Publications by authors named "Alexandru Eniu"

54 Publications

Live European School of Oncology e-Sessions (e-ESO).

Crit Rev Oncol Hematol 2021 Mar 16:103301. Epub 2021 Mar 16.

European School of Oncology, Milan, Italy.

The European School of Oncology (ESO) embarked on an online educational project, starting with live sessions in 2008 (e-ESO). Our scholars and young oncologists identified the need to be offered independent high-level online education with contributions from experts around the world, free of charge and available at any moment. We report on various types of e-sessions, such as grand-rounds, highlights, debates, clinical cases and other sessions. Our audience has grown over the last decade, reaching 11,123 users who have viewed a total of 77,041 sessions since the beginning of 2008. Moreover, our activities on social media platforms have enhanced our visibility, reaching more physicians around the globe. Due to the recent events surrounding the COVID-19 pandemic, online education has proven to be of great value in offering long-distance teaching. We have analyzed the growth of our audience and its attendance over the last 12 years.
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http://dx.doi.org/10.1016/j.critrevonc.2021.103301DOI Listing
March 2021

Why is appropriate healthcare inaccessible for many European breast cancer patients? - The EBCC 12 manifesto.

Breast 2021 Feb 2;55:128-135. Epub 2021 Jan 2.

Iridium Kankernetwerk and University of Antwerp, Wilrijk, Antwerp, Belgium. Electronic address:

In Europe, inappropriate reimbursement and funding rules and regulations act as disincentives to best breast cancer care or, at worst, hinder best care. This problem was the focus of the 12th European Breast Cancer Conference (EBCC) manifesto, discussed during the virtual conference. As patient involvement is indispensable in driving changes to clinical practice, Europa Donna the European patient advocacy group was closely involved in the 12th manifesto. Reimbursement policies have rarely evolved with advances in breast cancer care such as outpatient (ambulatory) care rather than inpatient admission, use of oral or subcutaneous anti-cancer drugs rather than day-hospital intravenous administration, oncoplastic surgery techniques to minimize mastectomy rates, breast reconstructive surgery, risk-reducing surgery for BRCA mutation carriers, or use of hypo-fractionated breast radiation therapy. Although each European country, region and centre will have to understand how their reimbursement policies may hinder best care and find their own solutions, the problems are similar throughout Europe and some solutions can be broadly applied. This manifesto is not calling for more funding or demanding changes that will result in more expensive care. Reimbursement, if better aligned with guidelines and optimal clinical practice, will deliver more cost-effective healthcare. This will release resources, support more equitable use of finite funding and resources, so allowing more European breast cancer patients to benefit from evidence-based treatment recommended by national and international guidelines.
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http://dx.doi.org/10.1016/j.breast.2020.12.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817501PMC
February 2021

Recommendations from the ASCO Academic Global Oncology Task Force.

JCO Glob Oncol 2020 10;6:1666-1673

American Society of Clinical Oncology, Alexandria, VA.

In recognition of the rising incidence and mortality of cancer in low- and middle-resource settings, as well as the increasingly international profile of its membership, ASCO has prioritized efforts to enhance its engagement at a global level. Among the recommendations included in the 2016 Global Oncology Leadership Task Force report to the ASCO Board of Directors was that ASCO should promote the recognition of global oncology as an academic field. The report suggested that ASCO could serve a role in transitioning global oncology from an informal field of largely voluntary activities to a more formal discipline with strong research and well-defined training components. As a result of this recommendation, in 2017, ASCO formed the Academic Global Oncology Task Force (AGOTF) to guide ASCO's contributions toward formalizing the field of global oncology. The AGOTF was asked to collect and analyze key issues and barriers toward the recognition of global oncology as an academic discipline, with an emphasis on training, research, and career pathways, and produce a set of recommendations for ASCO action. The outcome of the AGOTF was the development of recommendations designed to advance the status of global oncology as an academic discipline.
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http://dx.doi.org/10.1200/GO.20.00497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713550PMC
October 2020

The global landscape of drug development for kidney cancer.

Cancer Treat Rev 2020 Sep 23;89:102061. Epub 2020 Jun 23.

Englander Institute for Precision Medicine, Weill Cornell Medicine, Hematology/Oncology, New York, NY USA. Electronic address:

Renal cell cancer (RCC) is the third most diagnosed genitourinary malignancy in the world. Nearly a half of the diagnoses and 60% of related deaths occur in low-middle income countries (LMs), where prognosis is generally poor. We conducted a systematic research of ClinicalTrials.gov, searching RCC ongoing studies for adult patients. We included 205 trials in the final analysis. The enrolling centers were mainly distributed in high-income settings (88.9%). We estimated 94.6% of the trial population was enrolled in only five countries and none in LMs. Clinical drug development for RCC is driven by early phase studies, mainly assessing small molecule tyrosine kinase inhibitors and immunotherapy or the combination. Sixty percent of the trials were industry sponsored. Only a minority of the trials were in the early setting of care, adjuvant or neoadjuvant therapy. Disparities in drug development in LMs mirror a common underestimation of the value of research among the national priorities in cancer health planning, resulting in poor ethnic diversity and inclusiveness. This commonly results in incomplete knowledge of activity and safety of medicines across different ethnic groups, with consequences on priorities for cancer interventions and estimates of benefit in LMs patients. The use of RCC as a case study for inclusiveness suggests poor inclusion of non- Caucasian populations in the trials, especially trials testing new immunotherapy and targeted agents where RCC drug development is more pronounced, resulting in issues of generalizability in other ethnic groups when these compounds are approved with no ethnic restrictions or specifications.
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http://dx.doi.org/10.1016/j.ctrv.2020.102061DOI Listing
September 2020

The Breast Health Global Initiative 2018 Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation: Methods and overview.

Cancer 2020 05;126 Suppl 10:2339-2352

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice.

Methods: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening.

Results: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits.

Conclusions: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.
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http://dx.doi.org/10.1002/cncr.32891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482869PMC
May 2020

Breast cancer treatment: A phased approach to implementation.

Cancer 2020 05;126 Suppl 10:2365-2378

Hopital Riviera Chablais, Vaud-Valais, Rennaz, Switzerland.

Optimal treatment outcomes for breast cancer are dependent on a timely diagnosis followed by an organized, multidisciplinary approach to care. However, in many low- and middle-income countries, effective care management pathways can be difficult to follow because of financial constraints, a lack of resources, an insufficiently trained workforce, and/or poor infrastructure. On the basis of prior work by the Breast Health Global Initiative, this article proposes a phased implementation strategy for developing sustainable approaches to enhancing patient care in limited-resource settings by creating roadmaps that are individualized and adapted to the baseline environment. This strategy proposes that, after a situational analysis, implementation phases begin with bolstering palliative care capacity, especially in settings where a late-stage diagnosis is common. This is followed by strengthening the patient pathway, with consideration given to a dynamic balance between centralization of services into centers of excellence to achieve better quality and decentralization of services to increase patient access. The use of resource checklists ensures that comprehensive therapy or palliative care can be delivered safely and effectively. Episodic or continuous monitoring with established process and quality metrics facilitates ongoing assessment, which should drive continual process improvements. A series of case studies provides a snapshot of country experiences with enhancing patient care, including the implementation of national cancer control plans in Kenya, palliative care in Romania, the introduction of a 1-stop clinic for diagnosis in Brazil, the surgical management of breast cancer in India, and the establishment of a women's cancer center in Ghana.
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http://dx.doi.org/10.1002/cncr.32910DOI Listing
May 2020

Enhancing global access to cancer medicines.

CA Cancer J Clin 2020 03 18;70(2):105-124. Epub 2020 Feb 18.

Preclinical Research Program, Vall d'Hebron Institute of Oncology, Barcelona, Spain.

Globally, cancer is the second leading cause of death, with numbers greatly exceeding those for human immunodeficiency virus/acquired immunodeficiency syndrome, tuberculosis, and malaria combined. Limited access to timely diagnosis, to affordable, effective treatment, and to high-quality care are just some of the factors that lead to disparities in cancer survival between countries and within countries. In this article, the authors consider various factors that prevent access to cancer medicines (particularly access to essential cancer medicines). Even if an essential cancer medicine is included on a national medicines list, cost might preclude its use, it might be prescribed or used inappropriately, weak infrastructure might prevent it being accessed by those who could benefit, or quality might not be guaranteed. Potential strategies to address the access problems are discussed, including universal health coverage for essential cancer medicines, fairer methods for pricing cancer medicines, reducing development costs, optimizing regulation, and improving reliability in the global supply chain. Optimizing schedules for cancer therapy could reduce not only costs, but also adverse events, and improve access. More and better biomarkers are required to target patients who are most likely to benefit from cancer medicines. The optimum use of cancer medicines depends on the effective delivery of several services allied to oncology (including laboratory, imaging, surgery, and radiotherapy). Investment is necessary in all aspects of cancer care, from these supportive services to technologies, and the training of health care workers and other staff.
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http://dx.doi.org/10.3322/caac.21597DOI Listing
March 2020

Breast Cancer: Reimbursement Policies and Adoption of New Therapeutic Agents by National Health Systems.

Breast Care (Basel) 2019 Dec 24;14(6):373-381. Epub 2019 Sep 24.

Department of Breast Tumours, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania.

Background: Breast cancer is a cause of morbidity for more than half a million of patients in Europe, resulting in broad societal impacts that affect patients, families, and societies from a human, emotional, economic, and financial perspective. Expenditure for cancer medicines represents one of the principal driving costs of healthcare. The aim of this review is to describe the European policy and regulatory landscape of innovation uptake in breast oncology - with emphasis on value in cancer healthcare.

Summary: In Europe, several reimbursement models or policy tools have been developed by countries to compose their benefit packages. The most commonly applied scheme is the product-specific eligibility model, prioritizing selected medicines and their indications. Mixed models are commonly developed, addressing the protection of more vulnerable people, ensuring protection from impoverishment caused by cancer and containing disparities. However, the risk to incur significant out-of-pocket expenses for essential or newer medicines for cancer is still substantial in Europe, especially in low- and middle-income countries, determining greater financial distress and poorer outcome for patients. Value-based priority setting is an essential mechanism to ensure timely access to the most valuable medicines for breast cancer patients. Estimations of the value of medicines can be provided within health technology assessment services and networks and informed by benefit scales and tools.

Key Messages: There is ample room for reciprocal support across the diverse cultural and legal realities in Europe. The aim is common: save cancer patients from premature death by ensuring the timely access to the best care, protecting from financial hardships and distress to leave no cancer patient behind in poverty. Steps are to be taken to promote value-based priority setting, paving the way toward universal health coverage in Europe, where health of people is protected, and affordable best quality care is the only standard pursued and acceptable.
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http://dx.doi.org/10.1159/000502637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6940432PMC
December 2019

ESO-ESMO Masterclass in Clinical Oncology: Analysis and Evaluation of the Learning Self-Assessment Test.

J Cancer Educ 2021 Jun;36(3):556-560

European School of Oncology, Milan, Italy.

Masterclass in Clinical Oncology (MCO) represents the "key educational event" of European School of Oncology's (ESO) teaching program. MCO in collaboration with European Society for Medical Oncology (ESMO) is a multidisciplinary and clinical oriented educational event offered mainly to young oncologists worldwide. It provides full immersion in oncology with clinical case presentations and a Learning Self-Assessment Test (LSAT).LSAT is consisting of 45 multiple choice questions on an electronic platform referring to the material taught during the MCO. Three questions related to their topics are requested in advance from each faculty member. The major intentions of LSAT are the following: (a) the learning reflection of the massive information given during 4-5 days of intensive teaching and (b) to offer the opportunity to the participants to prepare themselves for their National Boards or for ESMO examination.In this article, we are analyzing and evaluating the results of LSAT from the ESO-ESMO Central European MCOs. We used the information of Central European MCOs for analysis due to the homogeneity of the available data. We assessed the level of participants' knowledge in relation to their oncology specialty or to their country of origin and the level of the quality of faculty teaching.
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http://dx.doi.org/10.1007/s13187-019-01664-6DOI Listing
June 2021

Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?

ESMO Open 2019 17;4(4):e000483. Epub 2019 Jul 17.

Department of Haematology and Oncology, University of Milano, Milan, Italy.

This review article is an overview of the session at the European Society for Medical Oncology (ESMO) Asia 2018 Congress entitled: 'Cancer medicines in Asia and Asia-Pacific: What is available, and is it effective enough?'. The article provides an overview of the session speakers' views on the impact that the lack of accessibility and availability of medicines has on patient outcomes in the treatment of breast cancer, colorectal cancer and lung cancer, responsible for more than one-third of cancer deaths in the Asian region. It also lists the various global policy initiatives that ESMO supports to promote the best cancer care in the Asian and Asia-Pacific region. The review presents extrapolated data from the 'ESMO International Consortium Study on the availability, out-of-pocket costs and accessibility of antineoplastic medicines in countries outside of Europe', which reveals several disparities among Asian countries, across the different income levels. In low- and middle-income countries, some barriers to the accessibility of anticancer medicines include the lack of government reimbursement, budget allocation for healthcare and quality-assured generic and biosimilar medicines, as well as shortages and patent rights. Throughout the article, the session presenters provide their views on strategies that can be considered to overcome these barriers.
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http://dx.doi.org/10.1136/esmoopen-2018-000483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6677966PMC
July 2019

Mapping cancer research across Central and Eastern Europe, the Russian Federation and Central Asia: Implications for future national cancer control planning.

Eur J Cancer 2018 11 20;104:127-136. Epub 2018 Oct 20.

Institute of Cancer Policy, Cancer Epidemiology, Population & Global Health, School of Cancer Sciences, King's College London & Guy's & St.Thomas' NHS Trust, London, UK. Electronic address:

Cancer research is an essential part of national cancer control programmes, and the emerging economies of Central and Eastern Europe (CEE) and the Russian Federation and Central Asia (R-CA) (Commonwealth of Independent States) remain relatively understudied. Here, we map the cancer research activity from the 29 countries across these regions over a 10-year period (2007-2016), using a standard scientometric approach. Research activity was compared with the countries' wealth and with the disease burden from different cancers, and analyses were also performed by the research domain (e.g. fundamental cancer biology, surgery). We found that although there was a correlation between outputs and national wealth, there were many outliers; the CEE countries publishing relatively more, and the R-CA, less. Outputs reflected cancer burdens, but there was a relative paucity of research on lung, colorectal, gastric and pancreatic cancer, as well as research domains such as screening and palliative care. Clinical trials accounted for only 3% of all research outputs from all countries, and were very international, with on average 1.5 CEE countries and 8.0 others involved in each article, and they were heavily cited (on average, 84 times in 5 years). Poland was by far the most research-active country, but significant needs and opportunities have been identified to expand the cancer research activity in all CEE and R-CA countries to enhance national cancer control planning.
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http://dx.doi.org/10.1016/j.ejca.2018.08.024DOI Listing
November 2018

Aberrant miRNAs expressed in HER-2 negative breast cancers patient.

J Exp Clin Cancer Res 2018 Oct 20;37(1):257. Epub 2018 Oct 20.

Research Center for Functional Genomics, Biomedicine and Translational Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.

Background: Breast cancer is a highly heterogeneous pathology, exhibiting a number of subtypes commonly associated with a poor outcome. Due to their high stability, microRNAs are often regarded as non-invasive cancer biomarkers, having an expression pattern specific for their 'cell of origin'.

Method: Triple negative breast cancer (TNBC: ER-, PR-, Her-2-) and double positive breast cancer (DPBC: ER+, PR+, Her-2) miRNA expression patterns were obtained by analysis of the TCGA (The Cancer Genome Atlas) data, followed by PCR-array analysis on plasma samples from 20 TNBC patients, 14 DPBC patients and 11 controls.

Results: Three downregulated and nine upregulated miRNAs were obtained from the TNBC analysis. Five overexpressed miRNAs were identified in the DPBC group. Four of the dysregulated miRNAs (miR-10a, miR-125b, miR-210 and miR-489) were common for both groups. The cluster miR-17-92 (miR-17, miR-20a, miR-20b, and miR-93), along with miR-130, miR-22 and miR-29a/c, were found to differentiate between TNBC and DPBC. A panel of five transcripts (miR-10a, miR-125, miR-193b, miR-200b and miR-489) was validated in a new set of plasma samples. The overlapping of TCGA and plasma profiling data revealed miR-200b, miR-200c, miR-210 and miR-29c as common signature. MiR-200b was validated on additional normal and tumor tissue samples. The expression level of this transcript from the TCGA data was correlated with lung and bone metastatic genes.

Conclusion: The miR-200b presents a great potential for the future advancements in the diagnostic/prognostic and therapeutic approach of TNBC, along with other coding or non-coding transcripts. However, this needs to be further integrated in a regulatory network that acts in conjunction with other markers that affect the patients' prognosis or response to therapy.
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http://dx.doi.org/10.1186/s13046-018-0920-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6196003PMC
October 2018

Facing the Global Challenges of Access to Cancer Medication.

J Glob Oncol 2018 09;4:1-7

Abdul Raman Jazieh and Abdulaziz H. Al-Saggabi, National Guard Health Affairs, Riyadh, Saudi Arabia; Mark McClung, Amgen Oncology, Thousand Oaks, CA; Robert Carlson, National Comprehensive Cancer Network, Fort Washington, PA; Lowell E. Schnipper, Beth Israel Deaconess Medical Center; Barri Blauvelt, University of Massachusetts, Boston, MA; Alexandru Eniu, Cancer Institute "Ion Chiricuta", Cluj-Napoca, Romania; Yousuf Zafar, Duke Cancer Institute, Durham, NC; and David Kerr, Oxford University, Oxford, United Kingdom.

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http://dx.doi.org/10.1200/JGO.17.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223443PMC
September 2018

Expenditures on Oncology Drugs and Cancer Mortality-to-Incidence Ratio in Central and Eastern Europe.

Oncologist 2019 01 4;24(1):e30-e37. Epub 2018 Sep 4.

Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

Background: There is a steady decline in cancer mortality in Western Europe (WE), but this trend is not so obvious in Central and Eastern Europe (CEE). One of the largest discrepancies between WE and CEE is the level of investment in cancer care. The objective of our analysis was to examine the correlation between mortality-to-incidence (M/I) ratio and expenditures on oncology drugs in CEE and WE.

Materials And Methods: This cross-sectional analysis was done on publicly available data. Data on expenditures for oncology drugs were obtained from QuintilesIMS, and data on M/I ratio from Globocan. The main outcome was mortality-to-incidence ratio, and the primary analysis was performed by Spearman's rank correlation.

Results: There is a large discrepancy in expenditure on oncology drugs per cancer case between WE and CEE, and within CEE. Average expenditure on oncology drugs per capita as well as per new cancer case was 2.5 times higher in WE than in CEE. Availability of oncology drugs was highest in Germany (100%), relatively similar in WE (average of 91%), but in CEE it ranged from 37% to 86%, with an average of 70%. Annual expenditures on all oncology drugs per new cancer case was significantly negatively correlated with the M/I ratio (Spearman's ρ = -0.90, < .001).

Conclusion: There is a financial threshold for oncology drugs per cancer case needed to increase survival. Based on significantly lower expenditures for oncology drugs in CEE in comparison with WE, more investment for drugs as well as better, more organized, value- oriented consumption is needed.

Implications For Practice: Cancer is not treated equally successfully in Western Europe (WE) and in Central and Eastern Europe (CEE). This study showed that success in treatment of cancer is associated with the amount of money invested in oncology drugs. CEE countries spend on average 2.5 times less than WE countries for oncology drugs per new cancer case. These findings should be used by health care providers and oncologists struggling for more resources and better, more organized, evidence-based allocation of these resources as well as better oncology outcomes.
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http://dx.doi.org/10.1634/theoncologist.2018-0093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324644PMC
January 2019

PARP Inhibitors in Breast Cancer: Why, How, and When?

Breast Care (Basel) 2018 Jul 20;13(3):216-219. Epub 2018 Jun 20.

Breast Cancer Unit, American Hospital of Paris, Neuilly-sur-Seine, France.

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http://dx.doi.org/10.1159/000490746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6062717PMC
July 2018

Global cancer control: responding to the growing burden, rising costs and inequalities in access.

ESMO Open 2018 2;3(2):e000285. Epub 2018 Feb 2.

Cancer Control, Management of Noncommunicable Diseases Unit Department for Management of Noncommunicable Diseases, Disability, Violence and Injury Prevention (NVI), World Health Organization, Geneva, Switzerland.

The cancer burden is rising globally, exerting significant strain on populations and health systems at all income levels. In May 2017, world governments made a commitment to further invest in cancer control as a public health priority, passing the World Health Assembly Resolution 70.12 on cancer prevention and control within an integrated approach. In this manuscript, the 2016 European Society for Medical Oncology Leadership Generation Programme participants propose a strategic framework that is in line with the 2017 WHO Cancer Resolution and consistent with the principle of universal health coverage, which ensures access to optimal cancer care for all people because health is a basic human right. The time for action is now to reduce barriers and provide the highest possible quality cancer care to everyone regardless of circumstance, precondition or geographic location. The national actions and the policy recommendations in this paper set forth the vision of its authors for the future of global cancer control at the national level, where the WHO Cancer Resolution must be implemented if we are to reduce the cancer burden, avoid unnecessary suffering and save as many lives as possible.
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http://dx.doi.org/10.1136/esmoopen-2017-000285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812392PMC
February 2018

Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer.

Eur J Cancer 2018 01 8;89:27-35. Epub 2017 Dec 8.

Ramón y Cajal University Hospital, Madrid and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.

Background: We report long-term efficacy and cardiac safety outcomes in patients with HER2-positive early breast cancer treated with neoadjuvant pertuzumab plus trastuzumab with anthracycline-containing or anthracycline-free chemotherapy.

Methods: Descriptive efficacy analyses were conducted in patients randomised to group A (cycles 1-6: trastuzumab [8 mg/kg loading dose and 6 mg/kg maintenance] plus pertuzumab [840 mg loading dose and 420 mg maintenance], plus 5-fluorouracil, epirubicin and cyclophosphamide [FEC] [cycles 1-3; 500 mg/m 5-fluorouracil/100 mg/m epirubicin/600 mg/m cyclophosphamide] then docetaxel [cycles 4-6; 75 mg/m, escalated to 100 mg/m if well tolerated]), B (cycles 1-3: FEC, cycles 4-6: trastuzumab plus pertuzumab plus docetaxel as mentioned previously) or C (cycles 1-6: trastuzumab plus pertuzumab plus docetaxel [75 mg/m, without dose escalation], and carboplatin [AUC 6]), five years after randomisation of the last patient. This study is registered with ClinicalTrials.gov, number NCT00976989.

Results: Three-year Kaplan-Meier survival estimates for disease-free survival (DFS) were 87% (95% confidence interval: 79-95), 88% (80-96) and 90% (82-97) in groups A-C, respectively. Progression-free survival (PFS) rates were 89% (81-96), 89% (81-96) and 87% (80-95). DFS hazard ratio for total pathological complete response (tpCR) versus no tpCR was 0.27 (0.11-0.64). During post-treatment follow-up, 2/72 (2.8%), 3/75 (4.0%) and 4/76 (5.4%) patients in groups A-C had any-grade left ventricular systolic dysfunction; eight (11.1%), 12 (16.0%) and nine (11.8%) patients experienced left ventricular ejection fraction declines ≥10% from baseline to <50%.

Conclusions: Long-term DFS and PFS were similar between groups. Patients who achieved tpCR had improved DFS. No new safety signals were identified.
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http://dx.doi.org/10.1016/j.ejca.2017.10.021DOI Listing
January 2018

Biosimilars: a position paper of the European Society for Medical Oncology, with particular reference to oncology prescribers.

ESMO Open 2016 16;1(6):e000142. Epub 2017 Jan 16.

Second University of Naples.

Biosimilars present a necessary and timely opportunity for physicians, patients and healthcare systems. If suitably developed clinically, manufactured to the correct standards and used appropriately, they can positively impact on the financial sustainability of healthcare systems. A critical consideration regarding the introduction of biosimilars into the clinic centres on the required information concerning all the respective procedures. This position paper aims to describe the issues revolving around biosimilars that are relevant to the field of oncology, especially the prescribers. More specifically, we discuss aspects related to definition, forms of biosimilars, labelling, extrapolation, interchangeability, switching, automatic substitution, clinical standards on safety and efficacy, responsibilities among prescribers and pharmacists, potential impact on financial burden in healthcare and the current scenario and future prospects of biosimilars in Europe and the rest of the world.
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http://dx.doi.org/10.1136/esmoopen-2016-000142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419210PMC
January 2017

Extended Adjuvant Chemotherapy in Triple-Negative Breast Cancer.

Breast Care (Basel) 2017 Jul 27;12(3):152-158. Epub 2017 Jun 27.

Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania.

Triple-negative breast cancer (TNBC) represents a heterogeneous breast cancer subtype with a poor prognosis. The optimal adjuvant chemotherapy regimen is still unknown. Although numerous large randomized trials have established the benefit of adjuvant anthracyclines and/or taxanes in TNBC, there is no preferred regimen for these patients. There is currently no guideline. Moreover, without knowing the optimal treatment backbone, it will not be possible to evaluate whether adding agents such as platinum or other novel therapies is beneficial for TNBC patients. Furthermore, the best duration of adjuvant treatment in TNBC is still unknown. This review will focus on results of clinical trials that analyzed the benefits of extending the duration of adjuvant treatment in TNBCs with maintenance treatments. We will further discuss promising results in favor of other new agents including capecitabine, metronomic treatment, and biological drugs.
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http://dx.doi.org/10.1159/000478087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527164PMC
July 2017

CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial.

Lancet Oncol 2017 07 4;18(7):917-928. Epub 2017 Jun 4.

Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA. Electronic address:

Background: CT-P6 is a proposed biosimilar to reference trastuzumab. In this study, we aimed to establish equivalence of CT-P6 to reference trastuzumab in neoadjuvant treatment of HER2-positive early-stage breast cancer.

Methods: In this randomised, double-blind, active-controlled, phase 3 equivalence trial, we recruited women aged 18 years or older with stage I-IIIa operable HER2-positive breast cancer from 112 centres in 23 countries. Inclusion criteria were an Eastern Cooperative Oncology Group performance status score of 0 or 1; a normal left ventricular ejection fraction of at least 55%; adequate bone marrow, hepatic, and renal function; at least one measureable lesion; and known oestrogen and progesterone receptor status. Exclusion criteria included bilateral breast cancer, previous breast cancer treatment, previous anthracycline treatment, and pregnancy or lactation. We randomly allocated patients 1:1 to receive neoadjuvant CT-P6 or reference trastuzumab intravenously (eight cycles, each lasting 3 weeks, for 24 weeks; 8 mg/kg on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2-8) in conjunction with neoadjuvant docetaxel (75 mg/m on day 1 of cycles 1-4) and FEC (fluorouracil [500 mg/m], epirubicin [75 mg/m], and cyclophosphamide [500 mg/m]; day 1 of cycles 5-8) therapy. We stratified randomisation by clinical stage, receptor status, and country and used permuted blocks. We did surgery within 3-6 weeks of the final neoadjuvant study drug dose, followed by an adjuvant treatment period of up to 1 year. We monitored long-term safety and efficacy for 3 years after the last patient was enrolled. Participants and investigators were masked to treatment until study completion. The primary efficacy endpoint, analysed in the per-protocol population, was pathological complete response, assessed via specimens obtained during surgery, analysed by masked central review of local histopathology reports. The equivalence margin was -0·15 to 0·15. This trial is registered with ClinicalTrials.gov, number NCT02162667, and is ongoing, but no longer recruiting.

Findings: Between Aug 7, 2014, and May 6, 2016, we randomly allocated 549 patients (271 [49%] to CT-P6 vs 278 [51%] to reference trastuzumab). A similar proportion of patients achieved pathological complete response with CT-P6 (116 [46·8%; 95% CI 40·4-53·2] of 248 patients) and reference trastuzumab (129 [50·4%; 44·1-56·7] of 256 patients). The 95% CI of the estimated treatment outcome difference (-0·04% [95% CI -0·12 to 0·05]) was within the equivalence margin. 19 (7%) of 271 patients in the CT-P6 group reported serious treatment-emergent adverse events versus 22 (8%) of 278 in the reference trastuzumab group; frequent (occurring in more than one patient) serious adverse events were febrile neutropenia (four [1%] vs one [<1%]) and neutropenia (one [<1%] vs two [1%]). Grade 3 or worse treatment-related adverse events occurred in 17 (6%) of 271 patients in the CT-P6 group versus 23 (8%) of 278 in the reference trastuzumab group; the most frequently reported adverse event was neutropenia in ten (4%) versus 14 (5%).

Interpretation: CT-P6 showed equivalent efficacy to reference trastuzumab and adverse events were similar. Availability of trastuzumab biosimilars could increase access to this targeted therapy for HER2-positive early-stage cancer.

Funding: Celltrion Inc.
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http://dx.doi.org/10.1016/S1470-2045(17)30434-5DOI Listing
July 2017

Cancer Care and Control as a Human Right: Recognizing Global Oncology as an Academic Field.

Am Soc Clin Oncol Educ Book 2017 ;37:409-415

From the Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania; Hematology-Oncology Division, University of Pennsylvania, Philadelphia, PA; National Cancer Institute, Bethesda, MD; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA.

The global burden of cancer incidence and mortality is on the rise. There are major differences in cancer fatality rates due to profound disparities in the burden and resource allocation for cancer care and control in developed compared with developing countries. The right to cancer care and control should be a human right accessible to all patients with cancer, regardless of geographic or economic region, to avoid unnecessary deaths and suffering from cancer. National cancer planning should include an integrated approach that incorporates a continuum of education, prevention, cancer diagnostics, treatment, survivorship, and palliative care. Global oncology as an academic field should offer the knowledge and skills needed to efficiently assess situations and work on solutions, in close partnership. We need medical oncologists, surgical oncologists, pediatric oncologists, gynecologic oncologists, radiologists, and pathologists trained to think about well-tailored resource-stratified solutions to cancer care in the developing world. Moreover, the multidisciplinary fundamental team approach needed to treat most neoplastic diseases requires coordinated investment in several areas. Current innovative approaches have relied on partnerships between academic institutions in developed countries and local governments and ministries of health in developing countries to provide the expertise needed to implement effective cancer control programs. Global oncology is a viable and necessary field that needs to be emphasized because of its critical role in proposing not only solutions in developing countries, but also solutions that can be applied to similar challenges of access to cancer care and control faced by underserved populations in developed countries.
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http://dx.doi.org/10.1200/EDBK_175251DOI Listing
December 2017

Career opportunities and benefits for young oncologists in the European Society for Medical Oncology (ESMO).

ESMO Open 2016 7;1(6):e000107. Epub 2016 Dec 7.

Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.

The European Society for Medical Oncology (ESMO) is one of the leading societies of oncology professionals in the world. Approximately 30% of the 13 000 ESMO members are below the age of 40 and thus meet the society's definition of young oncologists (YOs). ESMO has identified the training and development of YOs as a priority and has therefore established a comprehensive career development programme. This includes a leadership development programme to help identify and develop the future leaders in oncology. Well-trained and highly motivated future generations of multidisciplinary oncologists are essential to ensure the optimal evolution of the field of oncology with the ultimate goal of providing the best possible care to patients with cancer. ESMO's career development portfolio is managed and continuously optimised by several dedicated committees composed of ESMO officers and is directly supervised by the ESMO Executive Board and the ESMO President. It offers unique resources for YOs at all stages of training and includes a broad variety of fellowship opportunities, educational courses, scientific meetings, publications and resources. In this article, we provide an overview of the activities and career development opportunities provided by ESMO to the next generation of oncologists.
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http://dx.doi.org/10.1136/esmoopen-2016-000107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5174792PMC
December 2016

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

ESMO Open 2016 29;1(5):e000097. Epub 2016 Sep 29.

Department of Breast Tumors , Cancer Institute "Ion Chiricuta" , Cluj-Napoca , Romania.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live. Recent progress in the field of cancer research has indeed resulted in diagnostic and therapeutic innovations such as targeted therapies as a standard therapeutic approach or personalised cancer medicine apart from the revival of immunotherapy, requiring specialised training for medical oncology trainees. Thus, several new chapters on technical contents such as molecular pathology, translational research or molecular imaging and on conceptual attitudes towards human principles like genetic counselling or survivorship have been integrated in the GC. The GC edition 2016 consists of 12 sections with 17 subsections, 44 chapters and 35 subchapters, respectively. Besides renewal in its contents, the GC underwent a principal formal change taking into consideration modern didactic principles. It is presented in a template-based format that subcategorises the detailed outcome requirements into learning objectives, awareness, knowledge and skills. Consecutive steps will be those of harmonising and implementing teaching and assessment strategies.
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http://dx.doi.org/10.1136/esmoopen-2016-000097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070299PMC
September 2016

ESMO and WHO: 14 years of working in partnership on cancer control.

ESMO Open 2016 26;1(3):e000012. Epub 2016 May 26.

Department of Breast Tumors , Cancer Institute Ion Chiricuta Cluj-Napoca , Romania.

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http://dx.doi.org/10.1136/esmoopen-2015-000012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5070389PMC
May 2016

The global burden of women's cancers: a grand challenge in global health.

Lancet 2017 02 1;389(10071):847-860. Epub 2016 Nov 1.

Health Economics Group, School of Public Health, Imperial College London, London, UK.

Every year, more than 2 million women worldwide are diagnosed with breast or cervical cancer, yet where a woman lives, her socioeconomic status, and agency largely determines whether she will develop one of these cancers and will ultimately survive. In regions with scarce resources, fragile or fragmented health systems, cancer contributes to the cycle of poverty. Proven and cost-effective interventions are available for both these common cancers, yet for so many women access to these is beyond reach. These inequities highlight the urgent need in low-income and middle-income countries for sustainable investments in the entire continuum of cancer control, from prevention to palliative care, and in the development of high-quality population-based cancer registries. In this first paper of the Series on health, equity, and women's cancers, we describe the burden of breast and cervical cancer, with an emphasis on global and regional trends in incidence, mortality, and survival, and the consequences, especially in socioeconomically disadvantaged women in different settings.
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http://dx.doi.org/10.1016/S0140-6736(16)31392-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191029PMC
February 2017

Changing global policy to deliver safe, equitable, and affordable care for women's cancers.

Lancet 2017 02 1;389(10071):871-880. Epub 2016 Nov 1.

Institute of Cancer Policy, Kings Health Partners Comprehensive Cancer Centre, King's Centre for Global Health, King's Health Partners and King's College London, UK.

Breast and cervical cancer are major threats to the health of women globally, particularly in low-income and middle-income countries. Radical progress to close the global cancer divide for women requires not only evidence-based policy making, but also broad multisectoral collaboration that capitalises on recent progress in the associated domains of women's health and innovative public health approaches to cancer care and control. Such multisectoral collaboration can serve to build health systems for cancer, and more broadly for primary care, surgery, and pathology. This Series paper explores the global health and public policy landscapes that intersect with women's health and global cancer control, with new approaches to bringing policy to action. Cancer is a major global social and political priority, and women's cancers are not only a tractable socioeconomic policy target in themselves, but also an important Trojan horse to drive improved cancer control and care.
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http://dx.doi.org/10.1016/S0140-6736(16)31393-9DOI Listing
February 2017

Bevacizumab plus paclitaxel versus bevacizumab plus capecitabine as first-line treatment for HER2-negative metastatic breast cancer (TURANDOT): primary endpoint results of a randomised, open-label, non-inferiority, phase 3 trial.

Lancet Oncol 2016 Sep 5;17(9):1230-9. Epub 2016 Aug 5.

Department of Medicine I and Comprehensive Cancer Center, Medical University Vienna, Vienna, Austria.

Background: The randomised phase 3 TURANDOT trial compared two approved bevacizumab-containing regimens for HER2-negative metastatic breast cancer in terms of efficacy, safety, and quality of life. The interim analysis did not confirm non-inferior overall survival (stratified hazard ratio [HR] 1·04; 97·5% repeated CI [RCI] -∞ to 1·69). Here we report final results of our study aiming to show non-inferior overall survival with first-line bevacizumab plus capecitabine versus bevacizumab plus paclitaxel for locally recurrent or metastatic breast cancer.

Methods: In this multinational, open-label, randomised phase 3 TURANDOT trial, patients aged 18 years or older who had an Eastern Cooperative Oncology Group performance status 0-2 and measurable or non-measurable HER2-negative locally recurrent or metastatic breast cancer who had received no previous chemotherapy for locally recurrent or metastatic breast cancer were stratified and randomly assigned (1:1) using permuted blocks of size six to either bevacizumab plus paclitaxel (bevacizumab 10 mg/kg on days 1 and 15 plus paclitaxel 90 mg/m(2) on days 1, 8, and 15 every 4 weeks) or bevacizumab plus capecitabine (bevacizumab 15 mg/kg on day 1 plus capecitabine 1000 mg/m(2) twice daily on days 1-14 every 3 weeks) until disease progression, unacceptable toxicity, or withdrawal of consent. Stratification factors were oestrogen or progesterone receptor status, country, and menopausal status. The primary objective was to show non-inferior overall survival with bevacizumab plus capecitabine versus bevacizumab plus paclitaxel in the per-protocol population by rejecting the null hypothesis of inferiority (HR ≥1·33) using a stratified Cox proportional hazard model. This trial is registered with ClinicalTrials.gov, number NCT00600340.

Findings: Between Sept 10, 2008, and Aug 30, 2010, 564 patients were randomised, representing the intent-to-treat population. The per-protocol population comprised 531 patients (266 in the bevacizumab plus paclitaxel group and 265 in the bevacizumab plus capecitabine group). At the final overall survival analysis after 183 deaths (69%) in 266 patients receiving bevacizumab plus paclitaxel and 201 (76%) in 265 receiving bevacizumab plus capecitabine in the per-protocol population, median overall survival was 30·2 months (95% CI 25·6-32·6 months) versus 26·1 months (22·3-29·0), respectively. The stratified HR was 1·02 (97·5% RCI -∞ to 1·26; repeated p=0·0070), indicating non-inferiority. The unstratified Cox model (HR 1·13 [97·5% RCI -∞ to 1·39]; repeated p=0·061) did not support the primary analysis. Intent-to-treat analyses were consistent with the per-protocol results. The most common grade 3 or worse adverse events were neutropenia (54 [19%] of 284 patients in the bevacizumab plus paclitaxel group vs 5 [2%] of 277 patients in the bevacizumab plus capecitabine group), hand-foot syndrome (1 [<1%] vs 43 [16%]), peripheral neuropathy (39 [14%] vs 1 [<1%]), leucopenia (20 [7%] vs 1 [<1%]), and hypertension (12 [4%] vs 16 [6%]). Serious adverse events were reported in 65 (23%) of 284 patients receiving bevacizumab plus paclitaxel and 68 (25%) of 277 receiving bevacizumab plus capecitabine. Deaths in two (1%) of 284 patients in the bevacizumab plus paclitaxel group were deemed by the investigator to be treatment-related. No treatment-related deaths occurred in the bevacizumab plus capecitabine group.

Interpretation: Bevacizumab plus capecitabine represents a valid first-line treatment option for HER2-negative locally recurrent or metastatic breast cancer, offering good tolerability without compromising overall survival compared with bevacizumab plus paclitaxel. Although progression-free survival with the bevacizumab plus capecitabine combination is inferior to that noted with bevacizumab plus paclitaxel, we suggest that physicians should consider possible predictive risk factors for overall survival, individual's treatment priorities, and the differing safety profiles.

Funding: Roche.
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http://dx.doi.org/10.1016/S1470-2045(16)30154-1DOI Listing
September 2016

Cancer Control in Central and Eastern Europe: Current Situation and Recommendations for Improvement.

Oncologist 2016 10 8;21(10):1183-1190. Epub 2016 Jul 8.

Oncology Division, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.

: The incidence of many cancers is higher in Western European (WE) countries, but mortality is frequently higher in Central and Eastern European (CEE) countries. A panel of oncology leaders from CEE countries participating in the South Eastern European Research Oncology Group (SEEROG) was formed in 2015, aiming to analyze the current status and trends of oncology care in CEE and to propose recommendations leading to improved care and outcomes. The SEEROG panel, meeting during the 11th Central European Oncology Congress, proposed the following: (a) national cancer control plans (NCCPs) required in all CEE countries, defining priorities in cancer care, including finance allocation considering limited health care budgets; (b) national cancer registries, describing in detail epidemiological trends; (c) efforts to strengthen comprehensive cancer centers; (d) that multidisciplinary care should be mandated by the NCCPs; (e) that smaller hospitals should be connected to multidisciplinary tumor boards via the Internet, providing access to specialized expertise; (f) nationwide primary prevention programs targeting smoking, obesity, and alcohol consumption and centrally evaluated secondary prevention programs for cervical, colorectal, and breast cancers; (g) prioritize education for all involved in cancer care, including oncology nurses, general practitioners, and palliative care providers; (h) establish outpatient care in day hospitals to reduce costs associated with the current inpatient model of care in CEE countries and to improve patients' quality of life; (i) long-term pharmacoeconomic evaluations of new therapies in CEE countries; (j) increase national oncology budgets in view of the higher mortality rates in CEE compared with WE countries; and (k) CEE countries urgently need help from the European Union to increase and monitor overall investment in cancer care.

Implications For Practice: Significant differences in cancer incidence and mortality have been observed between European countries. While the incidence of many cancer types is higher in Western European (WE) countries, the mortality is generally higher in Central and Eastern Europe (CEE). The primary purpose of this review was to describe the current status and trends of oncology care in the CEE region, to raise awareness among physicians, regulators, and payers, and to propose the most needed changes in order to make the oncology care in CEE closer to the WE standards.
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http://dx.doi.org/10.1634/theoncologist.2016-0137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5061531PMC
October 2016

Low-Dose Oral Cyclophosphamide and Methotrexate Maintenance for Hormone Receptor-Negative Early Breast Cancer: International Breast Cancer Study Group Trial 22-00.

J Clin Oncol 2016 10 20;34(28):3400-8. Epub 2016 Jun 20.

Marco Colleoni, Giuseppe Viale, and Aron Goldhirsch, European Institute of Oncology; Giuseppe Viale, University of Milan, Milan; Lorenzo Gianni, Ospedale degli Infermi, Rimini; Fabio Puglisi, University Hospital of Udine, University of Udine, Udine; Carlo Tondini, Osp. Papa Giovanni XXIII, Bergamo; Katia Cagossi, Ospedale di Carpi, Carpi, Italy; Kathryn P. Gray, Shari Gelber, Richard D. Gelber, Meredith M. Regan, and Karen N. Price, International Breast Cancer Study Group Statistical Center; Kathryn P. Gray, Shari Gelber, Richard D. Gelber, and Meredith M. Regan, Dana-Farber Cancer Institute; Kathryn P. Gray and Richard D. Gelber, Harvard T.H. Chan School of Public Health; Richard D. Gelber and Meredith M. Regan, Harvard Medical School; Richard D. Gelber and Karen N. Price, Frontier Science and Technology Foundation, Boston, MA; István Láng, National Institute of Oncology, Budapest, Hungary; Beat Thürlimann, Kantonsspital, St Gallen; Beat Thürlimann, Elena Kralidis, and Daniel Rauch, Swiss Group for Clinical Cancer Research, Bern; Elena Kralidis, Kantonsspital Aarau, Aarau; Daniel Rauch, Spital Thun, Thun, Switzerland; Ehtesham A. Abdi, The Tweed Head Hospital, Tweed Heads, New South Wales and Griffith University, Southport, Queensland; Ehtesham A. Abdi and Jacquie Chirgwin, Australia and New Zealand Breast Cancer Trials Group; Jacquie Chirgwin, Box Hill and Maroondah Hospitals and Monash University, Melbourne, Victoria; Alan S. Coates, International Breast Cancer Study Group and University of Sydney School of Public Health, Sydney, New South Wales, Australia; Henry L. Gomez, Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru; Barbro K. Linderholm, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, and Sahlgrenska University Hospital, Gothenburg, Sweden; and Alexandru Eniu, Cancer Institute Ion Chiricuta, Cluj, Romania.

Purpose: To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early breast cancer.

Patients And Methods: International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths.

Results: After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio [HR], 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%).

Conclusion: CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5035120PMC
http://dx.doi.org/10.1200/JCO.2015.65.6595DOI Listing
October 2016