cancer. Metastasis was also associated with 50% more hospital admissions and increased hospital length of stay (p < .001) in all three cancers over the 6-month episode duration. Chemotherapy and supportive drug therapies accounted for the highest proportion (48%) of total medical costs among beneficiaries observed. CONCLUSIONS: Value-based reimbursement models in oncology should appropriately account for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, this study recommends adjusting for the factors identified in these models to predict costs in breast, lung, and colorectal cancers.

Cancer Care Coordinators to Improve Tamoxifen Persistence in Breast Cancer: How Heterogeneity in Baseline Prognosis Impacts on Cost-Effectiveness.

OBJECTIVES: To assess the cost-effectiveness of a cancer care coordinator (CCC) in helping women with estrogen receptor positive (ER+) early breast cancer persist with tamoxifen for 5 years. METHODS: We investigated the cost-effectiveness of a CCC across eight breast cancer subtypes, defined by progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, and local/regional spread. These subtypes range from excellent to poorer prognoses. The CCC helped in improving tamoxifen persistence by providing information, checking-in by phone, and "troubleshooting" concerns. We constructed a Markov macrosimulation model to estimate health gain (in quality-adjusted life-years or QALYs) and health system costs in New Zealand, compared with no CCC. Participants were modeled until death or till the age of 110 years. Some input parameters (e.g., the impact of a CCC on tamoxifen persistence) had sparse evidence. Therefore, we used estimates with generous uncertainty and conducted sensitivity analyses. RESULTS: The cost-effectiveness of a CCC for regional ER+/PR-/HER2+ breast cancer (worst prognosis) was NZ $23,400 (US $15,800) per QALY gained, compared with NZ $368,500 (US $248,800) for local ER+/PR+/HER2- breast cancer (best prognosis). Using a cost-effectiveness threshold of NZ $45,000 (US $30,400) per QALY, a CCC would be cost-effective only in the four subtypes with the worst prognoses. CONCLUSIONS: There is value in investigating cost-effectiveness by different subtypes within a disease. In this example of breast cancer, the poorer the prognosis, the greater the health gains from a CCC and the better the cost-effectiveness. Incorporating heterogeneity in a cost-utility analysis is important and can inform resource allocation decisions. It is also feasible to undertake in practice.

Cost-effectiveness and resource use of implementing MRI-guided NACT in ER-positive/HER2-negative breast cancers in The Netherlands.

BACKGROUND: Response-guided neoadjuvant chemotherapy (RG-NACT) with magnetic resonance imaging (MRI) is effective in treating oestrogen receptor positive/human epidermal growth factor receptor-2 negative (ER-positive/HER2-negative) breast cancer. We estimated the expected cost-effectiveness and resources required for its implementation compared to conventional-NACT. METHODS: A Markov model compared costs, quality-adjusted-life-years (QALYs) and costs/QALY of RG-NACT vs. conventional-NACT, from a hospital perspective over a 5-year time horizon. Health services required for and health outcomes of implementation were estimated via resource modelling analysis, considering a current (4 %) and a full (100 %) implementation scenario. RESULTS: RG-NACT was expected to be more effective and less costly than conventional NACT in both implementation scenarios, with 94 % (current) and 95 % (full) certainty, at a willingness to pay threshold of €20.000/QALY. Fully implementing RG-NACT in the Dutch target population of 6306 patients requires additional 5335 MRI examinations and an (absolute) increase in the number of MRI technologists, by 3.6 fte (full-time equivalent), and of breast radiologists, by 0.4 fte. On the other hand, it prevents 9 additional relapses, 143 cancer deaths, 23 congestive heart failure events and 2 myelodysplastic syndrome/acute myeloid leukaemia events. CONCLUSION: Considering cost-effectiveness, RG-NACT is expected to dominate conventional-NACT. While personnel capacity is likely to be sufficient for a full implementation scenario, MRI utilization needs to be intensified.

Disparities in Use of Human Epidermal Growth Hormone Receptor 2-Targeted Therapy for Early-Stage Breast Cancer.

PURPOSE: Trastuzumab is a key component of adjuvant therapy for stage I to III human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The rates and patterns of trastuzumab use have never been described in a population-based sample. The recent addition of HER2 information to the SEER-Medicare database offers an opportunity to examine patterns of trastuzumab use and to evaluate possible disparities in receipt of trastuzumab. METHODS: We examined a national cohort of Medicare beneficiaries with incident stage I to III HER2-positive breast cancer diagnosed in 2010 and 2011 (n = 1,362). We used insurance claims data to track any use of trastuzumab in the 12 months after diagnosis as well as to identify chemotherapy drugs used in partnership with trastuzumab. We used modified Poisson regression analysis to evaluate the independent effect of race on likelihood of receiving trastuzumab by controlling for clinical need, comorbidity, and community-level socioeconomic status. RESULTS: Overall, 50% of white women and 40% of black women received some trastuzumab therapy. Among women with stage III disease, 74% of whites and 56% of blacks received trastuzumab. After adjustment for tumor characteristics, poverty, and comorbidity, black women were 25% less likely to receive trastuzumab within 1 year of diagnosis than white women (risk ratio, 0.745; 95% CI, 0.60 to 0.93). CONCLUSION: Approxemately one half of patients 65 years of age and older with stage I to III breast cancer do not receive trastuzumab-based therapy, which includes many with locally advanced disease. Significant racial disparities exist in the receipt of this highly effective therapy. Further research that identifies barriers to use and increases uptake of trastuzumab could potentially improve recurrence and survival outcomes in this population, particularly among minority women.

A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada.

Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC. Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost-effectiveness of lapatinib plus letrozole compared with other widely used first-line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC. Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations. Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context.

Discordant assessment of tumor biomarkers by histopathological and molecular assays in the EORTC randomized controlled 10041/BIG 03-04 MINDACT trial breast cancer : Intratumoral heterogeneity and DCIS or normal tissue components are unlikely to be the cause of discordance.

Accurate identification of breast cancer patients most likely to benefit from adjuvant systemic therapies is crucial. Better understanding of differences between methods can lead to an improved ER, PgR, and HER-2 assessment. The purpose of this preplanned translational research is to investigate the correlation of central IHC/FISH assessments with microarray mRNA readouts of ER, PgR, and HER-2 status in the MINDACT trial and to determine if any discordance could be attributed to intratumoral heterogeneity or the DCIS and normal tissue components in the specimens. MINDACT is an international, prospective, randomized, phase III trial investigating the clinical utility of MammaPrint in selecting patients with early breast cancer for adjuvant chemotherapy (n = 6694 patients). Gene-expression data were obtained by TargetPrint; IHC and/or FISH were assessed centrally (n = 5788; 86 %). Macroscopic and microscopic evaluation of centrally submitted FFPE blocks identified 1427 cases for which the very same sample was submitted for gene-expression analysis. TargetPrint ER had a positive agreement of 98 %, and a negative agreement of 95 % with central pathology. Corresponding figures for PgR were 85 and 94 % and for HER-2 72 and 99 %. Agreement of mRNA versus central protein was not different when the same or a different portion of the tumor tissue was analyzed or when DCIS and/or normal tissue was included in the sample subjected to mRNA assays. This is the first large analysis to assess the discordance rate between protein and mRNA analysis of breast cancer markers, and to look into intratumoral heterogeneity, DCIS, or normal tissue components as a potential cause of discordance. The observed difference between mRNA and protein assessment for PgR and HER-2 needs further research; the present analysis does not support intratumoral heterogeneity or the DCIS and normal tissue components being likely causes of the discordance.

Cost-Effectiveness of Pertuzumab in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.

PURPOSE: The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) study showed a 15.7-month survival benefit with the addition of pertuzumab to docetaxel and trastuzumab (THP) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. We performed a cost-effectiveness analysis to assess the value of adding pertuzumab. PATIENT AND METHODS: We developed a decision-analytic Markov model to evaluate the cost effectiveness of docetaxel plus trastuzumab (TH) with or without pertuzumab in US patients with metastatic breast cancer. The model followed patients weekly over their remaining lifetimes. Health states included stable disease, progressing disease, hospice, and death. Transition probabilities were based on the CLEOPATRA study. Costs reflected the 2014 Medicare rates. Health state utilities were the same as those used in other recent cost-effectiveness studies of trastuzumab and pertuzumab. Outcomes included health benefits expressed as discounted quality-adjusted life-years (QALYs), costs in US dollars, and cost effectiveness expressed as an incremental cost-effectiveness ratio. One- and multiway deterministic and probabilistic sensitivity analyses explored the effects of specific assumptions. RESULTS: Modeled median survival was 39.4 months for TH and 56.9 months for THP. The addition of pertuzumab resulted in an additional 1.81 life-years gained, or 0.62 QALYs, at a cost of $472,668 per QALY gained. Deterministic sensitivity analysis showed that THP is unlikely to be cost effective even under the most favorable assumptions, and probabilistic sensitivity analysis predicted 0% chance of cost effectiveness at a willingness to pay of $100,000 per QALY gained. CONCLUSION: THP in patients with metastatic HER2-positive breast cancer is unlikely to be cost effective in the United States.

Assessment of Hormone Receptor and Human Epidermal Growth Factor Receptor 2 Status in Breast Carcinoma Using Thin-Prep Cytology Fine Needle Aspiration Cytology FISH Experience From China.

Estrogen receptor (ER) and progesterone receptor (PR) overexpression can be used to predict patient prognosis in breast cancer (BC). Human epidermal growth factor receptor 2 (HER2) is a reliable predictive marker in invasive breast cancer (IBC). Thin-Prep (TP) specimens are commonly utilized for immunocytochemistry (ICC) in fine needle aspiration cytology (FNAC). Thus, we sought to investigate if the incorporation of molecular diagnosis performed on TP-processed specimens is applicable in clinical practice. Hormone receptors (HRs) and HER2 immunocytochemistry was performed on 542 primary breast cancer FNAC specimens using the TP method. One hundred fourteen HER2 fluorescence in situ hybridization (FISH) analyses were performed on HER2 ICC 2+ FNAC specimens and the corresponding tissue samples. HRs results of TP slides and those of formalin-fixed paraffin-embedded (FFPE) slides were correlated well for ER (concordance rate =  3.3%, kappa value = 0.85) and PR (concordance rate = 88.6%, kappa value = 0.75). HER2 results for the TP slides and those of the matched FFPE slides also correlated well (concordance rate = 80.0%, kappa value = 0.62). The specificity of HER2 was 97.3%; however, the sensitivity was only 67.1%. Cytological specimens and histological samples showed a strong correlation (concordance rate = 99.1%, kappa value = 0.98) while being used to evaluate HER2 gene amplification. FNAC is a minimally invasive technique that can be used as an alternative method to collect tissue especially in cases where an excisional or core biopsy is difficult to obtain, or when recurrence is present. The results of ICC HRs in FNAC TP specimens may be used instead, but HER2 assessment may not be reliable enough for clinical use. FISH testing is necessary in this setting.

Modulatory effect of neoadjuvant chemotherapy on biomarkers expression; assessment by digital image analysis and relationship to residual cancer burden in patients with invasive breast cancer.

The use of digital imaging techniques for biomarker assessment has gained recognition as a valid tool for clinical use. In this study, we used image analysis for evaluation of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2), Ki-67 index, and p53 in 172 patients with invasive breast cancer treated with neoadjuvant chemotherapy and compared it with an untreated group (100 cases). We also examined the relationship between biomarker expression and the extent of residual disease using the Web-based MD Anderson residual cancer burden (RCB) calculator. Residual disease was classified as RCB 0/I, II, and III corresponding to complete/near-complete response, moderate, and extensive residual disease, respectively. Overall change in ER, PR, and HER2 status in the treated group was seen in 9.02% (P = .0148), 18.4% (P = .011), and 12.0% (P = .0042), respectively. Change in HER2 status, positive to negative and negative to positive, occurred in 27.2% and 7.0%, respectively. The group with RCB 0/I was frequently younger (P = .0057) and showed higher ER(-) status (P = .0316), lower ER scores (P = .0103), higher Ki-67 index (P = .0008), and p53 (P = .0055) compared with those with RCB II and III. Pathologic tumor stage (P = .0072), lumpectomy versus mastectomy (P = .0048), and p53 expression (P = .0190) were independent predictors of recurrence-free survival. The RCB categories (P = .0003) and tumor grade (P = .0049) were independent predictors of overall survival. This is the first study to conduct a comprehensive analysis of biomarkers in neoadjuvant chemotherapy-treated patients versus an untreated group using the digital image analysis method. We have demonstrated for the first time the relationship between RCB, tumor biomarkers expression, and clinical outcome.

Trastuzumab for the treatment of HER2-positive metastatic gastric cancer : a NICE single technology appraisal.

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of trastuzumab, Roche Pharmaceuticals, to submit evidence for the clinical and cost effectiveness of this drug for the treatment of advanced gastric cancer (aGC), as part of the Institute's single technology appraisal (STA) process. The Centre for Reviews and Dissemination (CRD) and the Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the evidence review group (ERG). This article provides a description of the company submission, the ERG report and NICE's subsequent decisions. In the initial appraisal by NICE, trastuzumab was rejected for use in the licensed population. Given this result, the manufacturer submitted additional evidence. In the final appraisal decision, trastuzumab was approved, in accordance with supplementary guidance issued by NICE on appraising life-extending, end-of-life treatments, for patients whose human epidermal growth factor receptor 2 (HER2) status was defined by an immunohistochemistry 3 positive (IHC3+) result. This appraisal highlights the need to fully assess the impact of different approaches to diagnostic testing on the cost effectiveness of targeted treatments. In this appraisal, it was found that the diagnostic strategy influenced the effectiveness and cost of trastuzumab. In the future, different diagnostic strategies should be compared in the incremental cost-effectiveness analysis.