High-value breast cancer care within resource limitations.

Breast cancer care is a costly global health issue where effective management depends on early detection and treatment. A breast cancer diagnosis can result in financial catastrophe especially in low- and middle-income countries (LMIC). Large inequities in breast cancer care are observed and represent a global challenge to caregivers and patients. Strategies to improve early diagnosis include awareness and clinical breast examination in LMIC, and screening in high-income countries (HIC). The use of clinical guidelines for the management of breast cancer is needed. Adapted guidelines from HIC can address disparities in populations with limited resources. Locally developed strategies still provide effective guidance in improving survival. Integrated practice units (IPU) with timely multidisciplinary breast care conferences and patient navigators are required to achieve high-value, personalized breast cancer management in HIC as well as LMIC. Breast cancer patient care should include a quality of life evaluation using ideally patient-reported outcomes (PROM) and experience measurements (PREM). Evaluation of breast cancer outcomes must include the financial cost of delivered care. The resulting value perspective should guide resource allocation and program priorities. The value of care must be improved by translating the findings of social and economic research into practice and resolving systemic inequity in clinical breast cancer research. Cancer survivorship programs must be put in place everywhere. The treatment of patients with metastatic breast cancer must require more attention in the future, especially in LMIC.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

PURPOSE: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer. METHODS: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases. "Surgery" group was defined by surgery of primary tumor up to nine months after diagnosis. We excluded women who did not receive systemic treatment or did not complete nine months follow-up after diagnosis. All the subsequent analyses reporting on overall survival and the stratified outcome analyses were performed based on this nine-month landmark cohort. OS was estimated using Kaplan-Meier method and compared using adjusted Cox proportional hazards models controlling for confounders with 95% confidence intervals (CI). We performed a stratified analysis according to surgery timing and a propensity score matching analysis. RESULTS: 1985 patients, 534 (26.9%) in the "Surgery" and 1451 (73.1%) in the "No Surgery" group. Patients undergoing surgery were younger (p < 0.001), had better performance status (PS) (p < 0.001), and higher proportion of HER2-positive and triple-negative breast cancer (p = 0.012). Median follow-up was 86.0 months (82.6-88.5). Median OS was 60.1 months (57.1-68.2) in the "Surgery" vs. 41.9 months (39.8-44.2) in the "No Surgery" group (adjusted HR 0.56; 0.49-0.64). OS was similar when surgery was performed upfront or after systemic treatment. Propensity score matching analysis confirmed the same findings. CONCLUSION: Among patients receiving systemic treatment for de novo metastatic breast cancer and surviving nine months or more, those who received surgery of the primary tumor within nine months of diagnosis have longer subsequent survival than those who did not.

Implementing and monitoring the right to health in breast cancer: selection of indicators using a Delphi process.

BACKGROUND: Women with breast cancer have different chances of surviving their disease, depending on where they live. Variations in survival may stem from unequal access to prompt diagnosis, treatment and care. Implementation of the right to health may help remedy such inequalities. The right to health is enshrined in international human rights law, notably Article 12 of the International Covenant on Economic, Social and Cultural Rights. A human rights-based approach to health requires a robust, just and efficient health system, with access to adequate health services and medicines on a non-discriminatory basis. However, it may prove challenging for health policymakers and cancer management specialists to implement and monitor this right in national health systems. METHOD: This article presents the results of a Delphi study designed to select indicators of implementation of the right to health to inform breast cancer care and management. In a systematic process, 13 experts examined an initial list of 151 indicators. RESULTS: After two rounds, 54 indicators were selected by consensus, three were rejected, three were added, and 97 remained open for debate. For breast cancer, right-to-health features selected as worth implementing and monitoring included the formal recognition of the right to health in breast cancer strategies; a population-based screening programme, prompt diagnosis, strong referral systems and limited waiting times; the provision of palliative, survivorship and end-of-life care; the availability, accessibility, acceptability and quality (AAAQ) of breast cancer services and medicines; the provision of a system of accountability; and the collection of anonymised individual data to target patterns of discrimination. CONCLUSION: We propose a set of indicators as a guide for health policy experts seeking to design national cancer plans that are based on a human rights-based approach to health, and for cancer specialists aiming to implement principles of the right to health in their practice. The 54 indicators selected may be used in High-Income Countries, or member states of the OECD who also have signed the International Covenant on Economic, Social and Cultural Rights to monitor progress towards implementation of the right to health for women with breast cancer.

Prospective non-interventional BELOVA/BGOG-ov16 study on safety of frontline bevacizumab in elderly patients with FIGO stage IV ovarian cancer: a study of the Belgian and Luxembourg Gynaecological Oncology Group.

OBJECTIVE: Because elderly patients with ovarian cancer are underrepresented in randomized studies, this study aimed to expand our knowledge on the safety and effectiveness of frontline treatment with bevacizumab in combination with standard carboplatin and paclitaxel chemotherapy in patients aged 70 years and older with a diagnosis of Federation of Gynecology and Obstetrics (FIGO) stage IV ovarian cancer in routine clinical practice in Belgium. METHODS: Patients aged 70 years and older with FIGO stage IV ovarian cancer were included in a multicenter, non-interventional prospective studyto evaluate the safety and effectiveness of treatment with bevacizumab in combination with frontline carboplatin and paclitaxel chemotherapy. Comprehensive geriatric assessments were performed at baseline and during treatment. RESULTS: The most frequently reported adverse events for bevacizumab were hypertension (55%), epistaxis (32%) and proteinuria (21%). The Kaplan-Meier estimate of progression-free survival was 14.5 months. The results of the comprehensive geriatric assessments during treatment indicated a slight improvement in the geriatric eight health status screening tool score for general health status and the mini-nutritional assessment score for nutritional status. The median change from baseline score was close to zero for the instruments measuring independency, activity of daily living and instrumental activities of daily living, and for the mobility-tiredness test measuring self-perceived fatigue. CONCLUSIONS: No new safety signals were registered in this study in patients aged 70 years and older treated with bevacizumab and frontline carboplatin and paclitaxel for FIGO stage IV ovarian cancer. Elderly patients should not be excluded from treatment for advanced ovarian cancer based on age alone. EU PAS REGISTER: ENCEPP/SDPP/13849. CLINICALTRIALSGOV IDENTIFIER: NCT02393898.

Phase II study of weekly paclitaxel/carboplatin in combination with prophylactic G-CSF in the treatment of gynecologic cancers: A study in 108 patients by the Belgian Gynaecological Oncology Group.

OBJECTIVE: To investigate the addition of prophylactic G-CSF to each weekly paclitaxel/carboplatin course in patients with recurrent platinum-resistant ovarian (OC), or recurrent or advanced endometrial (EC) or cervical carcinoma (CC). METHODS: 108 patients were enrolled i.e. 36 in each cohort. Eighteen courses of paclitaxel (60 mg/m(2)) and carboplatin (AUC 2.7) were administered weekly. G-CSF (filgrastim) was given to all patients on day 5 (and if needed on day 6). RESULTS: For patients with OC, 91% had platinum-resistant and 9% platinum-refractory disease. Median number of prior chemotherapy lines was 3 for OC, 1 for EC, and 1 for CC. Grade 3-4 neutropenia was observed in 34% of patients (95% CI: 26%-44%, P<0,0001) (OC 29%, EC 36%, CC 38%). This is lower compared to historical data in all cohorts (84%). Confirmed sepsis was observed in 5%, grade 3-4 thrombocytopenia in 41%, grade 2-3 peripheral neuropathy in 17% of patients. In 71% of patients dose was delayed. Dose reduction was necessary for carboplatin in 47% and paclitaxel in 18% of patients. ORR was 51% (OC 48%, EC 45%, CC 58%). Median (95% CI) PFS and OS was 7.1 (5.1-8.1) and 12.7 (10.2-16.3) months, respectively (OC 7 and 13, EC 6 and 19, CC 6 and 14). CONCLUSION: Weekly paclitaxel/carboplatin with G-CSF is an effective treatment with acceptable toxicity in patients with platinum-resistant or platinum-refractory OC, advanced or recurrent EC and CC. The incidence of grade 3-4 neutropenia is lower with the addition of weekly G-CSF compared with earlier studies without routine use of prophylactic G-CSF.

Comparing duration of response and duration of clinical benefit between fulvestrant treatment groups in the CONFIRM trial: application of new methodology.

Comparisons of duration of response (DoR) and duration of clinical benefit (DoCB) within clinical trials are prone to biases. To address these biases, we used new methodology to prospectively analyze expected DoR and expected DoCB. Objective response rate and clinical benefit rate were calculated for fulvestrant 500 and 250 mg, and used to calculate expected DoR and expected DoCB for each dose group. The ratios for expected DoR and expected DoCB (expected DoR500/expected DoR250 and expected DoCB500/expected DoCB250) were then calculated, thereby allowing statistical comparisons of these endpoints between each arm of the COmparisoN of Faslodex In Recurrent or Metastatic breast cancer (CONFIRM) trial. Expected DoRs for fulvestrant 500 and 250 mg were 3.2 and 3.6 months, respectively. The expected DoR ratio between fulvestrant 500 and 250 mg was not statistically significant (0.89; 95 % CI, 0.48-1.67, P = 0.724). The expected DoCBs for fulvestrant 500 and 250 mg were 9.8 and 7.2 months, respectively. The expected DoCB ratio showed that the expected DoCB for fulvestrant 500 mg was significantly improved compared with the expected DoCB for fulvestrant 250 mg (1.36; 95 % CI, 1.07-1.73, P = 0.013). Analysis of the expected DoR and expected DoCB showed fulvestrant 500 mg significantly increased expected DoCB compared with fulvestrant 250 mg in the CONFIRM trial.

Trends and variation in treatment of early breast cancer in European certified breast centres: an EUSOMA-based analysis.

BACKGROUND: Practice indicators (PI) measure provided care making use of real-world data. This study describes trends and variations in adjuvant treatment of early breast cancer (EBC) using the European Society of Breast Cancer Specialists (EUSOMA) database. METHODS: The analysis was conducted on anonymous cumulative data registered by 56 certified breast centres, which all entered at least 500 new diagnoses in the database in the 10-year period 2010-2019. Practice trends of radiotherapy, endocrine treatment, chemotherapy, and anti-HER2 therapy were evaluated. The association with age group (<50, 50-69, ≥70) and geographical area of the centre (Northern, Central, Southern Europe; NE, CE, SE) was assessed with the Pearson Chi2 test for independence in contingency tables. RESULTS: In total, 150,150 patients with EBC were selected. Overall, radiotherapy was administered more frequently in NE centres, and conversely, endocrine, chemo-, and anti-HER2 therapy were used more frequently in SE centres (p<0.001). 46.9% of the pN1 patients received postmastectomy radiotherapy, with significant differences by age and geographical region (p < 0.001). Adjuvant endocrine treatment for endocrine-sensitive carcinoma in situ was administered in 46.1%, with a decreasing trend during the study period (58.5-34.5%; p < 0.001). Anti-HER2 therapy was delivered in 75.6% of all patients with HER2BC T1a/bN0, patients older than 70 received anti-HER2 in 67.6% in SE compared to 31.3% in NE centres. CONCLUSION: Important variations in EBC management between European certified breast centres have been demonstrated. PI using real-world data can help to monitor, evaluate, and eventually guide and align good clinical practice in the management of breast cancer.

High-grade serous cancer of undetermined primary origin presenting as solitary inguinal lymph node enlargement.

A 62-year-old woman presented with unilateral inguinal lymphadenopathy, existing for several months. As it was initially thought to be lymphoma, the lymph node was resected. Pathology, however, revealed a metastasis of a high-grade papillary serous cancer, according to its stainings, most likely ovarian in origin. Further staging showed lymphadenopathies in the inguinofemoral, para-aortic and mediastinal regions. Consequently, the multidisciplinary oncologic meeting advised a diagnostic laparoscopy which showed no macroscopic spread within the abdomen. Pathological examination of biopsies as well as both ovaries showed no sign of ovarian cancer. The patient received standard chemotherapy, that is, carbo-Taxol-Avastin, to which she showed complete response after three cycles as shown on positron emission tomography-CT. A review of existing literature showed that this is a very unusual case of high-grade serous carcinoma, where no site of origin could be found.

New Frontiers for Fairer Breast Cancer Care in a Globalized World.

In early 2020, the book "Breast cancer: Global Quality Care" was published by Oxford University Press. In the year since then, publications, interviews (by ecancer), presentations, webinars, and virtual congress have been organized to disseminate further the main message of the project: "A call for Fairer Breast Cancer Care for all Women in a Globalized World." Special attention is paid to increasing the "value-based healthcare" putting the patient in the center of the care pathway and sharing information on high-quality integrated breast cancer care. Specific recommendations are made considering the local resource facilities. The multidisciplinary breast conference is considered "the jewel in the crown" of the integrated practice unit, connecting multiple specializations and functions concerned with patients with breast cancer. Management and coordination of medical expertise, facilities, and their interfaces are highly recommended. The participation of two world-leading cancer research programs, the CONCORD program and Breast Health Global Initiative, in this project has been particularly important. The project is continuously under review with feedback from the faculty. The future plan is to arrive at an openaccess publication that is freely available to all interested people. This project is designed to help ease the burden and suffering of women with breast cancer across the globe.

Myelopreservation with Trilaciclib in Patients Receiving Topotecan for Small Cell Lung Cancer: Results from a Randomized, Double-Blind, Placebo-Controlled Phase II Study.

INTRODUCTION: Multilineage myelosuppression is an acute toxicity of cytotoxic chemotherapy, resulting in serious complications and dose modifications. Current therapies are lineage specific and administered after chemotherapy damage has occurred. Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor that is administered prior to chemotherapy to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation). METHODS: In this randomized, double-blind, placebo-controlled phase II trial, patients with previously treated extensive-stage small cell lung cancer (ES-SCLC) were randomized to receive intravenous trilaciclib 240 mg/m2 or placebo before topotecan 1.5 mg/m2 on days 1-5 of each 21-day cycle. Primary endpoints were duration of severe neutropenia (DSN) in cycle 1 and occurrence of severe neutropenia (SN). Additional endpoints were prespecified to further assess the effect of trilaciclib on myelopreservation, safety, patient-reported outcomes (PROs), and antitumor efficacy. RESULTS: Thirty-two patients received trilaciclib, and 29 patients received placebo. Compared with placebo, administration of trilaciclib prior to topotecan resulted in statistically significant and clinically meaningful decreases in DSN in cycle 1 (mean [standard deviation] 2 [3.9] versus 7 [6.2] days; adjusted one-sided P < 0.0001) and occurrence of SN (40.6% versus 75.9%; adjusted one-sided P = 0.016), with numerical improvements in additional neutrophil, red blood cell, and platelet measures. Patients receiving trilaciclib had fewer grade ≥ 3 hematologic adverse events than patients receiving placebo, particularly neutropenia (75.0% versus 85.7%) and anemia (28.1% versus 60.7%). Myelopreservation benefits extended to improvements in PROs, specifically in those related to fatigue. Antitumor efficacy was comparable between treatment arms. CONCLUSIONS: Compared with placebo, the addition of trilaciclib prior to topotecan for the treatment of patients with previously treated ES-SCLC improves the patient experience of receiving chemotherapy, as demonstrated by a reduction in chemotherapy-induced myelosuppression, improved safety profile, improved quality of life and no detrimental effects on antitumor efficacy. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02514447.

The use of chemotherapy regimens carrying a moderate or high risk of febrile neutropenia and the corresponding management of febrile neutropenia: an expert survey in breast cancer and non-Hodgkin's lymphoma.

BACKGROUND: The use of chemotherapy regimens with moderate or high risk of febrile neutropenia (defined as having a FN incidence of 10% or more) and the respective incidence and clinical management of FN in breast cancer and NHL has not been studied in Belgium. The existence of a medical need for G-CSF primary and secondary prophylaxis with these regimens was investigated in a real-life setting. METHODS: Nine oncologists and six hematologists from different Belgian general hospitals and university centers were surveyed to collect expert opinion and real-life data (year 2007) on the use of chemotherapy regimens with moderate or high risk of febrile neutropenia and the clinical management of FN in patients aged <65 years with breast cancer or NHL. Data were retrospectively obtained, over a 6-month observation period. RESULTS: The most frequently used regimens in breast cancer patients (n = 161) were FEC (45%), FEC-T (37%) and docetaxel alone (6%). In NHL patients (n = 39), R-CHOP-21 (33%) and R-ACVBP-14 (15%) were mainly used. Without G-CSF primary prophylaxis (PP), FN occurred in 31% of breast cancer patients, and 13% had PSN. After G-CSF secondary prophylaxis (SP), 4% experienced further FN events. Only 1 breast cancer patient received PP, and did not experience a severe neutropenic event. Overall, 30% of chemotherapy cycles observed in breast cancer patients were protected by PP/SP. In 10 NHL patients receiving PP, 2 (20%) developed FN, whereas 13 (45%) of the 29 patients without PP developed FN and 3 (10%) PSN. Overall, 55% of chemotherapy cycles observed in NHL patients were protected by PP/SP. Impaired chemotherapy delivery (timing and/or dose) was reported in 40% (breast cancer) and 38% (NHL) of patients developing FN. Based on oncologist expert opinion, hospitalization rates for FN (average length of stay) without and with PP were, respectively, 48% (4.2 days) and 19% (1.5 days). Similar rates were obtained from hematologists. CONCLUSIONS: Despite the studied chemotherapy regimens being known to be associated with a moderate or high risk of FN, upfront G-CSF prophylaxis was rarely used. The observed incidence of severe neutropenic events without G-CSF prophylaxis was higher than generally reported in the literature. The impact on medical resources used is sizeable.

Breast Cancer: global quality care optimizing care delivery with existing financial and personnel resources.

Our vision about breast cancer quality care within a global health framework was recently published by Oxford University Press. The aim of our work was to reflect on the potential to achieve a world-wide improvement in quality care, assessing value for money. The population-based survival estimates from the CONCORD programme and the Breast Health Global Initiative (BHGI) are valuable tools for this global effort. Because cancer care delivery is becoming unsustainable in many countries assessing healthcare value for the cost is becoming increasingly important. Recommendations are made for better global quality care for patients with breast cancer.

Neutropenia management in patients receiving myelosuppressive polychemotherapy for early breast cancer in Belgium: BRONS study results.

Background: Chemotherapy plays an important role in the treatment of early breast cancer (EBC). Granulocyte-colony stimulating factors (G-CSF) can reduce the risk of febrile neutropenia as primary prophylaxis (PP) or secondary prophylaxis (SP). The BRONS study investigated the incidence of serious neutropenic events (SNE) and G-CSF use in a Belgian population of EBC patients treated with myelosuppressive polychemotherapy.Methods: Conducted in 2011, this study was a prospective, multicentre, observational trial involving 260 patients. The primary endpoint was the incidence of SNE defined as either febrile neutropenia (FN) or prolonged severe neutropenia (PSN; neutrophil count ≤0.5 × 109 for at least five days). Secondary endpoints included a description of the chemotherapeutic regimens prescribed and G-CSF use.Results: Nine percent of patients were treated with a dose-dense regimen (DD) and 91% received classical chemotherapy (CC). PP with G-CSF (PPG) was given to 20% of patients (100% in DD and 11% in CC). Eighteen percent of patients presented a SNE (4% in DD and 20% in CC) of which 15% were FN and 3% PSN. SNE occurrence was 8% in the PPG subgroup and 21% in the no-PPG subgroup. In the DD subgroup, all patients received PPG and no FN was reported. Twenty six adverse events related to G-CSF were reported in 8.2% of patients and two of these were classified as severe.Conclusion: This observational study highlights the high incidence of SNE with CC regimens in patients who do not receive PPG. It also confirms the safe profile of DD regimens with G-CSF support.

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study.

OBJECTIVES: The double-blind, phase III CONFIRM study (NCT00099437) evaluated fulvestrant 500 mg vs fulvestrant 250 mg in postmenopausal women with hormone receptor-positive locally advanced/metastatic breast cancer (LA/MBC). This post-hoc analysis investigated the efficacy and safety of fulvestrant given either first-line or second-line for advanced disease. MATERIALS & METHODS: Progression-free survival (PFS) and overall survival (OS) with fulvestrant 500 mg vs fulvestrant 250 mg was evaluated using unadjusted log-rank tests in patients treated in the first- (progression during or within 12 months after completing adjuvant endocrine therapy; n = 387) and second-line (following endocrine therapy for LA/MBC; n = 343) settings. RESULTS: First-line fulvestrant 500 mg significantly prolonged PFS vs fulvestrant 250 mg (median PFS 5.6 vs 4.2 months; hazard ratio [HR] 0.80; 95% confidence interval [CI] 0.64-1.00; p = .047). Median PFS was numerically greater with second-line fulvestrant 500 mg vs fulvestrant 250 mg (7.9 vs 6.3 months; HR 0.80; 95% CI 0.64-1.02; p = .068). At data cut-off (75.5% maturity), median OS with first-line fulvestrant 500 mg was 23.2 vs 22.1 months with fulvestrant 250 mg (HR 0.87; 95% CI 0.70-1.10; p = .251), and 29.2 vs 22.8 months, respectively, in the second-line (HR 0.75; 95% CI 0.58-0.96; p = .020). The safety profile was broadly comparable between dose groups and across treatment lines, and consistent with the overall patient population. CONCLUSION: The superiority of fulvestrant 500 mg over fulvestrant 250 mg in patients with LA/MBC in CONFIRM was consistent in both the first- and second-line settings for PFS, and numerically greater in both settings for OS.

Managing cancer care through service delivery networks: The role of professional collaboration in two European cancer networks.

Background The study examines two meso-strategic cancer networks, exploring to what extent collaboration can strengthen or hamper network effectiveness. Unlike macro-strategic networks, meso-strategic networks have no hierarchical governance structures nor are they institutionalised within healthcare services' delivery systems. This study aims to analyse the models of professional cooperation and the tools developed for managing clinical practice within two meso-strategic, European cancer networks. Methods Multiple case study design based on the comparative analysis of two cancer networks: Iridium, in Antwerp, Belgium and the Institut Català d'Oncologia in Catalonia, Spain. The case studies applied mixed methods, with qualitative research based on semi-structured interviews ( n = 35) together with case-site observation and material collection. Results The analysis identified four levels of collaborative intensity within medical specialties as well as in multidisciplinary settings, which became both platforms for crosscutting clinical work between hubs' experts and local care teams and the levers for network-based tools development. The organisation of clinical practice relied on professional-based cooperative processes and tiers, lacking vertical integration mechanisms. Conclusions The intensity of professional linkages largely shaped the potential of meso-strategic cancer networks to influence clinical practice organisation. Conversely, the introduction of managerial techniques or network governance structures, without introducing vertical hierarchies, was found to be critical solutions.

UCBG 2-08: 5-year efficacy results from the UNICANCER-PACS08 randomised phase III trial of adjuvant treatment with FEC100 and then either docetaxel or ixabepilone in patients with early-stage, poor prognosis breast cancer.

PURPOSE: UNICANCER-PACS08 compared adjuvant FEC (5-FU; epirubicin; cyclophosphamide) then docetaxel to FEC then ixabepilone in poor prognosis early breast cancer (BC). We evaluated whether replacing docetaxel with ixabepilone would increase 5-year disease-free survival (DFS). PATIENTS AND METHODS: Triple-negative breast cancer (TNBC) or oestrogen receptor (ER)+/progesterone receptor (PR)-/HER2- BC patients were randomised to receive standard FEC (3 cycles) followed by 3 cycles of either docetaxel (100 mg/m2) or ixabepilone (40 mg/m2). Radiotherapy was mandatory after conservative surgery; ER+ patients received endocrine therapy. RESULTS: Seven hundred sixty-two patients were enrolled between October 2007 and September 2010. Baseline characteristics were balanced between arms. Median follow-up was 66.7 months. Median DFS was not reached; 5-year DFS rate was 76% with docetaxel and 79% with ixabepilone (hazard ratio [HR] = 0.80; 95% confidence interval [CI] = 0.58-1.10; p = 0.175). Median overall survival (OS) was not reached; 5-year OS rate was 86% versus 84% (HR = 0.97; 95% CI = 0.66-1.42; p = 0.897). TNBC patients treated with ixabepilone had a 23% lower risk of relapse compared to docetaxel (HR for DFS = 0.77; 95% CI = 0.53-1.11; p = 0.168). DFS was longer with ixabepilone than docetaxel in patients with grade II-III lymphocytic infiltration (HR = 0.55; 95% CI = 0.29-1.05; p = 0.063). All patients experienced ≥1 adverse events (AEs): 75% reported grade III-IV AEs and two (<1%) had grade V AEs (both with neutropenia and infection receiving ixabepilone). CONCLUSION: After adjuvant FEC, ixabepilone was comparable to docetaxel for treating poor prognosis early BC patients. The benefit of ixabepilone in subgroups (patients with TNBC and grade II-III lymphocytic infiltration) requires further evaluation.

Tamoxifen Metabolism and Efficacy in Breast Cancer: A Prospective Multicenter Trial.

Purpose: Levels of endoxifen, the most active metabolite of tamoxifen, vary by the highly polymorphic cytochrome P450 (CYP) 2D6 enzyme. We prospectively investigated tamoxifen efficacy by serum endoxifen levels and the tamoxifen activity score (TAS).Experimental Design: A prospective observational multicenter study included postmenopausal women with an estrogen receptor-positive breast cancer receiving first-line tamoxifen, 20 mg daily in the neoadjuvant or metastatic setting, recruited between February 2009 and May 2014. The primary endpoint was the objective response rate (ORR) using RECIST criteria 1.0. Secondary endpoints were clinical benefit (CB), progression-free survival (PFS), and tolerability of tamoxifen. The main analysis used logistic regression to relate ORR to serum endoxifen levels after 3 months. Endpoints were also related to other tamoxifen metabolites and to TAS.Results: Endoxifen levels were available for 247 of all 297 patients (83%), of which 209 with target lesions (85%). Median follow-up time for PFS was 32.5 months, and 62% progressed. ORR and CB were 45% and 84%, respectively. ORR was not related to endoxifen, and the OR of ORR was 1.008 per µg/L increase in endoxifen (95% confidence interval, 0.971-1.046; P = 0.56). In general, none of the endpoints was associated with endoxifen levels, tamoxifen metabolites, or TAS.Conclusions: Under the prespecified assumptions, the results from this prospective clinical trial do not suggest therapeutic drug monitoring of endoxifen to be of clinical value in postmenopausal women treated with tamoxifen for breast cancer in the neoadjuvant or metastatic setting. Clin Cancer Res; 24(10); 2312-8. ©2018 AACR.

Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial.

BACKGROUND: At the time of the initial analysis of overall survival (OS) for the Comparison of Faslodex in Recurrent or Metastatic Breast Cancer (CONFIRM) randomized, double-blind, phase III trial, approximately 50% of patients had died. A final analysis of OS was subsequently planned for when 75% of patients had died. METHODS: Patients were randomly assigned 1:1 to fulvestrant 500 mg administered as two 5-mL intramuscular injections on days 0, 14, and 28 and every 28 (±3) days thereafter or fulvestrant 250 mg administered as two 5-mL intramuscular injections (one fulvestrant and one placebo [identical in appearance to study drug]) on days 0, 14 (two placebo injections only), and 28 and every 28 (±3) days thereafter. OS was analyzed using an unadjusted log-rank test. No adjustments were made for multiplicity. Serious adverse events (SAEs) and best response to subsequent therapy were also reported. All statistical tests were two-sided. RESULTS: In total, 736 women (median age = 61.0 years) were randomly assigned to fulvestrant 500 mg (n = 362) or 250 mg (n = 374). At the final survival analysis, 554 of 736 (75.3%) patients had died. Median OS was 26.4 months for fulvestrant 500 mg and 22.3 months for 250 mg (hazard ratio = 0.81; 95% confidence interval = 0.69-0.96; nominal P = .02). There were no clinically important differences in SAE profiles between the treatment groups; no clustering of SAEs could be detected in either treatment group. Type of first subsequent therapy and objective responses to first subsequent therapy were well balanced between the two treatment groups. CONCLUSIONS: In patients with locally advanced or metastatic estrogen receptor-positive breast cancer, fulvestrant 500 mg is associated with a 19% reduction in risk of death and a 4.1-month difference in median OS compared with fulvestrant 250 mg. Fulvestrant 500 mg was well tolerated, and no new safety concerns were identified.