bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extrapolation of indications and drug interchangeability as barriers to use trastuzumab-dkst biosimilar in Brazil.
Authors: Resende Heloisa Magda , Cardoso Paola , Marassi Pedro , Precivale Maristela Seoanes , Alcantara Alexandre , Cardoso Ana Carolina , Facó Lara Lopes , Alves Leandro Ladislau , Castilho Vivienne Carduz 
Published: May 2020

e13010 Background: Brazil has a complex health-care system which comprises 76% of population in the public unified health system (SUS) and only 24% in private system. Even with most of the population in the public system low resources has been allocated SUS by the government compared with that in private system. Breast cancer (BC) is the more frequent malignant neoplasm in Brazilian women, including HER2 overexpression, and the most are treated in SUS. Although, the HER2 blockage benefits in overall survival have been demonstrated since 2005, the adjuvant and neoadjuvant HER2 blockage was included in SUS protocols only 2013 while the metastatic only 2018. Brazil and development countries have limited accesses to biological drugs and target therapies due to the high cost. The biosimilar technology would improve the patient access to these drugs, health-care savings with efficacy and safety. In 2017, Brazil has approved the first biosimilar in oncology, the anti-HER2 monoclonal antibody trastuzumab-dkst. Our aim is understanding the reasons that hampered the Brazilian oncologists changing practice about biosimilars. Methods: We submitted an on-line survey with 12 questions to 144 Brazilian oncologists which are registered in Brazilian Clinical Oncology Society from North, Northeast, Center east, Center west and Southeast regions in Brazil. The questions were about the anti-HER2 biosimilars knowledge, the manufacturing process, the costs, the biosimilars-based clinical trial, the drug efficacy and safety. Results: We observed that all responders have 9 years experienced oncologist with mean of care 15 patient with HER2 BC per month. In total, 95% of oncologist knows biosimilar definition and 96% assume prescribe biosimilars without doubts. However, 81% oncologists would prescribe biosimilars to all patients, 82% would interchanges and 63% would extrapolate the indication. Conclusions: This survey was conducted to understand the Brazilian oncologist knowledge about biosimilar. We demonstrated a high knowledge of biosimilar definition, however with high percentage indicated adherence barriers. The pharmacovigilance, clinical trials that support biosimilar approval and extrapolation concepts are the main aspects to be addressed. The opportunity of patient access with biosimilars is real and it is the oncologist’s duty to engage in medical education programs. This study could highlight a crucial need for greater strategies to educate physicians, to disseminate biosimilars and provide more informed decision making.
Safety of a trastuzumab biosimilar, used under routine clinical practice conditions in adult HER2+ breast cancer patients in Morocco.
Authors: Errihani Hassan , Berrada Narjiss , Khouchani Mouna , Acharki Abdelkader , Lahbabi Kamal , Jouhadi Hassan , Glaoui Meryem 
Published: May 2020

e13024 Background: Hertraz, the first trastuzumab biosimilar was approved in Morocco in 2017. Real world data on trastuzumab biosimilars are very limited or not available. HERLife is a prospective, non-interventional phase IV study program that investigated the experience of using Hertraz, a biosimilar for trastuzumab (Herceptin), under routine clinical practice conditions in Morocco. The primary aim of this study was to confirm the acceptable safety and tolerability of Hertraz. Methods: Ninety-nine patients with HER2-positive breast cancer treated with Hertraz were enrolled from 8 public and private sector hospitals and followed up for 12 months as part of this non-interventional study. Cardiac events (LVEF) and other unexpected or serious adverse events were monitored. The study arms consisted of patients with early breast cancer (Arm 1, n=70) and metastatic breast cancer (Arm 2, n=29) whose median age was 53 years in both groups. Results: Switching from Herceptin to Hertraz was observed in 45% of 29 MBC patients and 27% of 70 EBC patients. Switching was done at a median of 4th cycle. Pertuzumab was used in combination with Hertraz in 69% and 19% of patients in the metastatic and neoadjuvant settings, respectively. Two patients had a decline in LVEF. One patient treated with Hertraz alone and one patient treated with Hertraz and pertuzumab developed a decrease in LVEF requiring a three-week treatment discontinuation of Hertraz. Treatment of Hertraz was continued after 1 skipped cycle without occurrence of new side effects. No other trastuzumab related adverse events was observed. Four patients in the metastatic group and 2 patients in the early breast cancer arm had a relapse in the 12 months of clinical follow-up. Conclusions: The management of HER2+ breast cancer in Morocco follows the international recommendations. This is the first real world safety data of Hertraz from Morocco. The 12-month follow-up treatment with Hertraz showed an acceptable cardiac safety profile. In cases where there was a switch from Herceptin to Hertraz or Hertraz combined with pertuzumab, the safety profile was similar to that previously reported in other studies.
The effect of everolimus on adipose tissue in patients with metastatic breast cancer.
Authors: Acuna Villaorduna Ana , Ko Heidi , Haken Orli , Deng June , Patel Janki , Podolski Amanda , Munoz-Arcos Laura Sofia , Wang Xiaoyang , Anampa Mesias Jesus Del Santo 
Published: May 2020

e13026 Background: Obesity has been associated with negative outcomes in early breast cancer. Addition of everolimus (Eve) to endocrine therapy improves progression-free survival (PFS) in patients with hormone-receptor (HR) positive, HER2-negative metastatic breast cancer (MBC). Eve targets the mTOR signaling pathway which regulates cell growth/metabolism and has been implicated in obesity and diabetes. Changes in weight and body mass composition and its correlation with PFS have not been described in patients with MBC treated with Eve. We aim to compare total adipose tissue (TAT), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) before and after treatment with Eve in patients with HR+/HER2- MBC. Methods: Patients with metastatic HR+/HER2- MBC treated with Eve and endocrine therapy (Eve/ET) between 2012 and 2018 were identified. Each Eve/ET case was matched to a patient who received endocrine therapy alone (ET) by age at diagnosis (+/- 5 yrs), body mass index [BMI] (+/-5 kg/m2) and visceral metastatic disease. VAT, SAT, TAT, and skeletal muscle index (SMI) were measured by computerized tomography at L3 level using TOMOVISION software prior to treatment initiation (T0) and after 3-6 months of treatment (T3). TAT was defined as SAT + VAT and sarcopenia as SMI < 40. Paired t-test and Wilcoxon paired-test were used to compare body composition parameters at T3 vs T0 in Eve/ET and ET groups. Results: 78 patients (Eve/ET: 41 and ET: 37) with a median age of 65.5 yrs were included. Of these, 16 (21.3%) were Non-Hispanic White, 31 (41.3%) were Non-Hispanic Black and 27 (36%) were Hispanics. Visceral metastases were seen in 57 (73.1%) cases. Mean weight, BMI, VAT and SAT at T0 were 70.8 kg, 27.4 kg/m2, 170.1 cm2 and 196.1 cm2, respectively and did not differ between Eve/ET and ET groups at baseline. At T3, there was a reduction in TAT (348.4 to 289.2 cm2, p < 0.01) and SAT (181.7 to 142.7 cm2, p < 0.01) in the Eve/HT group; while there were no significant changes in TAT (373.1 to 363.9 cm2, p = 0.39) or SAT (212 to 221.8 cm2, p = 0.33) in the ET group. No changes in visceral fat %, VAT/SAT ratio and sarcopenia between T0 and T3 in either treatment group were seen. In patients treated with Eve/ET, there were no differences in PFS between low TAT-loss (TAT loss < 40 cm2) and high TAT-loss (TAT loss > 40 cm2) (3.6 vs 4.8 months, p = 0.97). Conclusions: Eve induces TAT loss in patients with HR+/HER2- MBC, specifically driven by decrease in SAT. The pathophysiology of this association is still to be discerned. Further studies are required to evaluate TAT or SAT as a predictive/prognostic biomarker in patients receiving Eve.
Efficacy of palbociclib after everolimus in hormone receptor-positive, HER2-negative advanced breast cancer.
Authors: Kovac Anja , Grasic Kuhar Cvetka , Ovcaricek Tanja , Matos Erika , Mencinger Marina , Borstnar Simona 
Published: May 2020

e13030 Background: Palbociclib and other selective cyclin-dependent kinases 4 and 6 inhibitors in combination with endocrine therapy (ET) have become the standard of care in the treatment of patients with hormone receptor-positive (HR+), HER2-negative advanced breast cancer (ABC). Their role in the first and second line of therapy is well established, whereas their use in subsequent lines and after treatment with everolimus remains unclear. Methods: We performed retrospective observational study of all patients who initiated treatment with palbociclib at the Institute of Oncology Ljubljana between March 8, 2018 and March 8, 2019 and received at least two prior lines of treatment for ABC. We collected individual patient data from electronic medical records. Patients were divided in two groups – everolimus-pretreated (group A) and everolimus-naïve (group B). The primary study outcomes were clinical benefit rate (CBR), time to treatment failure (TTF) and overall survival (OS). Results: Overall, 65 patients´ data was evaluated. The majority of patients (n = 50, 76.9%) received palbociclib in combination with fulvestrant, others (n = 15, 23.1%) with aromatase inhibitors. There were 25 (38.5%) patients in group A and 40 (61.5%) in group B. Patients´ and previous treatment characteristics are shown in table. CBR was the same, 40%, in both groups. The median follow-up time was 14.9 months. The median TTF was 5.28 months for the whole group, 5.0 months for everolimus-pretreated and 5.5 months for everolimus-naïve group (p = 0.7). The median OS was 18.1 months for the whole group, 14 months for everolimus-pretreated and 18.1 months for everolimus- naïve group (p = 0.7). Conclusions: Patients with HR+, HER-2-negative ABC benefit from addition of palbociclib to ET after two lines of prior systemic therapy. The benefit remained unchanged if the patients were previously treated with everolimus. [Table: see text]
CDK4/6 inhibitors beyond second line, is it worthy? A real-world data experience.
Authors: Falcón Alejandro , Salvador Bofill Javier , Montaño Alvaro , Benavent Marta , Gonzalez Rosario , Ruiz Borrego Manuel 
Published: May 2020

e13033 Background: CDK4/6 inhibitors as Palbociclib, Ribociclib and Abemaciclib has become the first or second line in advanced or metastatic luminal breast cancer HER2 negative. We only have data about the use of Abemaciclib in monotherapy beyond second line. Methods: We have analyzed 200 patients treated in our center with CDK4/6 inhibitors since 2017. All of them belong to clinical practice, out of clinical trial context. The effect of CDK4/6 inhibitors was analyzed using logistic regression analyses. Results: 34 patients were treated beyond second line of treatment with a medium follow-up of 18 months. CDK4/6 inhibitors were used as fourth line as medium (range 3-9), median age of 45 years, 1 male. 52% patients had visceral disease and 8.8% were primary hormone resistance. 64.6% were treated with palbociclib, 26.5% with ribociclib and 8.8% with abemaciclib. 52.9% were asociated with Fulvestrant, 44.1% with Letrozol and 2.9% with tamoxifen. Clinical benefit of 67.6% and response rate of 32.3%. Similar toxicities to previosly published trials were observed. Median progression-free survival was 14.2 months and median overal survival was 26.6 months. Non statistical difference were observed by luminal subtype, number of prior lines, type of hormonal therapy or CDK4/6 inhibitor used. Conclusions: Despite of the small population, we can summarized that CDK4/6 inhibitors associated to hormonal therapy is a good option for patients previosly treated in the metastatic setting. We need further investigation to understand which patient will benefit from treatment with this drugs in advanced lines.
Real-world hematologic toxicities in patients > 70 versus < 69 with ER positive metastatic breast cancer on CDK 4/6 inhibitors: Single-institution retrospective study.
Authors: Olazagasti Coral , Liu Wingsze , Lee Chung-Shien , Decina Taylor , Pappas Karalyn , Cheng Kit 
Published: May 2020

e13039 Background: Since 2015, CDK4/6 inhibitors (CDKi) have become part of standard of care in the treatment ER-positive, Her2Neu negative of metastatic breast cancer (MBC). Hematologic toxicity from CDKi are common. Pooled analysis of prior randomized trials did not show hematologic toxicity between younger and older adult age groups. We sought to review generalizability of these findings to our community population. Methods: We conducted a retrospective single institution retrospective study on patients who were treated with CDKi from 2015 to 2019. Patients were stratified according to age > 70 years and < 69 years. Data from absolute neutrophil count, hemoglobin and platelet count on Days 1 and 15 of the first 2 cycles were graded for hematologic toxicity according to CTCAE v 5.0. Our primary objective was to assess any difference in grade of hematologic toxicities in the different age groups. Our secondary objective was to analyze the association between hematologic toxicities with the presence or absence of bone metastasis and/or prior chemotherapy exposure. Results: A total of 220 patients were reviewed, 140 were < 69 years and 80 > 70 years. There was no significant effect of time (p = 0.91) with respect to the outcome of hematologic toxicity adjusting for age (p = 0.16). Seventy-seven percent (171/220) of patients had evidence of bone marrow (BM) involvement. There was no significant difference in the grade of any hematologic toxicities over time (p = 0.97) and underlying BM disease (p = 0.20). On the other hand, 50% (111/220) patients had previously received an average of one line of chemotherapy. There was significant positive correlation between lines of therapy and grade of neutropenia (rS= 0.25, p = 0.0028). Overall, the estimated median progression free survival (PFS) was 19.1 months. The median overall survival could not be estimated. Conclusions: Our single institution experience does not show significant hematologic toxicity between patient age groups nor evidence of bone metastasis. However, prior exposure to chemotherapy can have a significant effect in the grade of neutropenia. Our study revealed that there is no difference in PFS according to dosing or age which correlates with current literature.
Palbociclib in hormone positive metastatic breast cancer: A real world multicenter Indian experience.
Authors: Rauthan Amit , Patil Poonam , Somashekhar S.P. , Jacob Linu Abraham , D Lokanatha , Kumar Kishore , Keechilat Pavithran , Vijayakumar DK , Patil Shekar , P Shashidhara H , Zaveri Shabber , Yashas Nitin 
Published: May 2020

e13057 Background: Palbociclib, a selective CDK4/6 inhibitor, in combination with hormonal therapy has become the standard of care in the treatment of hormonal positive (HR+) metastatic breast cancer (MBC). There is limited efficacy and safety data in Indian patients. Methods: This is a multicenter retrospective study of real world experience of patients with HR+, Her 2 neu negative MBC who received Palbociclib in 5 centers of south India between Oct 2016 and Aug 2019. Endpoints were overall response rate (ORR), progression free survival (PFS) and toxicity. Results: 133 patients received Palbociclib; 83 (62.4%) in the first line setting (hormone naïve MBC) and 50 (37.6%) in the second line (MBC progressed on at least one line of hormonal therapy). Median age was 56 years (range 48-76). All patients started with 125mg/day. In the 83 first line patients, 46 (55.4%) had denovo MBC, 37 (44.6%) had post-adjuvant relapse. 38 (45.8%) had bone only and 45 (54.2%) had visceral metastases. Letrozole was the companion drug in 76%, Fulvestrant in 18%, Exemestane in 6%. 5 (6%) patients achieved complete response (CR), 54 (65%) partial response (PR), 12 (14.5%) stable disease (SD) and 12 (14.5%) had progressive disease (PD). ORR was 71%. At a median followup of 18 months, the median PFS was not reached (maximum ongoing followup 38 months). The median PFS in the denovo metastatic disease versus relapsed disease was not reached versus 18 months (p = 0.021). The median PFS was significantly better in bone only versus visceral metastases (not reached versus 28 months, p = 0.007). In the 50 second line patients, 15 (30%) had bone only and 35 (70%) had visceral metastases. Companion drug was Fulvestrant in 64%, Letrozole in 20%, Exemestane in 16%. 60% received prior chemotherapy. Best response was CR 3 (6%), PR 23 (46%), SD 4 (8%), PD 17 (34%), not assessed 3 (6%). ORR was 52%. The median PFS was 14 months. PFS in bone only versus visceral disease was 14 months versus 13 months (p = 0.382). Neutropenia was present in 75.2%, thrombocytopenia in 19.5%, anaemia in 18%. Neutropenia was grade 1 in 26%, grade 2 in 51%, grade 3 in 23%; with no febrile neutropenia. 30% had dose delays and 8.2% had dose reduction. Conclusions: Palbociclib has resulted in similar efficacy and safety in Indian patients as the PALOMA trials. Neutropenia was the commonest side effect, which was uncomplicated and easily managed with dose delays. Using CDK4/6 inhibitors with hormonal therapy has become the standard of care in HR+ MBC Indian patients.
Metaplastic breast cancer: A retrospective analysis over 14 years.
Authors: Bhasin Pooja Gogia , Desai Gopal R 
Published: May 2020

e13066 Background: Metaplastic breast carcinoma (MBC), a rare entity, is known to be an aggressive form of breast cancer. With few published reports and scant literature, there are no current guidelines for this type of cancer. The aim of the study is to describe the patient characteristics, pathologic features, treatment and clinical outcomes of the patients with MBC at our institution. Methods: A retrospective analysis of patient charts with histologically confirmed MBC from 2001 to 2014 was done. Clinical information was abstracted from the medical records. Medical records were reviewed for patient age, tumor size, nodal status, tumor grade, hormone receptor status, treatment, recurrence rates and survival characteristics. Results: Twenty-three patients were identified with a median age at diagnosis of 59 years (range 42-91 years). The median tumor size was 2.1 cm (range 0.4-4.5 cm). Most tumors were grade 3 (73.9 %). None of the patients had metastatic disease at presentation. 17 patients were node negative (74%). 13 patients (56.5 %) were triple negative. 6 patients (26 %) underwent mastectomy and 17 underwent lumpectomy. 16 out of 23 patients underwent post-operative radiation therapy. The 5-year disease free survival was 73.9 % and 5-year overall survival was 82.6%. The tumor size was more than or equal to 2.4 cm in all the patients with recurrence. 60 % of the patients with recurrence were triple negative and 20% were Her2 neu positive. 33.33 % patients were poorly differentiated on histology. Conclusions: Based on our analysis and review of literature, MBC has higher tumor grade, hormone receptor negativity and lesser nodal involvement on presentation. Various studies have shown that tumor size is often large on presentation. In our study, tumor size was modest on presentation. Hence, our survival rates are better than seen with other studies. As per our analysis and as demonstrated by other studies, tumor size is an independent risk factor for recurrence. Other ominous factors for recurrence are triple negative hormone status and poorly differentiated tumor as seen in our case. Further studies and clinical trials comparing with infiltrating ductal carcinoma are needed to understand this rare breast cancer.
Asymptomatic versus symptomatic metastatic breast cancer: Potential effects on prognosis and quality adjusted life years (QALYs).
Authors: Yamanouchi Kosho , Maeda Shigeto , Kuroki Tamotsu 
Published: May 2020

e13073 Background: After radical surgery for breast cancer, routine laboratory or imaging studies for metastases screening are not indicated in the absence of clinical signs and symptoms suggestive of recurrence. While the goal of therapy is the extension of survival and maintenance of quality of life (QOL), therapies themselves could induce adverse events, resulting in deterioration of QOL. We evaluated quality adjusted life years (QALYs), which is survival adjusted by QOL, of the patients with recurrent breast cancer retrospectively and adequate follow-up measures. Methods: Fifty seven patients with recurrent breast cancer who died already were included. Survival curves were partitioned into two health states: time with ≥ grade 2 chemotherapy-related toxicity (TOX) and time without toxicity (TWiST). QALYs were acquired as follows: QALYs = TWiST + 0.7 * TOX. We compared clinical factors in the patients between with (symptomatic group, n = 32) and without symptoms (asymptomatic group, n = 25). Results: The median age of the patient at diagnosis of recurrence was 57 years. Luminal (hormone receptors (HR) - and human epidermal growth factor receptor-2 (HER2) -), HER2 (HER2 +), triple negative (TN) (HR - and HER2 -), and unknown were 29, 7, 15, and 6 cases, respectively. The proportion of HER2 and TN was significantly higher in the symptomatic group than that in the asymptomatic group (58.6, 21.7 %, p < 0.05). 44.6 % of the patients had visceral metastases at diagnosis of recurrence and the proportions were not different between the groups. Although post recurrent survival (PRS) was shorter significantly in the symptomatic group (22.5, 42,0 months, p < 0.01), overall survival from diagnosis of primary breast cancer (OS) was identical (60.5, 91.0 months). Additionally, QALYs after recurrence was shorter in the symptomatic group (23.0, 41.1 months, p < 0.01) and QALYs from diagnosis of primary breast cancer was identical (58.7, 91.0 months). Conclusions: Although there was no significant difference in OS between the both groups, the duration of therapy received was longer in the symptomatic group. In the present study, we acquired limited information due to retrospective manner. Prospective evaluation of QALYs, including patient reported outcome and symptoms derived from cancer itself, would turn out adequate measures of follow-up after radical surgery for primary breast cancer.