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To the Editor: Since our group first reported on the potential clinical applications of the human tumor stem-cell, or clonogenic, assay in the Journal,1 we think some comment from us is warranted regarding the recent article by Selby et al.2 and the editorial by Von Hoff.3 We clearly agree that it is important to plate good single-cell suspensions, that drug-sensitivity criteria are still in the developmental stages,4 that some drugs may require the evaluation of various exposure times, that inappropriate drug concentrations may be misleading, that drugs requiring bioactivation present special problems, that radiation-survival curves with plateaus at. © 1983, Massachusetts Medical Society. All rights reserved.

A commonly reported consequence of post-treatment nausea or vomiting is the development of anticipatory nausea and vomiting (ANV). In most published work, nausea is reported to occur before chemotherapy drugs are administered by approximately 20% of patients at any one chemotherapy cycle and by 25-30% of patients by their fourth chemotherapy cycle. Most studies in adult patients strongly support the view that the development of ANV involves elements of classical conditioning. The best method to avoid development of ANV is to adequately prevent both vomiting and nausea from the first exposure to chemotherapy. If anticipatory side effects develop, behavioral treatment techniques, such as systematic desensitization, have been shown effective. Benzodiazepines used in combination with behavioral techniques or antiemetics may also be useful. The evidence on which these conclusions are based is reviewed in this article. [ABSTRACT FROM AUTHOR]

Anemia is frequently experienced by cancer patients receiving chemotherapy and can negatively impact the patient's prognosis. Blood transfusions, iron supplementation (in absolute or functionally iron-deficient anemias), and erythropoiesis-stimulating agents (ESAs) are among the treatment options for anemia. Treatment options for anemia management should be selected based on the best benefit-to-risk ratio for each individual patient. In September 2007, the working party of the European Organization for Research and Treatment of Cancer (EORTC) updated their guidelines on the use of ESAs, which are summarized in this paper. ESAs reduce the number of transfusions required and significantly improve quality of life in patients with chemotherapy-induced anemia. A sustained hemoglobin level of about 12 g/dl should be the target for treatment with ESAs. ESAs should be used according to the EORTC guidelines and within label with carefully considered exceptions. [ABSTRACT FROM AUTHOR]

The treatment of advanced breast cancer is continually evolving, with the aim of improving the quality and duration of remission and, in some instances, survival. In this setting, the importance of quality of life cannot be underestimated, and growing attention is being paid to treatment convenience and compliance. New anticancer agents have improved efficacy, but for many of them, toxicity often remains a problem. Vinorelbine seems to represent both an active and a well tolerated treatment for metastatic breast cancer. In particular, the oral formulation has similar efficacy to that of the injectable formulation and has demonstrated generally favourable tolerability, with a high degree of acceptance by both patients and physicians. The availability of this and other novel, well tolerated and effective treatments provides greater potential to tailor treatment to meet individual patient needs and, therefore, also provide the potential to improve patient outcomes. Preliminary data suggest that oral vinorelbine may permit continued, effective chemotherapy when further parenteral therapy with more intensive and more toxic agents is considered inappropriate. Early findings also suggest that oral vinorelbine, when administered together with another new oral agent, capecitabine, may be a valid choice in metastatic breast cancer treatment. Furthermore, vinorelbine plus the monoclonal antibody trastuzumab, with or without oral capecitabine, appears to be another regimen that may be worthy of additional study in patients with human epidermal growth factor-2 positive advanced breast cancer. [ABSTRACT FROM AUTHOR]

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast cancer (inoperable locally advanced or metastatic), of all breast cancer subtypes, as well as palliative and supportive care. These guidelines are based on available evidence or on expert opinion when a higher level of evidence is lacking. Each guideline is accompanied by the level of evidence (LoE), grade of recommendation (GoR) and percentage of consensus reached at the consensus conferences. Updated diagnostic and treatment algorithms are also provided. The guidelines represent the best management options for patients living with ABC globally, assuming accessibility to all available therapies. Their adaptation (i.e. resource-stratified guidelines) is often needed in settings where access to care is limited., Competing Interests: Declaration of competing interest Matti S. Aapro: Consultant for Accord Pharmaceuticals, Amgen, BMS, Celgene, Clinigen Group, Daiichi Sankyo, Eisai Co.Ltd, Eli Lilly, Genomic Health (Exact Sciences), G1 Therapeutics, Inc., GlaxoSmithKline (GSK), Helsinn Healthcare SA, Hospira (Pfizer), Johnson & Johnson, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro (GSK), Teva Pharmaceuticals Industries Ltd., Vifor Pharma. Received honoraria for lectures at symposia of Accord Pharmaceuticals, Amgen, Astellas, Bayer HealthCare Pharmaceuticals (Schering), Biocon, Boeringer Ingelheim, Cephalon, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Dr Reddy's Laboratories, Genomic Health (Exact Sciences), Glenmark Pharmaceuticals Limited, GSK, Helsinn Healthcare SA, Hospira (Pfizer), Ipsen, Janssen Biotech, Kyowa Kirin Group, Merck, Merck Serono (Merck KGaA), Mundipharma International Limited, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro (GSK), Taiho Pharmaceutical, Teva Pharmaceutical Industries Ltd., Vifor Pharma. Grant/Research supports: Amgen, Eisai, Genomic Health (Exact Sciences), Helsinn, Hospira, Novartis, Merck, Mundipharma, Pfizer, Roche, Sandoz, Tesaro, Teva, Vifor. Jyoti Bajpai: Institutional financial interests for conducting research: Eli Lilly, MSD, Novartis, Roche, Paxman Coolers Ltd, Samsung Bioepis co. Ltd, Sun Pharma. Carlos H. Barrios: Receipt of grants/research supports: (to the institution) Nektar, Pfizer, Polyphor, Amgen, Daiichi Sankyo, Sanofi, Exelixis, Regeneron, Novartis, GSK, Janssen, OBI Pharma, Lilly, Seagen, Roche, BMS, MSD, Merck Serono, AstraZeneca, Novocure, Aveo Oncology, Takeda, TRIO, PharmaMar, Celgene, PPD, Syneos Health, Labcorp, ICON, IQVIA, Parexel, Nuvisan, PSI, Worldwide, Gilead Sciences, Bayer, Servier. Receipt of honoraria or consultation fees: Advisory Boards and Consulting: Boehringer-Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, Bayer, MSD, AstraZeneca, Zodiac, Lilly, Sanofi, Daiichi. Stock shareholder: Ownership or stocks: Tummi, MEDSir. Jonas Bergh: Receipt of grants/research supports: Research grants from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche & Sanofi-Aventis to Karolinska Institutet and/or University Hospital. No personal payments. Other support: Payment for a chapter in UpToDate on breast cancer prediction to Asklepios Medicin HB. Laura Biganzoli: Personal financial interests (Honoraria, consultancy or advisory role): Amgen, AstraZeneca, Boehringer-Ingelheim, Daiichi-Sankyo, Eisai, Exact Sciences, Gilead, Lilly, Menarini, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, SeaGen. Institutional financial interests: Celgene, Genomic Health, Novartis. Travel grants: AstraZeneca, Daiichi-Sankyo. Fatima Cardoso: Receipt of honoraria or consultation fees: Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi-Sankyo, Eisai, GE Oncology, Genentech, Gilead, GlaxoSmithKline, Iqvia, Macrogenics, Medscape, Merck-Sharp, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre-Fabre, prIME Oncology, Roche, Sanofi, Samsung Bioepis, Seagen, Teva, Touchime. Maria-Joao Cardoso: Receipt of honoraria or consultation fees: AstraZeneca, Merck-Sharp, Novartis and Roche. Lisa A. Carey: Other support: Research funding (institution): NanoString Technologies, Seagen, Veracyte, AstraZeneca. Uncompensated relationships: Lilly, Seagen, Novartis, Genentech/Roche, GlaxoSmithKline. Mariana Chavez-MacGregor: Receipt of grants/research supports: BCRF, Susan G Komen. Receipt of honoraria or consultation fees: Astra Zeneca, Pfizer, Lilly, Roche, Merck. Javier Cortés: Receipt of grants/research supports: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics, Expres2ion Biotechnologies. Receipt of honoraria or consultation fees: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo, Astrazeneca. Stock shareholder: MedSIR, Nektar Pharmaceuticals, Leuko (relative). Other support: Research funding to the Institution: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London. Travel, accommodation, expenses: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca, Gilead. Patents: Pharmaceutical Combinations of a Pi3k Inhibitor and A Microtubule Destabilizing Agent. Javier Cortés Castán, Alejandro Piris Giménez, Violeta Serra Elizalde. WO 2014/199294 A. ISSUED. Her2 as a predictor of response to dual HER2 blockade in the absence of cytotoxic therapy. Aleix Prat, Antonio Llombart, Javier Cortés.US 2019/0338368 A1. LICENSED. Giuseppe Curigliano: Receipt of grants/research supports: Merck. Receipt of honoraria or consultation fees: Merck, Lilly, Pfizer, Daichi Sankyo, Seagen, Novartis, Roche, Astra Zeneca, Ellipsis. Participation in a sponsored speakers' bureau: Seagen, Novartis, Lilly, Pfizer, Daichii Sankyo. Rebecca A. Dent: Receipt of grants/research supports: AstraZeneca, Roche. Receipt of honoraria or consultation fees: AstraZeneca, DKSH, Eisai, Merck, Novartis, Pfizer, Roche. Nagi S. El Saghir: Receipt of honoraria or consultation fees: Roche, Novartis, Lilly. Alexandru Eniu: Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi Sankyo, Gilead, Janssen, MSD, Novartis, SeaGen. Receipt of grants/research supports: AstraZeneca. Full or part-time employment: European School of Oncology (ESO). Lesley Fallowfield: Receipt of grants/research supports: Novartis, Bristol-Myers Squibb, Lilly. Receipt of honoraria or consultation fees: Voluntis, Genomic Health, NanoString Technologies, Novartis, Pfizer, MSD, Novartis, Abbvie, Clovis Oncology, Puma Biotechnology, AstraZeneca, Takeda, Genomic Health/Exact Sciences, Lilly, Seagen, Roche. Sandra X. Franco Millan: Receipt of honoraria or consultation fees: Novartis, Pfizer, Eli Lilly. Participation in a sponsored speakers' bureau: Novartis, Pfizer, Eli Lilly. Karen Gelmon: Receipt of grants/research supports: Pfizer, AstraZeneca. Receipt of honoraria or consultation fees: Pfizer, Lilly, Novartis, AstraZeneca, Merck, Gilead, Seagen. Jenny Gilchrist: Receipt of honoraria or consultation fees: Eli-Lilly, AstraZeneca, Novartis, Pfizer, MSD, Gilead, Juniper Biologics. Joseph Gligorov: Receipt of grants/research supports: Eisai, Exact Science, Guardant, Roche Genentech. Receipt of honoraria or consultation fees: Astra Zeneca, Daiichi, Eisai, Evapharma, Exact Science, Gilead, Guardant Lilly, Merck, Novartis, Onxeo, Pfizer, Roche Genentech, Seattle Genetics. Participation in a sponsored speakers' bureau: Eisai, Eva Pharm, Novartis, Roche Genentech, Seattle Genetics. Other support (please specify): Institutional: Institut Universitaire de Cancérologie AP-HP Sorbonne Université; French breast cancer guidelines St Paul. Nadia Harbeck: Receipt of grants/research supports: all to institution. Receipt of honoraria or consultation fees: AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, PierreFabre, Pfizer, Roche, Sandoz, Seagen, Viatris, Zuelligpharma. Participation on a sponsored speakers' bureau: EPG Communication, MEDSCAPE, Springer. Stock shareholder: WSG minority ownership. Spouse/Partner: Consulting for WSG. Ranjit Kaur: Receipt of grants/research supports: Novartis, Roche, Pfizer, Astrazeneca. Receipt of honoraria or consultation fees: Novartis, Roche, Pfizer, Astrazeneca. Participation in a sponsored speakers' bureau: Novartis, Roche, Pfizer, Astrazeneca. Belinda Kiely: Receipt of honoraria or consultation fees: Speakers fees: Novartis, Eisai. Advisory boards: Roche, Gilead, Novartis. Other support (please specify): meeting registrations fees: Novartis, Pfizer, MSD. Sung-Bae Kim: Receipt of grants/research supports: Novartis, Sanofi-Aventis, and DongKook Pharm Co. Receipt of honoraria or consultation fees: Novartis, AstraZeneca, Lilly, Dae Hwa Pharmaceutical Co. Ltd, ISU Abxis, OBI pharma, Beigene and Daiichi-Sankyo. Stock shareholder: Genopeaks. Smruti Koppikar: Receipt of honoraria or consultation fees: Eli Lilly, Novartis, Cipla, Roche. Participation in a sponsored speakers' bureau: Eli Lilly, Novartis, Cipla, Roche. Marion Kuper-Hommel: Receipt of honoraria or consulting fees: Astra Zeneca. Ginny Mason: Participation in a sponsored speakers' bureau: Novartis. Volkmar Mueller: Receipt of grants/research supports: Institutional research support from Novartis, Roche, Seagen, Genentech, Astra Zeneca. Receipt of honoraria or consultation fees: Speaker honoraria: Astra Zeneca, Daiichi-Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead, Pierre Fabre. Consultancy honoraria from Roche, Pierre Fabre, Amgen, ClinSol, Novartis, MSD, DaiichiSankyo, Eisai, Lilly, Sanofi, Seagen, Gilead, Stemline, ClinSol. Other support (please specify): Travel grants: Roche, Pfizer, Daiichi Sankyo, Gilead. Claire Myerson: Receipt of honoraria or consultation fees: Novartis Pharma. Silvia Neciosup: Receipt of grants/research supports: Roche, Pfizer. Participation in a sponsored speakers' bureau: Tecnofarma, AZ, Roche, Pfizer. Larry Norton: Receipt of honoraria or consultation fees: Blackrock QLS Advisors, Cold Spring Harbor Laboratory, UNC Breast Spore EAB Meeting, Codagenix Scientific Advisory Board Meeting, Martell Diagnostic Laboratories, Inc., Celgene, Agenus, Immix Biopharma, Inc. Shinji Ohno: Participation in a sponsored speakers' bureau: Chugai, Lilly, MSD, Nippon Kayaku. Shani Paluch-Shimon: Receipt of grants/research supports: Pfizer. Receipt of honoraria or consultation fees: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead, Rhenium/Exact Sciences, Stemline, Daichi Sankyo. Participation in a sponsored speakers' bureau: Pfizer, Lily, Novartis, Astra Zeneca, Roche, MSD, Gilead. Ann H. Partridge: Uptodate Royalties. Aleix Prat: Receipt of grants/research supports: Boehringer, Novartis, Roche, Nanostring, Sysmex Europa GmbH, Medica Scientia inno. Research, SL, Celgene, Astellas and Pzifer. Receipt of honoraria or consultation fees: Roche, Pfizer, Novartis, Amgen, BMS, Puma, Oncolytics Biotech, MSD, Guardan Health, Peptomyc and Lilly, Nanostring Technologies and Daiichi Sankyo. Other support: Clinical trials: Boehringer, Lilly, Roche, Novartis, Amgen and Daiichi Sankyo. Hope S. Rugo: Receipt of grants/research supports: Astellas Pharma Inc.; AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; GlaxoSmithKline; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Pionyr Immunotherapeutics; Sermonix Pharmaceuticals Inc.; Taiho Oncology, Inc. and Veru Inc. Receipt of honoraria or consultation fees: Puma, NAPO, Blueprint, and Scorpion Therapeutics Daichi Sankyo. Elzbieta Senkus: Receipt of honoraria or consultation fees: AstraZeneca, Curio Science, Egis, Eli Lilly, Gilead, high5md, MSD, Novartis, Pfizer, Roche, Swixx. Other support: travel support: AstraZeneca, Egis, Gilead, Novartis, Roche. Contracted research: Amgen, AstraZeneca, Eli Lilly, Gilead, Novartis, OBI Pharma, Roche, Samsung, Seagen. Medical writing: AstraZeneca, Eli Lilly. Royalties: Springer. Sandra M. Swain: Receipt of grants/research supports: Kailos Genetics, Genentech/Roche. Receipt of honoraria or consultation fees: Athenex, AstraZeneca, Biotheranostics, Natera, Exact Sciences, Lilly, Merck, Genentech/Roche, Sanofi, Daiichi Sankyo, Molecular Templates, Napo Pharmaceuticals. Stock shareholder: SEAGEN. Other support: CO- PI of INAVO 122 Genentech/Roche with in-kind travel to investigator meetings, Travel related expenses in kind Sanofi and Daiichi Sankyo. Peter Vuylsteke: Receipt of grants/research supports: UICC grant. Receipt of honoraria or consultation fees: Roche, Novartis and MSD. Theresa Wiseman: Receipt of grants/research supports: Receiver of SPCC Pfizer grant. Binghe Xu: Receipt of grants/research supports: sponsored research to my institution from Roche, AstraZeneca and Pfizer. Receipt of honoraria or consultation fees: advisory or consultancy fees from Novartis and Roche. Participation in a sponsored speakers' bureau: speakers’ bureau fees from AstraZeneca, Pfizer, Roche, Eisai. Elizabeth Bergsten-Nordström, Alberto Costa, Runcie C. W. Chidebe, Prudence A. Francis, Xichun Hu, Renate Haidinger, Leonor Matos, Shirley A. Mertz, Birgitte V. Offersen, Olivia Pagani, Eva Schumacher-Wulf, Daniel A. Vorobiof, Frédéric E. Lecouvet, and Eric P. Winer reported no significant relationships. William J. Gradishar, George W. Sledge and Christoph Thomssen have not submitted a disclosure of interests’ form., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Biosimilars have improved access to biologic medicines; however, historical thinking may jeopardize the viability of future markets., Areas Covered: An expert panel of eight diverse European stakeholders provided insights about rethinking biosimilars and cost-savings, reducing patient access inequalities, increasing inter-market equity, and improving education. The insights reported here (Part 2) follow a study that provides perspectives on leveraging the holistic benefits of biosimilars for market sustainability based on independent survey results and telephone interviews of stakeholders from diverse biosimilar markets (Part 1). Directional recommendations are provided for payers., Expert Opinion: The panel's market maturity framework for biosimilars has three stages: 'Invest,' 'Expand' and 'Harvest.' Across market stages, re-thinking the benefits of biosimilars beyond cost-savings, considering earlier or expanded access/new indications, product innovations, and re-investment of biosimilar-generated cost-savings should be communicated to stakeholders to promote further engagement. During 'Expand' and 'Harvest' stages, development of efficient, forward-looking procurement systems and mechanisms that drive uptake and stabilize competition between manufacturers are key. Future biosimilars will target various therapy areas beyond those targeted by existing biosimilars. To ensure a healthy, accessible future market, stakeholders must align their objectives, communicate, collaborate, and coordinate via education, incentivization, and procurement, to maximize the totality of benefits.

Introduction: Approved biosimilars exhibit comparable efficacy, safety, and immunogenicity to reference products. This report provides perspectives on the societal value of biosimilars within Europe and potential factors that have influenced market dynamics., Methods: An independent, self-administered survey or one-on-one in-depth interview was used to collect viewpoints about the impact of biosimilar medicines within European markets. Key insights were also sought from an expert panel of European stakeholders., Results: Survey respondents were clinicians, pharmacists, and payers from Europe ( N  = 103). Perceived benefits of biosimilars included increased access to innovative medicines (73% of respondents) or biologic treatments (66%). Biosimilar competition was thought to expand access to biologics (~50% of respondents) or drug combinations (~36%) and reduce biologic access time (34%). Key drivers of biologic access after biosimilar competition included increased biologic awareness (51%) and changes to prescribing guidelines (37%) and/or treatment paradigms (28%). The expert panel developed a market maturity framework of biosimilar adoption/opportunities comprising three stages: 'Invest,' 'Expand,' and 'Harvest.' Findings were supported by published literature., Conclusions: In Europe, the perceptions of well-informed survey/interview respondents are that biosimilars have improved patient outcomes via increased access to biologics and innovative biologic products, contributing to earlier and longer treatment of a broader population.

Purpose: Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany., Methods: A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty., Results: Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim., Conclusions: Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany., (© 2023. The Author(s).)

Purpose: The oral, α-specific phosphatidylinositol-3-kinase (PI3Kα) inhibitor alpelisib is the first PI3K inhibitor approved for the treatment of advanced breast cancer. As alpelisib is a relatively new therapeutic option, specific guidance and a multidisciplinary approach are needed to provide optimal patient care. The primary objective of this manuscript is to provide comprehensive guidance on minimizing and managing adverse events (AEs) for patients with advanced breast cancer who are receiving alpelisib., Methods: Clinical studies, prescribing information, published literature, and relevant guidelines were reviewed to provide recommendations on the prevention and management of alpelisib-associated AEs., Results: The most common AEs associated with alpelisib in the phase 3 SOLAR-1 trial were hyperglycemia and rash (which are considered on-target effects of PI3Kα inhibition) and gastrointestinal AEs, including diarrhea, nausea, and decreased appetite. These AEs require regular monitoring, early recognition, and prompt initiation of appropriate treatment. In addition, there are effective strategies to reduce the onset and severity of frequently observed AEs-in particular, onset of hyperglycemia and rash may be reduced by lifestyle changes (such as reduced intake of carbohydrates and regular exercise) and antihistamine prophylaxis, respectively. To reduce risk of severe hyperglycemia, it is essential to achieve adequate glycemic control prior to initiation of alpelisib treatment., Conclusion: Overall, alpelisib-associated AEs are generally manageable with prompt recognition, regular monitoring, and appropriate intervention, preferably with a multidisciplinary approach., Competing Interests: Declaration of competing interest H.S. Rugo: Institution research funding from Pfizer, Novartis, Eli Lilly, Genentech, MacroGenics, Merck, OBI Pharma, Eisai, Immunomedics, Daiichi, Odonate, and Seattle Genetics; travel support from Daiichi, AstraZeneca, Novartis, Pfizer, Mylan, and Merck; consulting/advisory income from Puma and Celltrion. M.E. Lacouture: Consulting from Novartis, Varsona, Innovaderm, Novocure, QED, Seagen, Lutris, DFB, JnJ, Deciphera, Onquality, TWIBiotech, Azitra, Janssen, EMD Serono, and Bicara; research funding from Novartis, AZ, JnJ, Onquality, and Novocure. M.D. Goncalves: Personal fees from Novartis, grants from Pfizer, and personal fees from Petra Pharma, Scorpion Therapeutics, and Faeth Therapeutics, outside the submitted work; patent (pending) for Combination Therapy for PI3K-associated Disease or Disorder, and patent for The Identification of Therapeutic Interventions to Improve Response to PI3K Inhibitors for Cancer Treatment pending; and owns stock in Faeth Therapeutics. U. Masharani: Research funding from Clementia Pharmaceuticals. M.S. Aapro: Consulting/advisory role in Amgen, BMS, Daiichi Sankyo, Fresenius Kabi, G1 Therapeutics, Genomic Health, Helsinn Healthcare, Merck, Merck KGaA, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, and Vifor Pharma; speakers' bureau at Accord Research, Amgen, Biocon, Dr Reed, Genomic Health, Helsinn Healthcare, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Taiho Pharmaceutical, Tesaro, and Vifor Pharma; research funding from Helsinn Healthcare, Novartis, Pierre Fabre, and Sandoz. J.A. O'Shaughnessy: Personal fees from AbbVie, Agendia, Amgen, AstraZeneca, Bristol-Myers Squibb, Celgene, Eisai, Genentech, Genomic Health, GRAIL, Immunomedics, Heron Therapeutics, Ipsen Biopharmaceuticals, Jounce Therapeutics, Lilly, Merck, Myriad, Novartis, Ondonate Therapeutics, Pfizer, Puma Biotechnology, Prime Oncology, Roche, Seattle Genetics, and Syndax Pharmaceuticals, outside the submitted work., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated., Competing Interests: Declaration of interests LB reports personal fees from AstraZeneca, Eisai, Lilly, Pierre Fabre, and Daiichi Sankyo; grants, personal fees, and non-financial support from Celgene, Ipsen, and Pfizer; grants and personal fees from Genomic Health and Novartis; and personal fees and non-financial support from Roche, outside the submitted work. NLMB reports grants and personal fees from Pfizer and grants from Genomic Health, outside the submitted work. HW reports that his institution (University Hospitals Leuven, Leuven, Belgium) received consulting fees and honoraria from AstraZeneca, Biocartis, Lilly, Novartis, Pfizer, PUMA Biotechnology, Roche, Sirtex, and Daiiji; the institution received unrestricted research grants from Roche and Novartis; and HW received travel support from Roche and Pfizer. MSA reports personal fees and non-financial support from the Multinational Association for Supportive Care in Cancer, European Society of Medical Oncology, and European CanCer Organisation; grants and personal fees from Helsinn, Sandoz; and personal fees from Tesaro, Merck, Vifor, Pfizer, Taiho, and Kyowa Kirin, outside the submitted work. EGCB reports personal fees from Pfizer, Roche, Samsung, Pierre Fabre, Novartis, AstraZeneca, TLC PharmaChem, Clinigen, Mylan, and G1 Therapeutics; and grants and personal fees from Bristol Myers Squibb, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

BRCA1 and BRCA2 gene pathogenic variants account for most hereditary breast cancer and are increasingly used to determine eligibility for PARP inhibitor (PARPi) therapy of BRCA-related cancer. Because issues of BRCA testing in clinical practice now overlap with both preventive and therapeutic management, updated and comprehensive practice guidelines for BRCA genotyping are needed. The integrative recommendations for BRCA testing presented here aim to (1) identify individuals who may benefit from genetic counselling and risk-reducing strategies; (2) update germline and tumour-testing indications for PARPi-approved therapies; (3) provide testing recommendations for personalised management of early and metastatic breast cancer; and (4) address the issues of rapid process and tumour analysis. An international group of experts, including geneticists, medical and surgical oncologists, pathologists, ethicists and patient representatives, was commissioned by the French Society of Predictive and Personalised Medicine (SFMPP). The group followed a methodology based on specific formal guidelines development, including (1) evaluating the likelihood of BRCAm from a combined systematic review of the literature, risk assessment models and expert quotations, and (2) therapeutic values of BRCAm status for PARPi therapy in BRCA-related cancer and for management of early and advanced breast cancer. These international guidelines may help clinicians comprehensively update and standardise BRCA testing practices., Competing Interests: Conflicts of interest The development of these guidelines was wholly funded by SFMPP. The panelists received no payments. The complete CoI for researchers who contributed to the guidelines are provided in supplementary data. Categories for disclosure of CoI include employment; leadership; stock or other ownership; honoraria, consulting or advisory role; speaker’s bureau; research funding; patents, royalties, other intellectual property; expert testimony; travel, accommodations, expenses; and other relationships., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: Disclosure MSA reports receipt of consultation fees from Amgen, BMS, Celgene, Clinigen, Eisai, Genomic Health, GSK, Helsinn, Hospira, JnJ, Novartis, Merck, Merck Serono, Mundipharma, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro, Tevam Vifor, G1 Therapeutics and Lilly; receipt of honoraria for symposia lectures from Amgen, Bayer, Schering, Cephalon, Chugai, Eisai, Genomic Health, GSK, Helsinn, Hospira, Ipsen, JnJ Ortho Biotech, Kyowa Hakko Kirin, Merck, Merck Serono, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro, Taiho, Tevam Vifor, G1 Therapeutics and Lilly. CHB reports receipt of honoraria or consultation fees from Boehringer Ingelheim, GSK, Novartis, Pfizer, Roche/Genentech, Eisai, MSD, AstraZeneca and Bayer; receipt of grants/research support to the institution from AbbVie, Amgen, Astellas Pharma, AstraZeneca, BMS, Celgene, Covance, Lilly, Medivation, Merck Serono, MSD, Novartis, Pfizer, PharmaMar and Roche/Genentech. JB reports receipt of grants/research support grants to Karolinska Institute and University Hospital from Amgen, AstraZeneca, Bayer, Merck, Pfizer, Roche, Sanofi-Aventis; no personal payments; payment from UpToDate to Asklepios Medicine HB for a chapter on breast cancer prediction. LB reports receipt of grants/research support from Celgene, Genomic Health and Novartis; receipt of honoraria or consultation fees from AstraZeneca, Celgene, Daiichi Sankyo, Eisai, Genomic Health, Ipsen, Lilly, Novartis, Pfizer, Pierre Fabre and Roche. FC reports receipt of honoraria or consultation fees from Amgen, Astellas/Medivation, AstraZeneca, Celgene, Daiichi Sankyo, Eisai, GE Oncology, Genentech, GSK, MacroGenics, Medscape, MSD, Merus BV, Mylan, Mundipharma, Novartis, Pfizer, Pierre Fabre, prIME Oncology, Roche, Sanofi, Seattle Genetics and Teva. JC reports acting as a consultant/advisor for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, MSD, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim and Kyowa Kirin; received honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MSD and Daiichi Sankyo; received research funding to the institution from Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffmann-La Roche, Guardant Health, MSD, Pfizer, PIQUR Therapeutics, Puma C and Queen Mary University of London; holds stock, patents and intellectual property for MEDSIR; received travel, accommodation and expenses from Roche, Novartis, Eisai, Pfizer and Daiichi Sankyo. GC reports receipt of honoraria or consultation fees from Roche, Pfizer, Lilly, Novartis and SeaGen; participation in a sponsored speakers' bureau for SeaGen, Pfizer, Lilly and Novartis. NSES reports receipt of grants/research support to institution from Novartis; receipt of honoraria or consultation fees from Novartis, Roche, Pfizer, Lilly and AstraZeneca. ME reports acting in an advisory role for Novartis and Roche. AE reports receipt of grants/research support from AstraZeneca, Roche, Celltrion, Pfizer and Novartis. LF reports receipt of grants/research support from BMS, GSK, Myriad and Novartis; receipt of honoraria or consultation fees from BMS, AstraZeneca, Teva, Novartis, Eisai, Takeda, Pfizer, Lilly, Genomic Health and Myriad. PAF reports receipt of honoraria or consultation fees from AstraZeneca and Novartis; travel for lecture for Pfizer and Ipsen. KG reports receipt of grants/research support from AstraZeneca, Pfizer and BMS; receipt of honoraria or consultation fees from Pfizer, AstraZeneca, Novartis, Nanostring, Merck, Mylan, Genomic Health, Roche and BMS. JG reports receipt of grants/research support from Amgen, Eisai, Genomic Health, Novartis, Pfizer and Roche/Genentech; receipt of honoraria or consultation fees from Daiichi, Eisai, Genomic Health, Ipsen, MacroGenics, MSD, Mylan, Novartis, Onxeo, Pfizer and Roche/Genentech; participation in a sponsored speakers' bureau for Eisai, Genomic Health, Ipsen, Novartis, Pfizer and Roche/Genentech. NH reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Celgene, Daiichi Sakyo, Lilly, MSD, Novartis, Odonate, Pfizer, Roche, Sandoz/Hexal and Seattle Genetics. RK reports receipt of grants/research support from Pfizer Malaysia. BEK reports receipt of grants/research support to institution from Roche; receipt of honoraria for advisory boards and educational presentations as well as travel and meeting expenses from Roche; receipt of honoraria for advisory boards and educational presentations from Novartis. SBK reports receipt of grants/research support to institution from Novartis, Sanofi-Aventis, Kyowa Kirin Inc. and DongKook Pharm Co.; receipt of consultancy fees from Novartis, AstraZeneca, Lilly, Enzychem, Daehwa Pharmaceutical Co. Ltd, ISU ABXIS and Daiichi Sankyo. NUL reports receipt of grants/research support from Genentech and Seattle Genetics; receipt of honoraria or consultation fees from Seattle Genetics, Daiichi Sankyo and Puma. SAM reports receipt of honoraria from Pfizer and Lilly; SN reports receipt of grants/research support from Roche, Pfizer, BMS and Novartis; participation in a sponsored speakers' bureau for Roche, Pfizer, BMS, Merck and Novartis. LN reports receipt of honoraria from Sermonix Oncology Ad Board, Prime Oncology, Sarah Lawrence Lecture, Context advisory board, Oncology Pioneers Science Lecture Series, BCRF programmatic review meeting and CSHL external advisory board meeting. SO reports receipt of grants/research support from Chugai, Eisai, Taiho, Daiichi Sankyo; participation in a sponsored speakers' bureau for Chugai, AstraZeneca, Eisai, Taiho, Pfizer and Lilly. OP reports participation in a sponsored speakers' bureau for Takeda, Roche, Pfizer, Novartis and Lilly. SPS has participated in a speakers' bureau and received honoraria from Roche, AstraZeneca, Novartis, Pfizer, Nanostring and Teva; reports consultancy for Roche, AstraZeneca, Novartis and Pfizer. FPL reports receipt of grants/research support from Roche; receipt of honoraria or consultation fees from Roche, Puma, Pierre Fabre and AstraZeneca. AP reports personal financial interests and lecture fees for Roche, Pfizer, Novartis, Amgen, BMS and Daiichi Sankyo; participation in an advisory role/consultancy for Roche, Pfizer, Novartis, Amgen, BMS, Puma and Oncolytics Biotech; institutional financial interests include contracted research for Novartis, Nanostring, Roche and Boehringer; lecture fees from Nanostring technologies; clinical trials for Novartis, Roche, Boehringer, Daiichi Sankyo, Pfizer, Lilly and Amgen. HSR reports receipt of grants/research support from Pfizer, Merck, Novartis, Lilly, Genentech, OBI, Odonate, Daiichi Sankyo, Eisai, Seattle Genetics, MacroGenics and Immunomedics. ES reports receipt of honoraria or consultation fees from Amgen, AstraZeneca, Clinigen, Egis, Eli Lilly, Genomic Health, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz and TLC Biopharmaceuticals; travel support from Amgen, AstraZeneca, Egis, Novartis, Pfizer and Roche; contracted research for Amgen, AstraZeneca, Boehringer, Eli Lilly, Merck, Novartis, Pfizer, Roche and Samsung; holds stock in Eli Lilly. EPW reports receipt of grants/research support from Merck and Genentech/Roche; receipt of honoraria or consultation fees from Carrick Therapeutics, Genentech/Roche, Genomic Health, GSK, Jounce, Leap, Lilly, Merck and Seattle Genetics; research fees to institute from Genentech/Roche and Merck; participation in a scientific advisory board for Leap. BX reports receipt of advisory fees from Novartis and Roche; fees for serving on a speakers' bureau from AstraZeneca, Pfizer, Roche and Eisai. FA, FB, BK, FEL, GWS, CT and TW have not reported any potential conflict of interest. GSB, MJC, LAC, AC, RH, XH, BVO and DAV have declared no significant conflict of interest.

Introduction: Chemotherapy-induced myelosuppression (CIM) is one of the most common dose-limiting complications of cancer treatment, and is associated with a range of debilitating symptoms that can significantly impact patients' quality of life. The purpose of this study was to understand patients' perspectives on how the side effects of CIM are managed in routine clinical practice., Methods: An online survey was conducted of participants with breast, lung, or colorectal cancer who had received chemotherapy treatment within the past 12 months, and had experienced at least one episode of myelosuppression in the past year. The survey was administered with predominantly close-ended questions, and lay definitions of key terms were provided to aid response selection., Results: Of 301 participants who completed the online survey, 153 (51%) had breast cancer, 100 (33%) had lung cancer, and 48 (16%) had colorectal cancer. Anemia, neutropenia, lymphopenia, and thrombocytopenia were reported by 61%, 59%, 37%, and 34% of participants, respectively. Most participants (79%) reported having received treatment for CIM, and 64% of participants recalled chemotherapy dose modifications as a result of CIM. Although most participants believed their oncologist was aware of the side effects of CIM, and treated them quickly, 30% of participants felt their oncologists did not understand how uncomfortable they were due to the side effects of CIM. Overall, 88% of participants considered CIM to have a moderate or major impact on their lives., Conclusion: The data highlight that despite the various methods used to address CIM, and the patient-focused approach of oncologists, the real-world impact of CIM on patients is substantial. Improving communication between patients and health care providers may help improve patients' understanding of CIM, and foster shared decision-making in terms of treatment. Additional insights from patients should be obtained to further elucidate the totality of life burden associated with CIM.

Background: Several guidelines have been reported for bone-directed treatment in women with early breast cancer (EBC) for averting fractures, particularly during aromatase inhibitor (AI) therapy. Recently, a number of studies on additional fracture related risk factors, new treatment options as well as real world studies demonstrating a much higher fracture rate than suggested by randomized clinical controlled trials (RCTs). Therefore, this updated algorithm was developed to better assess fracture risk and direct treatment as a position statement of several interdisciplinary cancer and bone societies involved in the management of AI-associated bone loss (AIBL)., Patients and Methods: A systematic literature review identified recent advances in the management of AIBL. Results with individual agents were assessed based on trial design, size, follow-up, and safety., Results: Several fracture related risk factors in patients with EBC were identified. Although, the FRAX algorithm includes fracture risk factors (RF) in addition to BMD, it does not seem to adequately address the effects of AIBL. Several antiresorptive agents can prevent and treat AIBL. However, concerns regarding compliance and long-term safety remain. Overall, the evidence for fracture prevention is strongest for denosumab 60 mg s.c. every 6 months. Additionally, recent studies as well as an individual patient data meta-analysis of all available randomized trial data support additional anticancer benefits from adjuvant bisphosphonate treatment in postmenopausal women with a 34% relative risk reduction in bone metastasis and 17% relative risk decrease in breast cancer mortality that needs to be taken into account when advising on management of AIBL., Conclusions: In all patients initiating AI treatment, fracture risk should be assessed and recommendation with regard to exercise and calcium/vitamin D supplementation given. Bone-directed therapy should be given to all patients with a T-score<-2.0 or with a T-score of <-1.5 SD with one additional RF, or with ≥2 risk factors (without BMD) for the duration of AI treatment. Patients with T-score>-1.5 SD and no risk factors should be managed based on BMD loss during the first year and the local guidelines for postmenopausal osteoporosis. Compliance should be regularly assessed as well as BMD on treatment after 12 - 24 months. Furthermore, because of the decreased incidence of bone recurrence and breast cancer specific mortality, adjuvant bisphosphonates are recommended for all postmenopausal women at significant risk of disease recurrence.

Purpose: This review summarizes the recommendations for the prophylaxis of nausea and vomiting in adults receiving highly emetogenic chemotherapy (HEC) which includes cisplatin, mechlorethamine, streptozocin, cyclophosphamide >1500 mg/m 2 , carmustine, dacarbazine, and the combination of an anthracycline and cyclophosphamide (AC) administered to women with breast cancer, as agreed at the MASCC/ESMO Antiemetic Guidelines Update meeting in Copenhagen in June 2015., Methods: A systematic review of the literature using PubMed and the Cochrane Database from 2009 to June 2015 was performed., Results: The NK 1 -receptor antagonists netupitant (300 mg given in combination with palonosetron 0.5 mg as NEPA) and rolapitant have both completed phase II and III programs and were approved by FDA (both) and EMA (NEPA) in 2014-2015. Addition of one of these agents (or of (fos)aprepitant) to a combination of a serotonin (5-HT) 3 -receptor antagonist and dexamethasone improved the number of patients with a complete response (no emesis and no rescue medication) days 1-5 after AC HEC with 8-9 % and after non-AC HEC by 8-20 %. Olanzapine has improved control of delayed nausea as compared to aprepitant in a randomized open designed study. In the prophylaxis of delayed nausea and vomiting, metoclopramide is an option instead of aprepitant in patients receiving cisplatin-based chemotherapy and dexamethasone is an option instead of aprepitant in patients receiving AC chemotherapy., Conclusions: Two new NK 1 -receptor antagonists (netupitant and rolapitant) have been included in the updated recommendations as additional options to aprepitant or fosaprepitant. Addition of one of these NK 1 -receptor antagonists to a combination of a 5-HT 3 -receptor antagonist and dexamethasone is recommended in both non-AC HEC and AC HEC. Olanzapine is included as an option in HEC in particular if nausea is the main symptom.

Chemotherapy-induced nausea and vomiting (CINV) is among the most feared and debilitating adverse events experienced by cancer patients. Left unaddressed, CINV symptoms not only decrease quality of life, but may also affect patients' willingness to continue chemotherapy treatment. Detailed guidelines are available that outline best practices for prophylaxis of acute and delayed CINV. However, adherence to guideline recommendations continues to be suboptimal, and many patients still suffer unnecessarily from CINV. In addition, breakthrough/refractory CINV continues to present particular challenges. The development of effective CINV treatments with diverse mechanisms of action has expanded the options available for preventing symptoms. The US Food and Drug Administration has recently approved several new therapies for the management of CINV. NEPA is a fixed-dose combination of netupitant(300 mg) plus palonosetron (0.5 mg). In combination with dexamethasone, NEPA has demonstrated superior efficacyto palonosetron alone in patients receiving highly or moderately emetogenic chemotherapy. Rolapitant is a next generation neurokinin 1 (NK1) receptor antagonist. Both palonosetron and rolapitant have proven particularly effective in controlling delayed CINV. Regimens that combine a serotonin 5-hydroxytryptamine–3 receptor antagonist, an NK1receptor antagonist, and a corticosteroid now represent the standard of care for managing both acute and delayed CINV in patients receiving highly emetogenic chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) remains one of the most challenging adverse events of chemotherapy, and one that has substantial negative effects on patients, clinicians, and the wider health care system. Use of CINV prophylaxis consistent with clinical practice guidelines is essential for attaining optimal CINV control. In recent years, there has been a dramatic improvement in the control of CINV with the introduction of effective antiemetic agents, including the serotonin (5-hydroxytryptamine [5-HT3]) receptor antagonists (ondansetron, granisetron, and palonosetron) and the neurokinin-1 (NK1) receptor antagonists (aprepitant and fosaprepitant). An important benefit of the newer antiemetic agents is their improved ability to control the delayed CINV that can develop in the days after chemotherapy administration. In October 2014, a fixed-dose oral combination containing the novel NK1 receptor antagonist netupitant and palonosetron (NEPA) received approval from the US Food and Drug Administration. The combination of 2 effective antiemetic agents in a single, oral capsule may help simplify CINV management. Ongoing studies are evaluating new CINV approaches (eg, the novel NK1 receptor antagonist rolapitant), as well as the optimal use of existing therapies. Patient education regarding the timing, prevention, and treatment of CINV is another key component of CINV management.

Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available. This consensus statement describes twelve key recommendations for supportive care during treatment in low- and middle-income countries, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment. Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adherence to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Chemotherapy regimens differ according to the tumor type being treated and are associated with varying degrees of emetogenic potential. Since the distribution of risk factors for chemotherapy-induced nausea and vomiting differs across tumor types, it is important to understand the efficacy of antiemetic regimens in multiple patient populations. To characterize treatment response in patients with various malignancies (e.g., breast, gastrointestinal, genitourinary, and lung) treated with either highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) regimens, a pooled analysis of patient-level data from 4 large randomized trials was performed (N=2813). Patients receiving an antiemetic regimen containing aprepitant, ondansetron, and dexamethasone were compared with patients receiving an active-control antiemetic regimen containing ondansetron plus dexamethasone. In all tumor types analyzed, complete responses were observed in a higher proportion of HEC-treated patients receiving aprepitant compared with active-control patients (genitourinary [61.5% vs 40.6%, P<0.001], gastrointestinal [68.2% vs 44.7%, P=0.013], and lung cancers [73.5% vs 52.8%, P<0.001]). For MEC-treated patients, complete response rates were also higher for aprepitant patients than active-control patients for all tumor types, with a significant difference noted among patients with breast cancer (54.9% vs 43.9%, P<0.0001). The proportion of patients with no vomiting was higher in both HEC- and MEC-treated patients. While results of previous studies provide support for the use of antiemetic regimens that include aprepitant, a selective 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone, this analysis demonstrates the consistent efficacy of aprepitant as part of an antiemetic regimen across different tumor types and chemotherapy regimens., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: Data from two randomized trials, evaluating a single-day regimen of palonosetron plus dexamethasone against emesis due to moderately emetogenic chemotherapy, were assessed for the impact of age on outcome in a pooled sample of women receiving anthracycline and/or cyclophosphamide (AC)-containing chemotherapy., Methods: Chemo-naïve breast cancer patients randomized to receive palonosetron (0.25 mg) plus dexamethasone (8 mg IV) on day 1 of chemotherapy (n = 200), or the same regimen followed by oral dexamethasone (8 mg) on days 2 and 3 (n = 205), were included in the analysis. The primary endpoint was complete response (CR: no vomiting and no rescue anti-emetics) in the 5-day study period. The effect of the 1-day regimen and age (<50 and ≥ 50 years) was investigated by a meta-analysis of individual patient data., Results: Younger patients comprised 43 % and 49 % of the 1-day and 3-day regimen groups, respectively; 94 % of the pooled sample received the AC combination. There were no between-treatment differences in CR rate according to age during all observation periods. In the 1-day regimen group, 55.2 % of younger patients achieved overall CR compared with 54 % of older patients. In the 3-day regimen group, 51.5 % of younger patients achieved overall CR compared with 58.7 % of older patients. In the adjusted analysis, younger age was not associated with overall CR to treatment (risk difference, -3.1 %; 95 % CI, -13.0 to 6.7 %; P = 0.533)., Conclusions: These results provide evidence that, irrespective of age, the dexamethasone-sparing regimen is not associated with a significant loss in overall anti-emetic protection in women undergoing AC-containing chemotherapy.

Background: Various antiemetic agents are commonly administered during and after chemotherapy to prevent nausea and vomiting depending on the emetogenic risk. Data specific for patients older than 65 are rarely discussed and it is often assumed that such patients have less risk of nausea and vomiting and might not need the same prevention., Objective: To determine whether response to antiemetic regimens incorporating aprepitant varies with patient age, we combined previously unpublished subgroup analyses from four previously published studies., Methods: Risk ratios were combined using standard meta-analytic techniques to determine whether antiemetic regimens including aprepitant lead to more complete responses to antiemetic therapy than regimens without aprepitant, among patients aged 65 and over., Results: Patients aged 65 and over have a significantly greater chance of experiencing a complete response (no vomiting or use of rescue therapy) to antiemetic treatment when aprepitant is included in the antiemetic regimen (Risk Ratio 1.25, 95% Confidence Interval 1.11 to 1.40, p=0.0002) than when it is not. This risk ratio is not significantly different (Q=0.281, p=0.596) from the risk ratio calculated for patients under age 65 (1.30, 95% Confidence Interval 1.19 to 1.42), from the same set of studies., Limitations: This meta-analysis combines studies utilizing different antiemetic regimens and different patient populations. Only a single efficacy outcome is included, and safety is not assessed., Conclusion: We conclude that for both the under 65years and the age 65 and over populations, antiemetic regimens including aprepitant, along with a 5-HT3 antagonist and a corticosteroid, are more effective in reducing chemotherapy-induced nausea and vomiting than regimens that do not include aprepitant., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To determine the variable burden of disease of patients with advanced estrogen receptor-positive (ER+) breast cancer and assess the current treatment landscape after failure of first-line endocrine therapy., Methods: A comprehensive literature review was performed (2000-2011) by searching Medline via PubMed, and Embase and Cochrane databases, to assess disease burden (i.e. societal, humanistic, and/or economic burden) and treatment landscape for second-line therapy of ER+ advanced breast cancer in postmenopausal women., Results: Only 1 study was identified that evaluated burden of disease based on ER status (ER+, ER-negative, or ER-unknown); this study was a subgroup analysis assessing the impact of breast cancer recurrence over 10 years. The investigators reported that only minor differences in survival and medical costs were noted based on ER status in relapsing patients. Regardless of ER status, patients with breast cancer recurrence consumed more healthcare resources and were associated with more costly care than those without recurrence. A total of 7 studies were identified related to treatment outcomes of second-line therapy in ER+ patients. A combined international population totaled >3800 patients who had progressed on prior hormonal therapy, including tamoxifen and aromatase inhibitors. Three trials performed a comparative efficacy/safety assessment of an ER antagonist vs. aromatase inhibitor, 1 trial compared an aromatase inhibitor to megestrol acetate, and 1 trial compared 2 aromatase inhibitors. Among each of the studies evaluated, no significant differences were observed in the primary efficacy endpoint, and the safety profiles were similar. Two additional studies demonstrated a similar or better efficacy and safety profile based on different dosing evaluations., Conclusions: Currently, there is insufficient evidence on the economic and humanistic burden associated with ER status, and this gap warrants further research. With increasing drug resistance and greater economic burden associated with breast cancer recurrence, there is an unmet medical need for improved treatment in this patient population., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Until recently, prescribers had to deal with generics, considered to be simple molecules that are easy to copy. But as discussed in this paper, the biodisponibility of generics remains a source of uncertainty. And now there are biosimilars, limited for the time being in the cancer setting to granulocyte-colony stimulating factors (G-CSFs) and epoetins. Soon there will be biosimilar monoclonal antibodies with anticancer activity. Prescribers will ask, as they did for generics, if such drugs have the same activity as originators, if their safety profile is the same, if quality of the production process is guaranteed. Prescribers will want to know if their patients are indeed receiving the prescribed product, and not another. Finally prescribers will want to check that the lower cost of biosimilars will allow them to adhere to international guidelines. This should benefit patients and the community.

In women who develop bone metastases from breast cancer (BC), interactions between tumor cells and osteoclasts within the bone lead to localized bone destruction and increase the risk of skeletal-related events (SREs). Bisphosphonates inhibit osteoclast-mediated bone resorption, and have been used extensively for treating post-menopausal osteoporosis and reducing the risk of SREs in patients with bone metastases. A number of clinical trials in women with early stage BC have demonstrated that adding bisphosphonates to adjuvant endocrine therapy can prevent bone loss and may prevent disease recurrence and improve disease-free survival. In women with bone metastases from BC, bisphosphonates have demonstrated efficacy for reducing skeletal morbidity and pain and improving quality of life. Recent economic analyses have demonstrated that bisphosphonate therapy is a cost-effective use of healthcare resources. This review summarizes the available data for bisphosphonate benefits in both the adjuvant and metastatic settings in the context of evolving clinical practice., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Largely a disease of older men, prostate cancer is likely to become a growing burden in the developed world as the population ages and overall life expectancy increases. Furthermore, prostate cancer management in older men is not optimal, reflecting the lack of training dedicated to senior adults in fellowship programs and the lack of specific guidelines to manage senior adults. The International Society of Geriatric Oncology (SIOG) convened a multidisciplinary Prostate Cancer Working Group to review the evidence base and provide advice on the management of the disease in senior age groups. The Working Group reported that advancing age, by itself, is not a reliable guide to treatment decision making for men with either localized or advanced prostate cancer. Instead, the SIOG guidelines advise health care teams to assess the patient's underlying health status, which is largely dictated by associated comorbid conditions, but also by dependency in activities of daily living and nutritional status, and to use the findings to categorize the individual into one of four groups: healthy, vulnerable, frail, or terminally ill. The guidelines recommend that a patient categorized as healthy or vulnerable (i.e., with reversible problems following geriatric intervention) should receive the same approach to treatment as a younger patient. Frail patients should be managed using adapted treatment strategies, and the terminally ill should receive symptomatic/palliative care only. The guidelines may have ongoing relevance as the treatment options for prostate cancer expand.

The landscape of treatment for advanced prostate cancer is continually evolving as new therapies are developed and guidelines are constantly updated. However, the management of older men with advanced disease is not optimal. Many men are denied chemotherapy based on their chronological age, not their health status. Androgen-deprivation therapy (ADT) remains the mainstay of first-line treatment of advanced disease. Once the disease becomes resistant to castration, docetaxel-based chemotherapy is the regulatory-approved standard of care, irrespective of age. The place of weekly docetaxel in patients with poor performance status and signs of frailty has to be further evaluated in clinical studies. New treatments are now available, or on the horizon, for disease that progresses during or after docetaxel therapy. Cabazitaxel and abiraterone have been shown to prolong survival, irrespective of age, and are already in clinical use having received regulatory approval. The optimal sequence for these two agents is still unknown, although there is some indication that in patients predicted to be poor responders to abiraterone (high Gleason score, progression during docetaxel therapy, rapid progression to castrate-resistant prostate cancer with ADT) cabazitaxel should be the preferred choice. Further advances are being investigated, with promising data reported from phase III trials.

Background: Bone mineral density (BMD)-based guidelines for bone-directed therapy in women with early breast cancer (EBC) appear inadequate for averting fractures, particularly during aromatase inhibitor (AI) therapy. Therefore, an algorithm was developed to better assess risk and direct treatment (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407-1416). Here, we provide updated guidance on pharmacologic interventions to prevent/treat aromatase inhibitor-associated bone loss (AIBL)., Design: Systematic literature review identified recent advances in preventing/treating AIBL. Individual agents were assessed based on trial size, design, follow-up, and safety., Results: Fracture risk factors in patients with EBC remain unchanged (Hadji P, Body JJ, Aapro MS et al. Practical guidance for the management of aromatase inhibitor-associated bone loss. Ann Oncol 2008; 19: 1407-1416). The World Health Organization Fracture Risk Assessment Tool algorithm includes fracture risk factors plus BMD but does not adequately address AIBL effects. Several antiresorptives can prevent/treat AIBL. However, concerns regarding compliance and long-term efficacy/safety remain. Overall, evidence is strongest for twice-yearly zoledronic acid (ZOL), and recent advances support additional anticancer benefits from ZOL., Conclusions: All patients initiating AIs need advice regarding exercise, calcium/vitamin D supplements, baseline BMD monitoring (when available), and bone-directed therapy if T-score <-2.0 or at least two fracture risk factors were observed. Patients with T-score > -2.0 and no risk factors should be managed based on BMD loss during years 1-2. Unsatisfactory compliance/decreasing BMD after 12-24 months on oral bisphosphonates should trigger a switch to i.v. bisphosphonate.

Chemotherapy-induced neutropenia is a major risk factor for infection-related morbidity and mortality and also a significant dose-limiting toxicity in cancer treatment. Patients developing severe (grade 3/4) or febrile neutropenia (FN) during chemotherapy frequently receive dose reductions and/or delays to their chemotherapy. This may impact the success of treatment, particularly when treatment intent is either curative or to prolong survival. In Europe, prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs), such as filgrastim (including approved biosimilars), lenograstim or pegfilgrastim is available to reduce the risk of chemotherapy-induced neutropenia. However, the use of G-CSF prophylactic treatment varies widely in clinical practice, both in the timing of therapy and in the patients to whom it is offered. The need for generally applicable, European-focused guidelines led to the formation of a European Guidelines Working Party by the European Organisation for Research and Treatment of Cancer (EORTC) and the publication in 2006 of guidelines for the use of G-CSF in adult cancer patients at risk of chemotherapy-induced FN. A new systematic literature review has been undertaken to ensure that recommendations are current and provide guidance on clinical practice in Europe. We recommend that patient-related adverse risk factors, such as elderly age (≥65 years) and neutrophil count be evaluated in the overall assessment of FN risk before administering each cycle of chemotherapy. It is important that after a previous episode of FN, patients receive prophylactic administration of G-CSF in subsequent cycles. We provide an expanded list of common chemotherapy regimens considered to have a high (≥20%) or intermediate (10-20%) risk of FN. Prophylactic G-CSF continues to be recommended in patients receiving a chemotherapy regimen with high risk of FN. When using a chemotherapy regimen associated with FN in 10-20% of patients, particular attention should be given to patient-related risk factors that may increase the overall risk of FN. In situations where dose-dense or dose-intense chemotherapy strategies have survival benefits, prophylactic G-CSF support is recommended. Similarly, if reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis, primary G-CSF prophylaxis may be used to maintain chemotherapy. Clinical evidence shows that filgrastim, lenograstim and pegfilgrastim have clinical efficacy and we recommend the use of any of these agents to prevent FN and FN-related complications where indicated. Filgrastim biosimilars are also approved for use in Europe. While other forms of G-CSF, including biosimilars, are administered by a course of daily injections, pegfilgrastim allows once-per-cycle administration. Choice of formulation remains a matter for individual clinical judgement. Evidence from multiple low level studies derived from audit data and clinical practice suggests that some patients receive suboptimal daily G-CSFs; the use of pegfilgrastim may avoid this problem., (Copyright © 2010 Elsevier Ltd. All rights reserved.)