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Filgrastim is approved for several indications, including reduction of the incidence and duration of chemotherapy-induced neutropenia and for stem cell mobilization. The filgrastim biosimilar, EP2006, has been available in Europe since 2009, and in the United States since 2015. In this time, preclinical and clinical data used to support the approval of EP2006 have been published. These data established the biosimilarity of EP2006 to reference filgrastim in terms of structure, pharmacokinetics, pharmacodynamics, efficacy, safety, and immunogenicity. Additional real-world evidence studies have also demonstrated equivalent efficacy and safety of EP2006 compared with reference filgrastim, both in the reduction of neutropenia and in stem cell mobilization in clinical practice. This review summarizes these preclinical, clinical, and real-world data, as well as the available cost-effectiveness data, for EP2006 since its approval 15 years ago., Competing Interests: Declaration of Competing Interest PG has received honoraria for lectures and/or consulting from Amgen, Pfizer, and Sandoz. NH has received honoraria for lectures and/or consulting from AstraZeneca, Daiichi-Sankyo, Gilead, Lilly, MSD, Novartis, Pierre-Fabre, Pfizer, Roche, Sandoz, Sanofi, and Seagen. IB and SH are employees of Sandoz Group AG. BLR has received research grants and support from Gilead Sciences and Roche South Africa, and consulting/advisory fees from AstraZeneca, Gilead Sciences, Lilly, MSD, Novartis, OBI Pharma, and Roche South Africa . RA has no conflicts of interest to declare. MA has received honoraria for lectures and/or consulting from Amgen, Bayer Schering, BMS, Celgene, Cephalon, Chugai, Clinigen, Eisai, Genomic Health, GSK, G1 Therapeutics, Helsinn, Hospira, Ipsen, Johnson & Johnson, Kyowa Hakko Kirin, Lilly, Novartis, Merck, Merck Serono, Mundipharma, Novartis, OrthoBiotech, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Taiho, Tesaro, Teva, and Vifor., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The COVID-19 pandemic has affected healthcare systems globally, leading to reorganization of medical activities. We performed an international survey aimed to investigate the medium- and long-term impact on oncology units., Materials and Methods: An 82-item survey was distributed from June 17 to July 14, 2020 among medical oncologists worldwide., Results: One hundred nine medical oncologists from 18 countries in Europe (n = 93), United States (n = 5), and Latin America (n = 11) answered the survey. A systematic tracing of COVID-19-positive patients was continued in the postacute phase by 77.1% of the centers; 64.2% of the respondents participated in a local registry and 56% in international or national registries of infected patients. Treatment adaptations were introduced, and surgery was the most affected modality being delayed or canceled in more than 10% of patients in 34% of the centers, whereas early cessation of palliative treatment was reported in 32.1% of the centers; 64.2% of respondents reported paying attention to avoid undertreatments. The use of telemedicine has been largely increased. Similarly, virtual tools are increasingly used particularly for medical education and international or national or multidisciplinary meetings. 60.6% of the participants reduced clinical activity, and 28.4% compensated by increasing their research activity. Significant reduction of clinical trial activities is expected in 37% of centers this year. The well-being of healthcare staff would not recover by the end of the year according to 18% of the participants., Conclusion: The COVID-19 outbreak has had a major impact on oncologic activity, which will persist in the future, irrespective of geographical areas.

Background: COVID-19 appeared in late 2019, causing a pandemic spread. This led to a reorganisation of oncology care in order to reduce the risk of spreading infection between patients and healthcare staff. Here we analysed measures taken in major oncological units in Europe and the USA., Methods: A 46-item survey was sent by email to representatives of 30 oncological centres in 12 of the most affected countries. The survey inquired about preventive measures established to reduce virus spread, patient education and processes employed for risk reduction in each oncological unit., Results: Investigators from 21 centres in 10 countries answered the survey between 10 April and 6 May 2020. A triage for patients with cancer before hospital or clinic visits was conducted by 90.5% of centres before consultations, 95.2% before day care admissions and in 100% of the cases before overnight hospitalisation by means of phone calls, interactive online platforms, swab test and/or chest CT scan. Permission for caregivers to attend clinic visits was limited in many centres, with some exceptions (ie, for non-autonomous patients, in the case of a new diagnosis, when bad news was expected and for terminally ill patients). With a variable delay period, the use of personal protective equipment was unanimously mandatory, and in many centres, only targeted clinical and instrumental examinations were performed. Telemedicine was implemented in 76.2% of the centres. Separated pathways for COVID-19-positive and COVID-19-negative patients were organised, with separate inpatient units and day care areas. Self-isolation was required for COVID-19-positive or symptomatic staff, while return to work policies required a negative swab test in 76.2% of the centres., Conclusion: Many pragmatic measures have been quickly implemented to deal with the health emergency linked to COVID-19, although the relative efficacy of each intervention should be further analysed in large observational studies., Competing Interests: Competing interests: HSR reported fundings to the Institution from Eisai, Genentech, Lilly, Macrogenics, Merk, Novartis, OBI Pharma, Odonate Therapeutics, Immunomedics, Daiichi-Sankyo and Pfizer; travel fees from Pfizer, Novartis, MacroGenics, Mylan, Daiichi-Sankyo and AstraZeneca; consulting roles for Samsung and Celtrion. MM reported personal fees from Roche, Novartis, Puma, AstraZeneca, Amgen, Taiho Oncology, Daiichi-Sankyo, PharmaMar, Eli-Lilly and Pfizer; grants from Roche, Novartis and Puma. MC reported a grant from Pfizer; personal fees from CytoDyn, Pfizer, Eli-Lilly, Novartis, Foundation Medicine, G1 Therapeutics, Sermionex and Genentech. JC reported funding to the institution from 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 and Queen Mary University of London; honoraria from Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Eli-Lilly, Merck Sharp & Dohme, and Daiichi Sankyo; travel fees from Roche, Novartis, Eisai, Pfizer, Daiichi Sankyo; consulting/advisor role for Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi-Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology and Boehringer Ingelheim; stock, patents and intellectual property of MedSIR. SAH reported grants from Ambrx, Amgen, Arvinas, Bayer, Daiichi-Sankyo, Genentech/Roche, GSK, Immunomedics, Eli-Lilly, Macrogenics, Novartis, Pfizer, OBI Pharma, Pieris, Puma, Radius, Sanofi, Seattle Genetics and Dignitana; travel fees from Lilly and Novartis; stock options from NK Max; editorial support from Roche/Genetech, Eli-Lilly and Pfizer. MT declares travel, accomodations, expenses by Roche, Bristol-Myers Squibb, Astra Zeneca, Takeda; activity as medical writer supported by Novartis and Amgen, outside the present work. MC reported funding to the institution from Sanofi, Pierre-Fabre, AstraZeneca, Servier, Novartis, Abbvie, Accord and Pfizer; personal fees from GT1, Sanofi, Pierre-Fabre, AstraZeneca, Servier, Novartis, Abbvie, Accord and Pfizer. RB reported personal fees from Accord, AstraZeneca, Daiichi-Sankyo, Eisai, Eli-Lilly, MSD, Novartis, Roche, Puma, Pierre-Fabre and Sandoz; grants from Daiichi-Sankyo, Novartis and Roche; non-financial support from Eli-Lilly and MSD. SDP reported personal fees from Roche, Novartis, Pfizer, Celgene, AstraZeneca and Eli-Lilly. VM reported funding to the institution from Novartis, Roche, Seattle Genetics and Genentech; personal fees from Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, Pfizer, MSD, Novartis, Roche, Teva and Seattle Genetics; consultancy honoraria from Genomic Health, Hexal, Roche, Pierre-Fabre, Amgen, ClinSol, Novartis, MSD, Daiichi-Sankyo, Eisai, Eli-Lilly, Tesaro, Seattle Genetics and Nektar. J-PM reported personal fees from Roche, AstraZeneca, Bayer, Innate, Merck-Serono, Boeringher, BMS, Novartis, Janssen, Incyte, Cue Biopharma, ALX Oncology and Pfizer; grant from BMS; travel fee from Amgen; other support from MSD, Psioxus, Debio and Nanobiotix. GJ reported personal fees from Novartis, Roche, Pfizer, Eli-Lilly, Amgen, BMS, AstraZeneca, Daiichi-Sankyo and Abbvie; grants from Novartis, Roche and Pfizer; non-financial support from Medimmune and Merck KGaA., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: HER2-targeted treatments have improved outcomes in patients with HER2-positive breast cancer in the neoadjuvant, adjuvant, and metastatic settings; however, some patients remain at risk of relapse or death for many years after treatment of early-stage disease. Therefore, new strategies are needed. We did a phase 3 trial to assess a neoadjuvant regimen for HER2-positive breast cancer that replaces traditional systemic chemotherapy with targeted treatment., Methods: We did a randomised, open-label phase 3 KRISTINE trial in 68 Translational Research In Oncology centres (hospitals and specialty cancer centres in Asia, Europe, USA, and Canada). Eligible participants were aged 18 years or older with centrally confirmed HER2-positive stage II-III operable breast cancer (>2 cm tumour size), an Eastern Cooperative Oncology Group performance status of 0-1, and a baseline left ventricular ejection fraction of at least 55% (by echocardiogram or multiple-gated acquisition scan). We randomly assigned participants (1:1) to receive either trastuzumab emtansine plus pertuzumab or docetaxel, carboplatin, and trastuzumab plus pertuzumab. We did the randomisation via an interactive response system under a permuted block randomisation scheme (block size of four), stratified by hormone receptor status, stage at diagnosis, and geographical location. Patients received six cycles (every 3 weeks) of neoadjuvant trastuzumab emtansine plus pertuzumab (trastuzumab emtansine 3·6 mg/kg; pertuzumab 840 mg loading dose, 420 mg maintenance doses) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (docetaxel 75 mg/m 2 ; carboplatin area under the concentration-time curve 6 mg/mL × min; trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance doses) plus pertuzumab [same dosing as in the other group]). All treatments were administered intravenously. The primary objective was to compare the number of patients who achieved a pathological complete response (ypT0/is, ypN0), between groups in the intention-to-treat population (two-sided assessment), based on local evaluation of tumour samples taken at breast cancer surgery done between 14 days and 6 weeks after completion of neoadjuvant therapy. Safety was analysed in patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02131064, and follow-up of the adjuvant phase is ongoing., Findings: Between June 25, 2014, and June 15, 2015, we randomly assigned 444 patients to neoadjuvant treatment with trastuzumab emtansine plus pertuzumab (n=223) or docetaxel, carboplatin, and trastuzumab plus pertuzumab (n=221). A pathological complete response was achieved by 99 (44·4%) of 223 patients in the trastuzumab emtansine plus pertuzumab group and 123 (55·7%) of 221 patients in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group (absolute difference -11·3 percentage points, 95% CI -20·5 to -2·0; p=0·016). During neoadjuvant treatment, compared with patients receiving docetaxel, carboplatin, and trastuzumab plus pertuzumab, fewer patients receiving trastuzumab emtansine plus pertuzumab had a grade 3-4 adverse event (29 [13%] of 223 vs 141 [64%] of 219) or a serious adverse event (11 [5%] of 223 vs 63 [29%] of 219). The most common grade 3-4 adverse events in the trastuzumab emtansine plus pertuzumab group were decreased platelet count (three [1%] of 223 patients vs 11 [5%] of 219 with docetaxel, carboplatin, and trastuzumab plus pertuzumab), fatigue (three [1%] vs seven [3%]), alanine aminotransferase increase (three [1%] vs four [2%]), and hypokalaemia (three [1%] vs five [2%]). The most common grade 3-4 adverse events in the docetaxel, carboplatin, and trastuzumab plus pertuzumab group were neutropenia (55 [25%] of 219 vs one [<1%] of 223 with trastuzumab emtansine plus pertuzumab), diarrhoea (33 [15%] vs 2 [<1%]), and febrile neutropenia (33 [15%] vs 0). No deaths were reported during neoadjuvant treatment., Interpretation: Traditional neoadjuvant systemic chemotherapy plus dual HER2-targeted blockade (docetaxel, carboplatin, and trastuzumab plus pertuzumab) resulted in significantly more patients achieving a pathological complete response than HER2-targeted chemotherapy plus HER2-targeted blockade (trastuzumab emtansine plus pertuzumab); however, numerically more grade 3-4 and serious adverse events occurred in the chemotherapy plus trastuzumab and pertuzumab group. Further efforts to improve the efficacy of chemotherapy without imparting more toxicity are warranted., Funding: F Hoffmann-La Roche and Genentech., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Recommendations for specimen collection and handling have been developed for adoption across breast cancer clinical trials conducted by the Breast International Group (BIG)-sponsored Groups and the National Cancer Institute (NCI)-sponsored North American Cooperative Groups. These recommendations are meant to promote identifiable standards for specimen collection and handling within and across breast cancer trials, such that the variability in collection/handling practices that currently exists is minimized and specimen condition and quality are enhanced, thereby maximizing results from specimen-based diagnostic testing and research. Three working groups were formed from the Cooperative Group Banking Committee, BIG groups, and North American breast cancer cooperative groups to identify standards for collection and handling of (1) formalin-fixed, paraffin-embedded (FFPE) tissue; (2) blood and its components; and (3) fresh/frozen tissue from breast cancer trials. The working groups collected standard operating procedures from multiple group specimen banks, administered a survey on banking practices to those banks, and engaged in a series of discussions from 2005 to 2007. Their contributions were synthesized into this document, which focuses primarily on collection and handling of specimens to the point of shipment to the central bank, although also offers some guidance to central banks. Major recommendations include submission of an FFPE block, whole blood, and serial serum or plasma from breast cancer clinical trials, and use of one fixative and buffer type (10% neutral phosphate-buffered formalin, pH 7) for FFPE tissue across trials. Recommendations for proper handling and shipping were developed for blood, serum, plasma, FFPE, and fresh/frozen tissue.