Schizophrenia does not adversely affect the treatment of women with breast cancer: A cohort study

BackgroundData on the natural course of patients with breast cancer and schizophrenia are limited. Although there have been studies in assessing the incidence of breast cancer in the setting of schizophrenia, there is very little information concerning the clinical profile of these women.MethodsWe analyzed the data from our electronic notes system by searching for the terms ‘schizophrenia’ or ‘schizophrenic’ and ‘breast cancer’ or ‘tumour’ between 1993 and 2009. Information was collected on demographics, clinico-pathologic disease variables, treatment including anti-emetic use, chemotherapy delivery and outcomes.ResultsFrom 90,676 patients screened, we identified 37 individuals who had breast cancer and a pre-existing underlying diagnosis of schizophrenia. Of these, 30 (81%) presented with early breast cancer and 7 (19%) presented with metastatic disease. Node positivity was observed in 14 individuals (38%). The average interval between diagnosis of schizophrenia and breast cancer was more than 20 years in the majority of the patients. Treatment outcomes, trial involvement, compliance and ability to provide informed consent were similar to our previously published cohort data.ConclusionsSchizophrenia does not affect treatment delivery or outcomes in women with breast cancer. The presence of schizophrenia should not be a limiting factor for entry into clinical trials. Breast cancer patients with this illness should be offered standard treatment without discrimination, including entry into clinical trials.     

Treatment of Luminal Metastatic Breast Cancer beyond CDK4/6 Inhibition: Is There a Standard of Care in Clinical Practice?

BackgroundCDK4/6 inhibitors have become the standard for first-line treatment of metastatic luminal breast cancer based on consistent data from several phase 3 trials demonstrating clinically meaningful improvement of progression-free as well as overall survival. In addition, they are about to become a part of adjuvant treatment for patients with high-risk luminal disease based on positive results from the first randomized phase 3 trial on abemaciclib. Nevertheless, the majority of patients with advanced or metastatic luminal breast cancer and prospectively a relevant proportion of patients treated in the adjuvant setting will eventually develop resistance to this endocrine based combination within 12–36 months, depending on the line of treatment.ConclusionPotential subsequent therapies include PI3K inhibitors, mTOR inhibitors, endocrine monotherapy, PARP inhibitors, and chemotherapy. However, these therapies have mainly been developed in the pre-CDK4/6 inhibitor era and little is known about potential cross-resistance. The concept of continuing CDK4/6 inhibition beyond progression is supported by some preclinical data, but to date there is very limited clinical evidence to support this strategy. Therefore, treatment of metastatic luminal breast cancer after progression on CDK4/6 inhibitors remains a challenge.Key MessagesHere we review current evidence from pro- and retrospective studies and give an outlook on future developments with respect to novel therapeutic agents, including oral SERD and AKT inhibitors, which have the potential to change the therapeutic landscape in the future. Furthermore, clinical treatment algorithms and current research will also be discussed.     

Eligibility of real-world patients with metastatic breast cancer for clinical trials

IntroductionThe results of clinical trials in metastatic breast cancer (MBC) are generalized to real-world patients. This study determines the proportion of real-world patients who would be eligible for clinical trials and compares outcomes in eligible versus ineligible patients.MethodsPatients diagnosed with MBC from 2004 to 2015 in a large Canadian province were included. Patients with one of the following criteria were considered ineligible: the presence of comorbid conditions (anemia, uncontrolled diabetes, heart disease, liver disease, and kidney disease) or a history of immunosuppression or prior malignancy. The likelihood of receiving cancer therapy was analysed using logistic regression models and factors affecting overall survival (OS) were assessed by Cox proportional hazards models.ResultsA total of 1585 patients with MBC were identified. The median age at diagnosis was 63 years. Of these, 512 (32.3%) patients were deemed ineligible in whom the two most common reasons for ineligibility were renal dysfunction (17.2%), and previous immunosuppression (7.8%). In the real world, ineligible patients were less likely to receive chemotherapy (29.5% vs 45.8%; P < 0.001) but not radiation treatment (7.6% vs 9.6%; P = 0.196) or hormonal therapy (57.6% vs 60.6%; P = 0.261). The 5-year OS of ineligible patients who received systemic therapy in the real-world was significantly better than those who did not.ConclusionsDespite being ineligible for clinical trials based on common eligibility criteria, many real-world patients receive systemic treatment and derive possible benefit. Broadening of inclusion criteria in clinical trials will enhance the representation of real-world patients and increase the generalizability of results.     

Dual HER2 blockade in the first-line treatment of metastatic breast cancer - A retrospective population-based observational study in Danish patients

ObjectivesRandomized clinical trials do not include a population that truly reflects a real-world population, due to their inclusion and exclusion criteria. This leads to concerns about the applicability of these studies in a clinical practice. In the present study, we aim to describe the clinical and demographic characteristics, treatment patterns, and clinical outcomes in a population of patients with HER2-positive metastatic breast cancer who received pertuzumab and trastuzumab as first-line treatment in a real-world setting.MethodsThe database of the Danish Breast Cancer Group was used to assemble data on patients included in the period April 2013 to August 2017. The primary endpoints were overall survival (OS) and progression-free survival (PFS).ResultsA cohort of 291 patients with a median age of 58 years was registered. Hereof 112 (38%) patients with de novo disease (primary disseminated) and 179 (62%) with recurrence. The median follow-up for OS was 24.1 months. The median OS was 41.8 months (95% CI, 37.7 to NE) and the median PFS was 15.8 months (95% CI, 14.0 to 19.9). For de novo patients alone, the median OS was not reached whereas the median PFS was 17.9 months (95% CI, 14.3 to 27.3).Hazard ratios for patients receiving vinorelbine showed comparable results as for the whole population.ConclusionThis heterogeneous patient population in a real-world setting had a PFS comparable with what could be expected from the related randomized trial. The de novo patients had better OS and PFS as compared to patients with recurrence.     

Sentinel node biopsy in early breast cancer. A review on recent and ongoing randomized trials

IntroductionSentinel Lymph Node Biopsy (SLNB) is regarded as the standard procedure for nodal staging in patients with early breast cancer. In the last decade several randomized trials have been evaluating its role and indications.Materials and methodsThis article reviews recent and ongoing randomized trials on SLNB.ResultsFour randomized controlled trials have recently shown evidence that SLNB either alone or followed by radiation therapy is effective for the management in patients with low axillary tumor burden in early breast cancer. Nine randomized controlled trials on SLNB are ongoing: four assessing its role in case of positive sentinel node, three evaluating whether SLNB itself can be omitted when the preoperative nodal imaging is negative, two are studying SLNB in the neoadjuvant setting.Discussion and conclusionSLNB either alone or with axillary radiotherapy has been shown to be non-inferior to complete axillary dissection in terms of local recurrence, disease-free survival and overall survival in early breast cancer with minimally metastatic axilla. So far, results from ongoing trials are going to confirm the appropriate treatment in patients with limited axillary nodal involvement, the role and the timing of SLNB within the neoadjuvant setting and to define whether surgery can be avoided in the axilla in early stage breast cancer patients with negative preoperative imaging.     

Real-world use of systemic therapies in men with metastatic castration resistant prostate cancer (mCRPC) in Canada

BackgroundManagement of advanced prostate cancer has evolved rapidly with the availability of multiple systemic treatments such as androgen-receptor axis-targeted therapies (ARATs), taxane-based chemotherapy, radium-223, and other approaches. However, limited data exists on real-world treatment selection and clinical outcomes. This study examines the utilization and survival impact of these therapies in men with metastatic castration-resistant prostate cancer (mCRPC) in the real-world setting of Ontario, Canada.MethodsThis study was a retrospective, longitudinal, population-based study of administrative claims data between January 2016 and April 2020. Men ≥ 66 years with mCRPC receiving advanced treatment were included. Patients were indexed on the day they initiated mCRPC treatment and followed up until death or end of study period to assess treatment and survival. Multinomial regression was used to model the association between baseline covariates, treatment and survival.ResultsMedian age was 75 years among the 944 mCRPC patients who received life-prolonging therapies during this time period. Over 90% of patients used an ARAT as a first-line therapy, and 71.5% received only first-line therapy before death or censoring. Of patients that received two or more lines, over 80% received subsequent therapy with a different mechanism of action. Median overall survival was 18.9 months.ConclusionsARATs have become the predominant first-line systemic treatment option for mCRPC patients in recent years. Notably, the majority of patients received only a single line of life-prolonging therapy after developing mCRPC. In keeping with the recognized efficacy-effectiveness gap, real-world outcomes in this cohort appear poorer than in clinical trials.     

Increasing minority patient participation in cancer clinical trials using oncology nurse navigation

BackgroundResidential distance from an academic or cancer center is a significant barrier to minority patient participation in cancer research. Most cancer clinical trials (CTs) are only accessible at academic and cancer centers, yet most cancer patients receive treatment in their home communities where access to CTs may be limited. Oncology nurse navigation is an innovative approach for increasing minority CT participation by facilitating access to cancer CTs in communities where minority patients live. The purpose of this study was to evaluate the impact of oncology nurse navigation on community-based recruitment of black patients to breast cancer CTs at a major cancer center.MethodsWe merged the roles of a traditional oncology research nurse and a professional patient navigator to create a novel health care provider role, the oncology nurse navigator. The primary duties of the oncology nurse navigator were to engage black cancer patients in the offices of their community physicians and to collaborate with community physicians to increase black patient participation in cancer research. The oncology nurse navigator played a key role in all phases of the CT participation process (e.g., screening for eligibility and completion of informed consent and clinical research forms) and guided each patient around barriers in the health care system. The accrual of eligible patients to breast cancer CTs was used to assess the impact of oncology nurse navigation on community-based recruitment of blacks to cancer CTs.ResultsBetween January 2007 and December 2008, a total of 132 black breast cancer patients were screened by a single oncology nurse navigator for eligibility to University of Southern California–sponsored breast cancer CTs. Fifty-nine patients were eligible for CTs, and each was invited to participate in 1 or more CTs for which they were eligible. Fifty-one of 59 eligible black patients (86% of eligible patients) were enrolled to 1 or more research protocols. The estimated cost per enrolled patient was $5,677, nearly half the expected per patient cost of treating patients on CT at an academic or cancer center.ConclusionsOncology nurse navigation is an effective outreach strategy for increasing black patient participation in cancer research and may be achieved at nearly half the cost of traditional methods of enrolling patients in CTs at cancer centers.     

Progression-free survival and quality of life in metastatic breast cancer: The patient perspective

IntroductionTreatment advances for metastatic breast cancer (mBC) have improved overall survival (OS) in some mBC subtypes; however, there remains no cure for mBC. Considering the use of progression-free survival (PFS) and other surrogate endpoints in clinical trials, we must understand patient perspectives on measures used to assess treatment efficacy.ObjectiveTo explore global patient perceptions of the concept of PFS and its potential relation to quality of life (QoL).Materials and methodsVirtual roundtables in Europe and the United States and interviews in Japan with breast cancer patients, patient advocates, and thought leaders. Discussions were recorded, transcribed, and analyzed thematically.ResultsLengthened OS combined with no worsening or improvement in QoL remain the most important endpoints for mBC patients. Time when the disease is not progressing is meaningful to patients when coupled with improvements in QoL and no added treatment toxicity. Clinical terminology such as “PFS” is not well understood, and participants underscored the need for patient-friendly terminology to better illustrate the concept. Facets of care that patients with mBC value and that may be related to PFS include relief from cancer-related symptoms and treatment-related toxicities as well as the ability to pursue personal goals. Improved communication between patients and providers on managing treatment-related toxicities and addressing psychosocial challenges to maintain desired QoL is needed.ConclusionWhile OS and QoL are considered the most relevant endpoints, patients also value periods of time without disease progression. Incorporation of these considerations into the design and conduct of future clinical trials in mBC, as well as HTA and reimbursement decision-making, is needed to better capture the potential value of a therapeutic innovation.     

Initial experience with CDK4/6 inhibitor-based therapies compared to antihormone monotherapies in routine clinical use in patients with hormone receptor positive,HER2 negative breast cancer — Data from the PRAEGNANT research network for the first 2 years of drug availability in Germany

PurposeTreatment with CDK4/6 inhibitors and endocrine therapy (CDK4/6i + ET) is a standard for patients with advanced hormone receptor–positive, HER2-negative (HR + HER2–) breast cancer (BC). However, real-world data on the implementation of therapy usage, efficacy, and toxicity have not yet been reported.MethodsThe PRAEGNANT registry was used to identify advanced HR + HER2– BC patients (n = 1136). The use of chemotherapy, ET, everolimus + ET, and CDK4/6i + ET was analyzed for first-line, second-line, and third-line therapy. Progression-free survival (PFS) and overall survival (OS) were also compared between patients treated with CDK4/6i + ET and ET monotherapy. Also toxicity was assessed.ResultsCDK4/6i + ET use increased from 38.5% to 62.7% in the first 2 years after CDK4/6i treatment became available (November 2016). Chemotherapy and ET monotherapy use decreased from 2015 to 2018 from 42.2% to 27.2% and from 53% to 9.5%, respectively. In this early analysis no statistically significant differences were found comparing CDK4/6i + ET and ET monotherapy patients with regard to PFS and OS. Leukopenia was was seen in 11.3% of patients under CDK4/6i + ET and 0.5% under ET monotherapy.ConclusionsIn clinical practice, CDK4/6i + ET has been rapidly implemented. A group of patients with a more unfavorable prognosis was possibly treated in the real-world setting than in the reported randomized clinical trials. The available data suggest that longer follow-up times and a larger sample size are required in order to identify differences in survival outcomes. Studies should be supported that investigate whether chemotherapy can be avoided or delayed in this patient population by using CDK4/6i + ET.     

Acetato de abiraterona prequimioterapia. Propuesta de un algoritmo de tratamiento en el carcinoma de próstata resistente a castración

ContextProstate cancer treatment remains a challenge for the urologist. Medical control in locally advanced or metastatic prostate cancer is usually performed with LHRH analogues and/or antiandrogens. Different treatments have been proposed when there is biochemical and clinical progression of the disease and other new ones have changed the patients’ perspective and life expectancy.ObjectiveThis review has aimed to establish the current role of Abiraterone Acetate in the treatment of castration-resistant prostate cancer and facilitate decision-making by the Urologist by means of a Treatment Algorithm.Acquisition of the evidenceA search of current evidence on Abiraterone treatment in patients with castration- resistant metastatic prostate cancer was performed in PubMed, mainly analyzing those studies designed as clinical trials. In addition, we reviewed and updated the role of hormone therapy and androgen receptors in prostate cancer.Evidence synthesisThere are currently basically two clinical trials that demonstrate the effectiveness of Abiraterone in metastatic prostate cancer compared to placebo. The study COU-AA 302 shows a clear benefit with Abiraterone prior to chemotherapy in patients with castration-resistant prostate cancer, this making it possible to establish an algorithm for initial treatment that facilitates decision-making by the urologist.ConclusionAbiraterone is a pre-chemotherapy treatment option in selected patients with castration resistant metastatic prostate cancer, although it is necessary to improve the cost and to design more multicenter clinical trials to optimize the cost/benefit ratio.     

Hsp90 inhibitors in breast cancer: A systematic review

PurposePharmacological inhibition of Hsp90 shows great promise in breast cancer treatment. This is the first systematic review to synthesize all available data and to evaluate the efficacy and safety of Hsp90 inhibitors in breast cancer.MethodsThis study was performed in accordance with the PRISMA guidelines. Eligible articles were identified by a search of MEDLINE and ClinicalTrials.gov databases, using a predefined combination of the terms “breast”, “cancer”, “Hsp90”, “inhibitors”.ResultsOverall, 19 articles (190 patients) were eligible. The greatest clinical activity has been observed on the field of HER2-positive metastatic breast cancer. However, accumulating data suggest that Hsp90 inhibitors may play a significant role in the treatment of triple negative and aromatase inhibitor-resistant breast cancer.ConclusionIn the last decade, the development of Hsp90 inhibitors has moved forward rapidly; however, no phase III trials have been conducted and none agent has been approved for use in the clinical practice.     

Palbociclib in combination with aromatase inhibitors in patients ≥ 75 years with oestrogen receptor-positive,human epidermal growth factor receptor 2 negative advanced breast cancer: A real-world multicentre UK study

BackgroundBreast cancer incidence increases with age and real-world data is essential to guide prescribing practices in the older population. The aim of this study was to collect large scale real-world data on tolerability and efficacy of palbociclib + AI in the first line treatment of ER+/HER2-advanced breast cancer in those aged ≥75 years.Methods14 cancer centres participated in this national UK retrospective study. Patients aged ≥75 years treated with palbociclib + AI in the first line setting were identified. Data included baseline demographics, disease characteristics, toxicities, dose reductions and delays, treatment response and survival data. Multivariable Cox regression was used to assess independent predictors of PFS, OS and toxicities.Results276 patients met the eligibility criteria. The incidence of febrile neutropenia was low (2.2%). The clinical benefit rate was 87%. 50.7% of patients had dose reductions and 59.3% had dose delays. The 12- and 24- month PFS rates were 75.9% and 64.9%, respectively. The 12- and 24- month OS rates were 85.1% and 74.0%, respectively. Multivariable analysis identified PS, Age-adjusted Charlson Comorbidity Index (ACCI) and number of metastatic sites to be independent predictors of PFS. Dose reductions and delays were not associated with adverse survival outcomes. Baseline ACCI was an independent predictor of development and severity of neutropenia.ConclusionPalbociclib is an effective therapy in the real-world older population and is well-tolerated with low levels of clinically significant toxicities. The use of geriatric and frailty assessments can help guide decision making in these patients.     

Management of Chemotherapy-Induced Nausea and Vomiting with Trastuzumab Deruxtecan: A Case Series

IntroductionTrastuzumab deruxtecan is a monoclonal antibody linked to a chemotherapy moiety that was recently approved by the Food and Drug Administration (FDA) for the treatment of metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancers. There are labeled black box warnings for interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity. Additionally, chemotherapy-induced nausea and vomiting (CINV) was reported to be as high as 78% (∼8% grade 3 or higher) in phase I and II clinical trials. Clinical trial and package insert recommendations for the management of CINV are not available, making real-world management difficult.Case PresentationWe reviewed the first 10 patients who received trastuzumab deruxtecan at our hospital-based community cancer center to determine if CINV management was adequate. We found a rate of 28.9% CINV (all grade 1 and 2) despite treatment as a moderate emetic potential regimen. Interventions by the treatment team to manage trastuzumab deruxtecan as a high-risk emetic regimen resulted in reduced CINV and ongoing treatment for all patients.Discussion and ConclusionThis review indicates that management of CINV for patients receiving trastuzumab deruxtecan should follow recommendations for regimens with a high-risk emetic potential.     

A nationwide,multicenter retrospective study on the effectiveness and safety of eribulin in Korean breast cancer patients (REMARK)

PurposeApproval of eribulin for metastatic breast cancer was based on data primarily from Western patients, and there is a paucity of data on the effectiveness and safety of eribulin for Asian patients. To determine the effectiveness and safety of eribulin in Korean women with breast cancer in a real-world setting, we conducted a nationwide, multicenter, retrospective study.MethodsPatients with locally advanced or metastatic breast cancer who were treated with eribulin in 14 centers throughout Korea were included in this study. Eribulin was generally administered at a dose of 1.23 mg/m² (equivalent to 1.4 mg/m² eribulin mesylate) by intravenous infusion for 2–5 min, or as a diluted solution, on Days 1 and 8 of every 21-day cycle. The primary endpoint was progression-free survival (PFS) rate at 6 months. Secondary endpoints included median PFS, overall survival (OS), time-to-treatment failure (TTF), tumor response rate, and incidence of hematologic treatment-emergent adverse events (TEAEs).ResultsThe safety and full analysis populations included 398 and 360 (38 had no efficacy data) patients, respectively. The PFS rate at 6 months was 37.8%. Median PFS, OS, and TTF were 134, 631, and 120 days, respectively. Objective response rate, clinical benefit rate, and disease control rate were 18.1%, 50.6%, and 49.4%, respectively. Hematologic TEAEs were reported in 65.1% of patients; neutropenia (56.8%) and anemia (11.3%) were most common.ConclusionReal-world effectiveness and safety of eribulin in Korean breast cancer patients were consistent with previous reports; no new safety concerns were identified.     

Slow accrual of elderly patients with metastatic breast cancer in the Dutch multicentre OMEGA study

BackgroundIn a Dutch multicentre study, elderly (65 + year) metastatic breast cancer patients, eligible for first-line chemotherapy, were randomised between two types of single-agent chemotherapy. As accrual was slow, with 78 randomised patients between April 2007 and September 2011, we explored potential barriers in the accrual process and their consequences for characteristics of included patients.MethodsWe sent surveys on the reasons for non-inclusion to all coordinating investigators. We also examined inclusion in a concurrent, non-elderly breast cancer study of the trialists' group and analysed baseline geriatric characteristics of included patients.ResultsInvestigators from fifteen participating centres returned the survey. Most commonly reported barriers to inclusion were: patient's refusal of chemotherapy (n = 8) or of randomisation (n = 9), impaired cognition (n = 3) and insufficient cardiac function (n = 2). Oncologists' preference for combination regimens over single-agent chemotherapy was reported twice. Twenty-eight potentially eligible patients, aged 65–71 years, were included in a concurrent, study investigating combination chemotherapy in fit non-elderly patients with metastatic breast cancer. However, baseline characteristics of the included patients showed that the OMEGA study succeeded in including frail and older patients, with a performance status of 2 in 22% of patients and 54% of patients aged 75 years or older.ConclusionAccrual in this study was mainly hampered by patient's refusal or preference for a particular type of treatment, and an overall condition considered as too fit or too frail for inclusion. Future trials in elderly metastatic breast cancer patients should focus on non-restrictive inclusion criteria as well as on education of physicians and elderly patients on the advantages of trial participation.     

Review of the development of letrozole and its use in advanced breast cancer and in the neoadjuvant setting

Five years of adjuvant endocrine therapy with the antiestrogen tamoxifen has been shown to significantly reduce the risk of recurrence in women with early breast cancer and has thus been the standard of adjuvant therapy for this malignancy over the last two decades. Tamoxifen has also been used for the first-line treatment of advanced or metastatic breast cancer, and it was studied in the neoadjuvant setting to promote breast-conserving surgery in those patients who may be otherwise ineligible. However, comparative clinical trials involving the more recently approved third-generation aromatase inhibitor drugs (anastrozole, letrozole, and exemestane) have challenged tamoxifen as first-line therapy in advanced/metastatic breast cancer as well as in the neoadjuvant setting. Although trials with other AIs have shown improved efficacy and better tolerability over tamoxifen, letrozole has consistently demonstrated superiority over tamoxifen when used as first-line treatment for advanced/metastatic breast cancer or as neoadjuvant therapy. The efficacy of letrozole in the neoadjuvant setting further extends to those tumors with positive human epidermal growth factor receptor (HER1) and/or HER2 expression, which are often less responsive to tamoxifen. The encouraging results of such trials identify letrozole as a better alternative to tamoxifen in improving responses rates in the treatment of advanced breast cancer and as neoadjuvant therapy, which allows breast-conserving surgery in women with inoperable breast cancer or who were not candidates for breast-conserving surgery.     

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease,Biochemical Relapse,and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022

BackgroundInnovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management.ObjectiveTo present consensus voting results for select questions from APCCC 2022.Design, setting, and participantsBefore the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members (“panellists”) who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1–3.Outcome measurements and statistical analysisConsensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement.Results and limitationsThe voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis.ConclusionsThese voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.     

The challenge of sustainability in healthcare systems: Frequency and cost of inappropriate patterns of breast cancer care (the E.Pic.A study)

ObjectivesIn a context of decreasing economic health resources and a rise in health needs, it is urgent to face this sustainability crisis through the analysis of healthcare expenditures. Wastages, deriving from inappropriate interventions, erode resources which could be reallocated to high-value activities. To identify these areas of wastages, we developed a method for combining and analyzing data from multiple sources. Here we report the preliminary results of a retrospective cohort study evaluating the performance of breast cancer (BC) care at IRST, an Italian cancer institute.Materials and methodsFour data sources gathered in a real-world setting (a clinical database, two administrative databases and a cancer registry) were linked. Essential Key Performance Indexes (KPIs) in the pattern of BC diagnosis (KPI 1 and 2) and treatment (KPI 3 and 4) based on current guidelines were developed by a board of professionals. The costs of inappropriate examinations were associated with the diagnostic KPIs.ResultsWe found that 2798 patients treated at IRST from January 2010 to June 2016 received a total of 2516 inappropriate examinations accounting for € 573,510.80. Linkage from multiple routine healthcare data sources is feasible: it allows the measurement of important KPIs specifically designed for BC care, and the identification of areas of low-value use of the resources.ConclusionIf systematically applied, this method could help provide a complete picture of inappropriateness and waste, redirect these resources to higher-value interventions for patients, and fill the gap between proper use of the resources and the best clinical results.     

Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019

BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.ObjectiveTo present the results from the APCCC 2019.Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.     

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

PurposeWe aim to describe the treatment patterns and overall survival (OS) outcomes in patients receiving trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer (HER2+MBC) in routine clinical care.MethodsRetrospective, whole-of-population cohort study of people initiating T-DM1 for HER2+MBC between October 2015 and May 2019 in Australia. We used dispensing claims to estimate time-to-T-DM1 initiation, duration of treatment, and treatments administered prior to and following T-DM1 therapy. We estimated OS from T-DM1 initiation and stratified results based on whether patients received first- or second-line T-DM1 treatment. We benchmarked outcomes to those reported in the pivotal, EMILIA trial.Results345 patients initiated T-DM1: 309 as second-line therapy for HER2+MBC and 36 as first-line therapy. 51% of patients had received endocrine therapy and 98% of second-line patients received pertuzumab prior to starting T-DM1. The median age was 57 years (53 in EMILIA); median time-to-T-DM1 initiation from start of HER2-targeted therapy for HER2+MBC was 11.6 months (IQR: 7.9–16.6); median duration of T-DM1 treatment was 6.5 months (3.1–13.5; 7.6 months in EMILIA), and median OS was 19.3 months (7.9–29.5; 29.9 months in EMILIA).ConclusionsOur findings highlight differences in patient characteristics (older, more previous pertuzumab therapy) and outcomes (shorter OS) from the T-DM1 pivotal trial and provide real-world estimates that can inform patient, clinician and policy, decisions around the use of HER2-targeted therapies in routine clinical care.