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BACKGROUND: Vaccination can have an impact on menstruation, and this impact may be more notable in women with inflammatory gynecological pathologies such as endometriosis. OBJECTIVES: We aimed to investigate the impact of mRNA-based SARS-CoV-2 vaccines on menstrual cycle-related symptoms in women with endometriosis and assess the effect of hormonal therapy on potential SARS-CoV-2 vaccination-induced menstrual changes. DESIGN: A total of 848 women who received at least two doses of mRNA-based COVID-19 vaccines were prospectively recruited: 407 with endometriosis (endometriosis group) and 441 healthy controls (non-endometriosis group). METHODS: Data regarding demographics, clinical characteristics, hormonal treatment, and menstrual-associated symptoms in the first and second cycle after vaccination were collected through an online survey. RESULTS: A similar percentage of patients in both the endometriosis and the non-endometriosis group self-reported menstrual-associated changes the first (52.6% versus 48.8%, respectively) and second cycle after vaccination (29.0% versus 28.1%, respectively). Although the total symptoms recorded were not different between the two groups, several specific symptoms were statistically more frequent in the endometriosis group. These were pain disorders and fatigue in the first cycle after vaccination and pain disorders, menstrual headache and fatigue in the second cycle after vaccination. Bleeding frequency/regularity disorders were found to be more frequent in the non-endometriosis group in the first cycle after vaccination. Patients under hormonal treatment reported fewer changes in menstrual symptoms in the first and second cycle after vaccination compared with those not receiving this treatment. Similarly, patients in the endometriosis group receiving hormonal treatment reported fewer changes in menstrual-associated symptoms compared with those not following any hormonal treatment in the first and second menstrual cycle after the last vaccination. CONCLUSION: Women with endometriosis immunized with mRNA-based SARS-CoV-2 vaccines did not perceive greater worsening or new menstrual-associated symptoms after complete COVID-19 vaccination compared with healthy controls. Hormonal treatment may have a protective effect against worsened or new menstrual symptoms induced by COVID-19 vaccination.
Subject(s)
COVID-19 , Endometriosis , Humans , Female , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , SARS-CoV-2 , Endometriosis/drug therapy , Fatigue , RNA, Messenger , Vaccination/adverse effects , PainABSTRACT
Introduction: Cerebral venous sinus thrombosis (CVST) is a rare but potentially debilitating thrombosis affecting 3-4 cases per million adults in the United States. Risk factors are thought similar to venous thrombosis, but there is little epidemiologic data corroborating this assertion. Concern about a possible association between the Janssen (Johnson and Johnson) and Oxford-AztraZenaca COVID-19 vaccines and cases of CVST resulted in increased global attention to this condition. Thus, large epidemiological assessment of the risk factors, treatment and outcomes of CVST are needed. Objective(s): Estimate the distributions of risk factors antecedent to CVST diagnosis, report CVST treatments in clinical practice, and potential sequelae of CVST in a large retrospective cohort of adults with CVST in the United States. Method(s): MarketScan Commercial and Medicare Supplemental administrative databases were employed to assess CVST diagnosed between 2011 and 2019 in the U.S. Validated International Classification of Disease (ICD) codes and receipt of an outpatient anticoagulant (either oral or subcutaneous anticoagulant) prescription within 30 days of the ICD code identified incident CVST. Antecedent clinical characteristics, treatments, and sequelae of CVST were identified using inpatient, outpatient, and prescription data. For outcomes, proportions and incidence with 95% confidence intervals (CIs) were calculated, stratified by sex. Result(s): We identified 1,869 CVST patients. Of these 1,314 (70%) were female, with 200 (10%) events identified as a pregnancy-related CVST. The average age was 41 years for females and 48 years for men. Among women, 24.7% were on hormonal therapy (oral contraceptive, estrogen, and progestin) prior to diagnosis. Men had a higher prevalence of comorbidities, such as diabetes (15% men vs. 9% women) and cancer (19% men vs. 10% women). Oral anticoagulant (OAC) use was the most common treatment for CVST in both men (88%) and women (85%) and did not vary by sex. Use of procedures to treat CVST, optic nerve fenestration and catheter directed thrombolysis, were 0.5% and 4.1%, respectively. The most common sequela after CVST was incidence of intracranial hypertension (Incidence: 4.2 per 100 person-years;95% CI: 3.3, 5.1) and palliedema was rare. Conclusion(s): Overall, a majority of CVST patients were women of reproductive age. Our findings suggest a potential association with both endogenous (pregnancy) and exogenous (oral contraceptives, HRT) hormones which needs further study. In our sample, CVST was managed with oral anticoagulants, regardless of sex, and intracranial hypertension was elevated following CVST. This large claims-based analysis is a descriptive insight into the risk factors and management of CVST, a rare and debilitating condition.
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Introduction: COVID-19 coagulopathy is associated with poor prognosis and a state of coexisting 'hypercoagulopathy' (HyperC) and hypofibrinolysis, only detected by viscoelastic tests (VET). VET technology has been useful in areas where conventional tests are inadequate, such as screening for HyperC, thrombotic risk assessment and systemic anticoagulants' effect. We aim to characterize the evolution profile of coagulopathy in patients with COVID-19 infection during their intensive care unit (ICU) stay. Method(s): Consecutive recruitment of adult COVID-19 patients admitted to our hospital's ICU, during a 6 months period. Patients with thrombosis in the previous 3 months, pregnancy, under hormone therapy, and congenital coagulopathies were excluded. VET were executed every 5 days, at discharge and in complications and all of them were under low weight molecular heparin (LMWH) therapy. Group 1 (G1), n = 24-less than 10 days in ICU and group 2 (G2), n = 16-more than 10 days in ICU. In G1 there was 1 death (day 3) and in G2 there were 5 deaths (between days 15 and 42). We focused current analysis on VET-Rotem parameters (see Fig. 1). Result(s): Prognostic scores APACHE II, SAPS II and SOFA were higher in G2, but surprisingly G1 patients are more obese. G2 patients had shorter aPTT and lower platelets. The variables CT-HepTem and MCF Extem-MCF-Fib-Tem present a greater difference between groups, but no statistical significance. We observed an initial correlation between basophils number (which is lower) on CT Intem and CT Hep-Tem, lost as progression to cure, probably due to cytoplasm heparin granules. As expected, VET were in accordance with HyperC: short CTs, increased MCFs, and decreased lysis. Conclusion(s): We expected to guide/adjust LMWH dosage, using Rotem profiles, however these were not corrected by LMWH, used transversally, and remained unchanged in all patients during their stay in ICU.
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Background: Transgender women (TGW) are among the population most affected by the HIV epidemic in Argentina, despite a progressive legal framework. TransCITAR is a trans-specific cohort in Argentina that aims to assess physical and mental health among transgender and non-binary people (TGNBP). We present baseline characteristics of TGW. Method(s): TGW attending a trans-friendly clinic to receive HIV/STIs prevention/ treatment, mental health care and/or gender-affirming hormone therapy (GHT) were invited to participate. Semiannual visits including clinical assessments, laboratory tests, and psychosocial interviews were performed. Oral PrEP was offered as part of a combined prevention strategy since September 2021. Result(s): Between September/2019 and August/2022, 500 TGNBP were enrolled, 416 were TGW (median age: 30 years, IQR 25-37). High social vulnerability was observed (Table 1). Regarding trans-specific characteristics, 49.8% reported industrial silicone injections and 36.8% were receiving GHT. 76.9% were sex workers. Baseline STIs prevalence were: HIV 42.3% (10.2% diagnosed at enrolment), syphilis 40% (defined as positive nontreponemal test VDRL with titers of at least 1/8), past HBV 18.5%, chronic HBV 3.8%, HCV antibody positive 2.6%. Only 57% presented HBV protective antibodies titers (HBVsAb>=10UI/ml), 8 TGW were on PreP. For those with HIV, median CD4+ cell count was 602 cells/mm3 (IQR 378-933), 66.5% were on ART at enrolment (53.6% were virally suppressed) and 14.8% initiated at baseline. During 36 months of follow up, 4 TGW died (one AIDS-related and one COVID-19-related). Bivariate analyses showed that a positive HIV diagnosis was independently associated with migration, low level of education, unstable housing, silicone injecion and sex work, while was negatively associated with being on GHT. In multivariable logistic regression, only sociodemographic variables remain associated: migrant (aOR=.487, 95% CI=.304-.768);incomplete high school (aOR=.463, 95% CI=.300=.714);unstable housing (aOR=.614, 95% CI=.401- .940);and sex work (aOR=.324, 95% CI=.177-.593). Conclusion(s): TGW from TransCITAR presented poor health outcomes: high prevalence of HIV/syphilis, high proportion with incomplete/no HBV vaccine and high levels of depression and violence. A comprehensive approach to care and addressing social determinants of health is pivotal to reduce HIV burden in this population.
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Background: The phase III EMERALD trial (NCT03778931) reported significantly prolonged progression-free survival (PFS) and a manageable safety profile with elacestrant vs SoC endocrine therapy (ET) in patients (N=478) with ER+/HER2- advanced or mBC following progression on prior CDK4/6i plus ET. PROs measuring quality of life (QoL) are reported here. Method(s): EMERALD patients (pts) completed 3 PRO tools at prespecified time points: the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and the EuroQoL 5 Dimension 5 Level (EQ-5D-5L). Result(s): The ratio of PROs tools completed vs. PROs tools expected was 80-90% through cycle 4 and approximately 70% at cycle 6;likely due to clinical study period overlapping with COVID-19 period. Overall, the EORTC QLQ-C30 scores were similar for elacestrant and SoC, with no differences across all time points for both functional and symptom scales. However, PRO-CTCAE results showed that fewer pts who received elacestrant reported very severe nausea (4.0% vs 14.3% by cycle 6) or very severe vomiting (9.1% vs 50% by cycle 6) compared with SoC. There were no clinically meaningful differences across all time points in adverse events typically observed with pts with cancer on ET, such as fatigue, nausea, vomiting, joint and muscle pain and hot flashes. EQ-5D-5L scores were generally comparable throughout treatment for both study arms, with elacestrant showing numerically better outcomes vs SoC for mobility, self-care and usual activities. Similar trends were observed for the full intent-to-treat population and in pts with detectable estrogen receptor 1 mutations (ESR1m). Conclusion(s): This analysis confirmed that QoL was maintained between treatment groups in the EMERALD trial. Together with the previously described statistically significant prolonged PFS and manageable safety profile, these PRO results provide additional evidence that oral elacestrant is clinically meaningful in this patient population with limited therapeutic options. Clinical trial identification: NCT03778931. Editorial acknowledgement: Jeffrey Walter, IQVIA. Legal entity responsible for the study: Stemline Therapeutics/Menarini Group. Funding(s): Stemline Therapeutics/Menarini Group. Disclosure: J. Cortes: Financial Interests, Personal, Advisory Board: Roche, Celgene, Cellestia, AstraZeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, MERCK SHARP& DOHME, GSK, LEUKO, Bioasis, Clovis oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks, Reveal Genomics;Financial Interests, Personal, Invited Speaker: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, MERCK SHARP& DOHME, Daiichi Sankyo;Financial Interests, Personal, Other, Consulting/advisor: Expres2ion Biotechnologies;Financial Interests, Personal, Stocks/Shares: MedSIR, Nektar Therapeutics;Financial Interests, Institutional, Research Grant: Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, Guardant Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma B, Queen Mary University of London;Other, Travel cost and expenses: Roche, Novartis, Eisai, Daiichi Sankyo, Pfizer, Gilead, AstraZeneca. F.C. Bidard: Financial Interests, Personal, Advisory Role: Pfizer, AstraZeneca, Lilly, Novartis, Radius Health, Menarini;Financial Interests, Institutional, Advisory Role: Menarini;Financial Interests, Personal, Speaker's Bureau: Pfizer, Novartis, AstraZeneca, Roche, Lilly, Rain Therapeutics;Financial Interests, Institutional, Research Grant: Novartis, Pfizer, Menarini Silicon Biosystems, Prolynx;Financial Interests, Institutional, Other, patents: ESR1 & MSI detection techniques;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche, Pfizer, AstraZeneca, Novartis. A. Bardia: Financial Interests, Personal, Advisory Board: Pfizer, Novartis, Genentech, Merck, Sanofi, Eisa , Lilly, Mersana, AstraZeneca/Daiichi, Menarini, Gilead;Financial Interests, Personal, Royalties: UpToDate;Financial Interests, Institutional, Invited Speaker: Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/AstraZeneca, Eli Lilly.;Non-Financial Interests, Principal Investigator: Gilead, Mersana, AstraZeneca/Daiichi, Novartis, Pfizer, Genentech, Lilly, Merck, Sanofi. V.G. Kaklamani: Financial Interests, Personal, Other, Honoraria: Genentech, Novartis, Pfizer, Genomic Health, Puma Biotechnology, AstraZeneca, Seattle Genetics, Daichi, Gilead Sciences;Financial Interests, Personal, Advisory Role: Amgen, Eisai, Puma Biotechnology, Celldex, AstraZeneca, Athenex, bioTheranostics;Financial Interests, Personal, Speaker's Bureau: Genentech, Novartis, Genomic Health, Puma Biotechnology, Pfizer, AstraZeneca/Daiichi Sankyo;Financial Interests, Personal, Research Grant: Eisai. I. Vlachaki: Financial Interests, Personal, Full or part-time Employment: Menarini Hellas A.E. G. Tonini: Financial Interests, Personal, Full or part-time Employment: Menarini Ricerche S.p.A. N. Habboubi: Financial Interests, Personal, Full or part-time Employment: Stemline Therapeutics;Financial Interests, Personal, Leadership Role: Stemline Therapeutics. P.G. Aftimos: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Macrogenics, Roche, Novartis, Amcure, Servier, G1 Therapeutics, Radius, Deloitte, Menarini, Gilead, Novartis, Eisai, Lilly;Financial Interests, Personal, Invited Speaker: Synthon, Amgen;Financial Interests, Institutional, Research Grant: Roche.Copyright © 2023
ABSTRACT
Background: Mammographic screening programmes reduce breast cancer mortality, but detect many small tumours with favourable biological features which may not progress during a woman's lifetime. Screen-detected cancers are treated with standard surgery and adjuvant therapies, with associated morbidities. There is a need to reduce overtreatment of good prognosis tumours and numerous studies have evaluated the omission of radiotherapy in this context. However, there is little evidence to support surgical de-escalation, although percutaneous minimally invasive treatment approaches have been described. Vacuum-assisted excision (VAE) is in widespread use for management of benign lesions and lesions of uncertain malignant potential. SMALL (ISRCTN 12240119) is designed to determine the feasibility of using this approach for treatment of small invasive tumours detected within the UK NHS Breast Screening Programme (BSP). Method(s): SMALL is a phase III multicentre randomised trial comparing standard surgery with VAE for screendetected good prognosis cancers. The main eligibility criteria are age >=47 years, unifocal grade 1 tumours with maximum diameter 15mm, which are strongly ER/PR+ve and HER2-ve, with negative clinical/radiological axillary staging. Patients are randomised 2:1 in favour of VAE or surgery;with no axillary surgery in the VAE arm. Completeness of excision is assessed radiologically, and if excision is incomplete, patients undergo open surgery. Adjuvant radiotherapy and endocrine therapy are mandated in the VAE arm but may be omitted following surgery. Co-primary end-points are: 1. Noninferiority comparison of the requirement for a second procedure following excision 2. Single arm analysis of local recurrence (LR) at 5 years following VAE Recruitment of 800 patients will permit demonstration of 10% non-inferiority of VAE for requirement of a second procedure. This ensures sufficient patients for single arm analysis of LR rates, where expected LR free survival is 99% at 5 years, with an undesirable survival probability after VAE of 97%. To ensure that the trial as a whole only has 5% alpha, the significance level for each co-primary outcome is set at 2.5% with 90% power. The Data Monitoring Committee will monitor LR events to ensure these do not exceed 3% per year. Secondary outcome measures include time to ipsilateral recurrence, overall survival, complications, quality of life and health economic analysis. A novel feature of SMALL is the integration of a QuinteT Recruitment Intervention (QRI), which aims to optimise recruitment to the study. Recruitment challenges are identified by analysing recruiter/patient interviews and audiorecordings of trial discussions, and by review of trial screening logs, eligibility and recruitment data and study documentation. Solutions to address these are developed collaboratively, including individual/group recruiter feedback and recruitment tips documents. Result(s): SMALL opened in December 2019, but recruitment halted in 2020 for 5 months due to COVID-19. At 7st July 2022, 142 patients had been randomised from 26 centres, with a randomisation rate of approximately 45%, and a per site recruitment rate of 0.4-0.5 patients/month, approaching the feasibility recruitment target of 144 patients. Drawing from preliminary QRI findings and insights from patient representatives, a recruitment tips document has been circulated (on providing balanced information about treatments, encouraging recruiters to engage with patient preferences, and explaining randomisation). Individual recruiter feedback has commenced, with wider feedback delivered across sites via recruitment training workshops. Conclusion(s): Despite pandemic-related challenges, SMALL has an excellent recruitment rate to date and is expected to have a global impact on treatment of breast cancer within mammographic screening programmes.
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Introduction The COVID-19 pandemic and associated social distancing and/or lockdowns have impacted social and personal interactions. Objective To assess COVID's impact on partner relationships, sexual activity, family planning, and menopause management. Methods C Space online communities were surveyed from April 14 to 28, 2021. C Space is an online community platform;each community is unique to the client for which it is designed. For this study, three communities were surveyed: a 100-member community of healthcare professionals (HCPs) who treat women's health issues, a 300-member community of reproductive-age women, and a 300-member community of women in their menopausal years. Of the 100 HCPs, 78 responded (25% OB/GYNs, 49% primary care providers, and 26% nurse practitioners or physician assistants);of the 300 reproductive age women, 184 responded;of the 300 women in their menopausal years, 215 responded. Results Fifty-four percent of reproductive-age women reported that their relationships with their partners have improved during the pandemic, while nearly a third (31%) reported their relationships have suffered. Conversely, just over a third (38%) of menopausal women claim their relationships with their partners improved, while 45% reported that their relationships have suffered. Among women with sexual partners (n=158 reproductive-age women;n=168 menopausal women), 46% of reproductive-age women and 62% of menopausal women reported having sex with the same frequency as before the pandemic. Of the reproductive-age women, 27% reported having sex with more frequency and 22% with less frequency. Among menopausal women, 10% reported having more sex, and 17% reported having less frequent sex than before the pandemic. Nearly half (46%) of those who were considering or actively trying to get pregnant pre-COVID responded they were less likely to try to conceive now, with 36% saying they have not changed, and 18% responded they are more likely to try to conceive.For birth control, the majority (72%) of HCPs reported no change in prescribing, with 14% citing an increase and 14% citing a decline. Of the 75% of reproductive-age women who were taking birth control (n=138), the majority (70%) reported no change in their use of birth control, 22% reported making a change or starting a new treatment, and 11% (n=15) responded that they stopped taking birth control during the pandemic.For menopause management, the majority of HCPs (62%) reported no change in the use of hormone therapy, and nearly a third (31%) reported a decline in use. Of the 20% of menopausal women (n=42) who were on a menopause hormone therapy, over half (52%) responded that they made no change to their treatment, nearly a third (31%) made a change or started a new therapy;17% (n=7) stopped treatment during the pandemic. Conclusions The COVID pandemic has impacted women differently depending on their reproductive or menopause status including their relationships with their partners, sexual activity, family planning and use of birth control or hormone therapy.
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Over the last decade we have witnessed rapid advances in the treatment of patients with metastatic breast cancer (MBC) with seminal discoveries in cancer biology, correlative biomarkers and clinical trials leading to multiple new drug approvals. While these milestones have improved survival, the science of survivorship in this population is just beginning. The diagnosis of MBC is life-changing and requires individualized and multidisciplinary support. The NCI defined the areas of epidemiology and surveillance, symptom management, psychosocial research, health-care delivery, and health behaviors as necessary fields to advance the state of the science in advanced cancer survivors. A multifaceted program addressing these domains is needed to assess MBC patients and their unique and ever-changing needs. With input from patients and providers, program components should include: therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and patient reported outcome (PRO) collection to support patients living with MBC. Input for a program for MBC patients can be guided by a multidisciplinary steering committee in which patient advocates are a major voice. Patients can provide insight into what works for them, and what they are facing may be very different from the experience of an early-stage breast cancer patient. Clinical trials designed to advance the current scientific knowledge of breast cancer treatment are essential to patients living longer, more fulfilled lives with MBC. Clinical trials may include systemic therapy, local therapies such as surgery and radiation for MBC patients, side-effect management and quality of life (may put elsewhere). A comprehensive systemic therapy portfolio should include all biological subtypes as well as recommended treatment options (hormonal therapy, targeted therapy, chemotherapy, and immunotherapy). Multidisciplinary care is necessary to diagnose and treat any condition the MBC patient may encounter and is essential in providing quality care. Comorbidities and debilitating side effects arising from cancer treatment are known to be associated with inferior outcomes. MBC patients may experience lack of familiarity of some providers with novel MBC cancer treatment, side effects, and interactions of their cancer treatment with non-cancer conditions and treatment. With the increasing life expectancy of MBC patients, it is important to manage the medical comorbidities in coordination with the MBC patient's cancer treatment. Integrative Medicine helps support the quality of life of patients through providing clinical modalities such as stress management, yoga, meditation, acupuncture, massage and lifestyle counseling. Supportive care helps support cancer related fatigue and sleep challanges, geriatrics and hospice and palliative care for advanced cancer patients. The role of navigation for MBC patients is unique and should be designed to support the patient's many individual needs. Navigation requires assessment of individual knowledge deficit, coordination of care challenges, internal resource utilization, cultural requests, and emotional health. Navigation should also address the patient's financial and disability questions, medication assistance, symptom management, advanced care planning and goals of care discussions. Additional items to be discussed during navigation visits include primary care provider utilization, COVID-19 vaccination, illness and medication questions, and other patient questions as they arise. A comprehensive registry of MBC patient's medical records and histories will assist researchers in designing future therapeutic and quality of life clinical trials. The categories of patient demographics, clinical variables, pathological variables, treatment variables, outcomes of MBC, and PROs will create a robust registry. A comprehensive patient registry can create a rich database which can guide and inspire future innovative research. Peer support through support groups and peer-to-peer matching s pivotal to MBC patients finding and utilizing their patient voice, emotionally supporting each other and learning from other's similar experiences. Connection between patients and the creation of a community of survivors can empower patients to positively impact their care through self-advocacy and self-efficacy. Continuing patient education is also essential to providing quality cancer care. The format of a weekly virtual education webinars are helpful in creating an engaged patient community and a platform to disseminate educational resources in a reoccurring digestible format. Frequent educational webinars covering a wide variety of topics can positively influence patient interactions with their healthcare providers and influence how patients living with MBC view their own cancer experience. Educational webinars provide opportunities for patients to connect with subject matter experts, other patients like themselves, and share information with their family and friends. Informed patients can discuss and ask questions more confidently with their health care providers about information and services presented during the educational webinars. The symptom profile of patients living with MBC are impacted by numerous variables such as disease burden, treatment plan, comorbidities, supportive regimen etc. The collection of PROs has been shown to improve patient satisfaction with his/her care, improve quality of life, decrease emergency room visits and hospitalizations, and increased overall survival. The routine measurement and management of MBC patients' symptoms has been found to be integral in providing comprehensive cancer treatment. The collection of PROs improves patient and provider communication and elicits the outcome to symptoms that matter most to each patient. Patients diagnosed with MBC are living longer because of the recent advancements in therapeutic treatments. A multifaceted and comprehensive program consisting of therapeutic clinical trials, multidisciplinary specialty care, individualized patient navigation, peer support, continuing education, and PROs collection is integral to fully support patients living with MBC.
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Introduction: More than 2 years after the WHO declaration of a pandemic, SARS-Cov-2 still represents a public health problem The pandemic has increased the complexity of cancer treatments including breast cancer. These difficulties were highlighted in adjuvant treatments but above all in metastatic disease. Vaccination has been one of the most important public health factors that has reduced deaths, hospitalizations and the severity of symptoms related to infection. In metastatic breast cancer hormone receptor positive and HER2/neu negative currently the first line of treatment is given by the association between cyclin 4/6 inhibitors and hormone therapy (aromatase inhibitors or fulvestrant) A well-known and frequent side effect of this therapy is the reduction of white blood cell values and neutrophils. The hypothesis that this study is to evaluate whether treatment with cyclin inhibitors initiated before the period of vaccinations may have influenced, due to the reduction in white blood cell values, an increased risk of infection in these patients. Material(s) and Method(s): In our study, we selected patients who had started treatment with cyclin inhibitors before starting the vaccination cycle (in Italy up to the fourth dose in cancer patients) and continue it without evidence of disease progression. All patients were offered a vaccination cycle with mRNA COVID vaccines and were followed during their cancer treatments. All patients, at least 90 days after the last dose of vaccine, have been tested for antibodies against SARS CoV-2 (trimeric spike protein) with a value expressed in binding antibodies unit (BAU) according to international standard WHO During the observation period (starting from the first dose of vaccine administered) the patients were clinically checked and in case of suspicion of infectious pathology with symptoms suggestive of SARS-COV-19 infection, they were tested with molecular swab Results: We evaluated 52 patients who started cyclin treatment before the vaccination course and who are currently without signs of disease recurrence During the study period we found 14 SARSCOV19 infections (28% of patients) and one patient with two infectious episodes. No patients needed treatment in a hospital or resuscitation setting. All patients have fully recovered from the infection and at most after 21 days have resumed the treatment still in place Statistically, a linear regression calculation was applied to evaluate a functional relationship between variables measured on the basis of sample data. We did not find a relationship between spikes or infections compared to the start date of the vaccination cycle;instead we observed a relationship between the value of the spike and the date of last immunization (considered as an active infection or fourth dose of vaccine) with a reduction in the values the further you go away Conclusion(s): The data of the study show that there is a correlation between the time elapsed between the last vaccination and the risk of getting sick. For this reason, the fourth recall represents a strong help to reduce this risk. We did not find any ranges we could refer to regarding the dosage of trimeric spike protein. Considering the positivity rate of infections that does not exceed the general vaccinated population and the absence of serious infectious symptoms with hospitalization, treatment with cyclin inhibitors appears to be a safe treatment even in a pandemic period. (Table Presented).
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Background: HER2+ mBC remains incurable, with a need for new HER2-directed therapies and regimens, including chemotherapy-free options. Zanidatamab (zani) is a novel HER2-targeted bispecific antibody that binds HER2 in a unique trans configuration, driving multiple mechanisms of antitumor activity, including complement-dependent cytotoxicity. A CDK4/6 inhibitor combined with endocrine therapy is an approved treatment for HER2-negative/HR+ mBC and this combination has also demonstrated encouraging antitumor activity when paired with HER2-targeted therapy(ies) in HER2+/HR+ mBC. Here, we report results from ZWI-ZW25-202 (NCT04224272), an ongoing singlearm phase 2 study of zani combined with palbociclib (palbo) and fulvestrant (fulv) in pts with HER2+/HR+ mBC. Method(s): Eligibility requirements include: HER2+/HR+ unresectable, locally advanced BC or mBC;ECOG PS of 0 or 1;prior treatment with trastuzumab, pertuzumab and T DM1 (additional prior HER2-targeting agents are permitted);and no prior treatment with CDK4/6 inhibitors. Part 1 of the study evaluated the safety and tolerability of the zani/palbo/fulv combination and determined the recommended doses for use in Part 2, where the antitumor activity of the combination is being evaluated. Endpoints include safety outcomes, progression-free survival at 6 months (PFS6), confirmed objective response rate (cORR) per RECIST v1.1;disease control rate (DCR=complete response [CR] plus partial response [PR] plus stable disease [SD]);duration of response (DOR);PFS;and overall survival. Result(s): As of 24 Feb 2022, 34 pts (33 HER2+/HR+ per central analysis) with a median age of 52 (range 36-77) have been treated. In the metastatic setting, pts had received a median (range) of 4 (1-10) prior systemic regimens, including 3 (1-8) different prior HER2 targeted therapies, and 1 (0-4) endocrine therapy. Seven pts (20%) had prior T DXd treatment and 7 pts had prior fulv treatment. All pts received zani (20 mg/kg Q2W) and standard doses of palbo and fulv. Eighteen pts (53%) remained on treatment;median duration of zani treatment was 6.9 mo (range 0.5- 16.3). A dose-limiting toxicity (DLT) of neutropenia occurred in 1 of 7 DLT-evaluable pts in Part 1. Among all pts (n=34), the most common (>20%) treatment (zani, palbo and/or fulv)-related adverse events (TRAEs) were diarrhea (74%), neutrophil count decreased/neutropenia (62%), stomatitis (41%), asthenia (26%), nausea (24%), and anemia (21%). Grade (Gr) >=3 TRAEs in 2 or more pts included neutrophil count decreased/neutropenia (50%), anemia (6%), diarrhea (6%), and thrombocytopenia (6%). AEs of special interest were all Gr <=2 and included 4 pts with cardiac events (LVEF decrease of >=10% from baseline) and 1 pt with infusion-related reaction. There were no treatment-related serious AEs. Palbo was discontinued for 1 pt due to an AE (AST increase);no pt discontinued zani treatment as a result of AEs. Two deaths occurred: 1 due to disease progression and 1 due to an unrelated AE of pneumonia caused by COVID-19. In 29 pts with measurable disease, the cORR was 34.5% (95% CI: 17.9, 54.3), all responses were cPRs, of which 1 is pending CR confirmation. DOR ranged from 2.3 to 14.9+ mo, with 8 confirmed responses ongoing, and the DCR was 93.1% (95% CI: 77.2, 99.2). Interim median PFS was 11.3 mo (range 0.03-16.7;95% CI: 5.6, not estimable). PFS6 analysis is planned following the completion of enrollment. Conclusion(s): Zani in combination with palbo and fulv shows encouraging antitumor activity with durable responses in heavily pretreated pts and a manageable safety profile. This regimen has the potential to be a chemotherapy-free treatment option in pts with HER2+/HR+ mBC. Enrollment in the study is continuing.
ABSTRACT
Background: Multi-parameter tumor gene expression assays (MPAs) are used to estimate individual patient risk and guide chemotherapy use in hormone-sensitive, HER2-negative early breast cancer. The TAILORx trial supports MPA use in a node-negative population. Evidence for MPA use in postmenopausal node-positive breast cancer has been provided by the RxPONDER trial interim analysis but this relies on the absence of superiority in an analysis where >50% of events were unrelated to breast cancer. There is much uncertainty about MPA use for premenopausal patients. OPTIMA (Optimal Personalised Treatment of early breast cancer usIng Multi-parameter Analysis) (ISRCTN42400492) is a prospective international randomized controlled trial designed to validate MPAs as predictors of chemotherapy sensitivity in a largely node-positive breast cancer population. Method(s): OPTIMA is a partially blinded study with an adaptive two-stage design. The trial recruits women and men age 40 or older with resected ER-positive, HER2-negative invasive breast cancer and up to 9 involved axillary lymph nodes. Randomization is to standard management (chemotherapy and endocrine therapy) or to MPA-directed treatment using the Prosigna (PAM50) test. Those with a Prosigna tumor Score (ROR-PT) >60 receive standard management whilst those with a low score (<=60) tumor are treated with endocrine therapy alone. Endocrine therapy for premenopausal women includes ovarian suppression for all participants unless they experience a chemotherapy-induced menopause. Adjuvant abemaciclib is permitted. The trial will be analyzed for (1) non-inferiority of recurrence according to randomization and (2) cost-effectiveness. The key secondary outcome is non-inferiority of recurrence for patients with low ROR-PT score tumors. The efficacy analyses will be performed Per Protocol using Invasive Breast Cancer Free Survival (IBCFS) as the primary outcome measure to limit the risk of a false non-inferiority conclusion. Recruitment of 4500 patients over 8 years will permit demonstration of up to 3% non-inferiority of test-directed treatment with at least 83% power, assuming 5-year IBCFS is 87% with standard management. An integrated qualitative recruitment study addresses challenges to consent and recruitment, building on experience from the feasibility study which found that a multidisciplinary approach is important for recruitment success. OPTIMA is strongly supported by a patient group which has helped design all patient documents and which is represented on the TMG. Result(s): The OPTIMA main trial opened in January 2017 and has continued to recruit throughout the COVID-19 pandemic. Overall recruitment as of 1 July 2022 was 2814 (2593 from UK, 221 from Norway). Patient characteristics are well balanced between the trial arms. Currently 95% of randomized participants are eligible for inclusion in the PP analysis. 66% of the MPA-directed arm participants have been allocated to endocrine therapy only. The test failure rate is < 1%. Conclusion(s): OPTIMA will provide robust unbiased evidence on test-directed chemotherapy safety for both postmenopausal and premenopausal women with 1-3 involved nodes as well as for patients with 4-9 involved nodes and for patients treated with abemaciclib.
ABSTRACT
Objectives: since the beginning of vaccination against SARS-CoV-2 virus one of the most frequent entities of venous thromboembolism (VTE), deep vein thrombosis (DVT), has been scarcely documented. We analyze DVT episodes during vaccination against SARS-CoV-2 period. Material(s) and Method(s): retrospective unicenter analysis including patients diagnosed with DVT (January -September 2021). Patients were divided into two groups, vaccinated and unvaccinated against SARS-CoV-2 28 days prior to DVT symptoms onset. Primary endpoint: DVT severity (pulmonary embolism (PE) and/or hospital admission). Secondary endpoints: DVT risk factors (unprovoked, VTE antecedent, immobilization, trauma, surgery, thrombophilia, hormone therapy and cancer). Result(s): there were 192 DVT diagnoses, 42 (21, 9 %) vaccinated and 150 (78, 1 %) unvaccinated. DVT severity: PE: 52, 4 % vaccinated vs. 62, 7 % controls (p = 0, 228);hospital admission: 52, 4 % vaccinated vs. 62, 4 % unvaccinated (p = 0, 536);unprovoked DVT: 28, 6 % vaccinated vs. 48 % unvaccinated (p = 0, 025);VTE antecedent: 21, 4 % vaccinated vs. 17, 3 % unvaccinated (p = 0, 543): immobilization: 7, 1 % vaccinated vs. 12, 7 % unvaccinated;trauma: 4, 8 % vaccinated vs. 6 % unvaccinated (p = 1);surgery: 4, 8 % vaccinated vs. 1, 3 % unvaccinated (p = 0, 209);thrombophilia: 16, 7 % vaccinated vs. 4 % unvaccinaed (p = 0, 009);hormone theraphy: 9, 5 % vaccinated vs. 3, 3 % unvaccinated (p = 0, 107);cancer: 28, 6 % vaccinated vs. 18, 7 % unvaccinated (p = 0, 162). Multivariate analysis showed a higher risk of DVT in vaccinated patients with thrombophilia, with an OR of 6, 10 (95 % CI, 1, 52-24, 37). Conclusion(s): vaccination against SARS-CoV-2 doesn't seem to increased DVT severity, although a higher incidence of DVT in vaccinated patients with thrombophilia was observed.© Copyright 2023 SEACV.
ABSTRACT
Introduction Due to improvements in breast cancer (BC) diagnostics and treatment, the population of BC survivors is growing. BC treatments may have adverse effects that lead to an increased risk of developing type 2 diabetes mellitus (T2D). It is therefore important to investigate the risk of T2D in patients with BC in general and according to type of adjuvant BC treatment. Objectives To conduct a systematic review and meta-analysis investigating the association between early BC and the risk of subsequent T2D diagnosis. A secondary aim was to examine this association according to type of adjuvant BC treatment-chemotherapy and endocrine therapy (ET). Methods We searched PubMed and Embase using variations of the search terms breast cancer (population), ET, tamoxifen, aromatase inhibitors (AIs) and chemotherapy (exposures), and diabetes mellitus (outcome). Two authors screened papers for eligibility by title and using Covidence and reviewed full texts of eligible papers. Guided by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist, study data were extracted. Using random-effects models, we calculated relative risks (RRs) and associated 95% confidence intervals (CIs) for the association between BC, adjuvant BC treatment (ET overall, tamoxifen, and AIs), and subsequent T2D. We used funnel plots to assess publication bias in the analyses. Results Among 16 eligible studies, 11 reported on T2D risk after BC, chemotherapy, or ET;five studies investigated more than one association. Compared with patients without BC, those with BC had elevated risk of T2D overall (RR=1.27, 95%CI=1.15-1.41), particularly those who received any ET (RR=1.23, 95% CI=1.16 1.32). Among BC patients only, risk of T2D was higher for those who received tamoxifen compared with those who did not receive tamoxifen (RR=1.19, 95% CI=1.13-1.25). Due to few studies, analyses investigating T2D risk after treatment with AIs and chemotherapy were inconclusive. Conclusion Our findings support an association between BC and subsequently elevated risk of T2D, particularly after tamoxifen use. Further research is needed to determine the impact of ET overall, AIs and chemotherapy on the incidence of T2D in patients with early BC.
ABSTRACT
BACKGROUND: In metastatic hormone sensitive prostate cancer (mHSPC), treatment intensification with either docetaxel or an androgen-receptor-axis targeted therapy (ARAT), added to androgen deprivation therapy (ADT) is the new standard of care. To better understand patterns of treatment intensification in Canada and specifically how it has been influenced by the COVID-19 pandemic, we conducted a national survey of genitourinary medical oncologists from across Canada. METHODS: Using SurveyMonkey, we conducted an online survey of 119 medical oncologists in Canada from January 15 to January 27, 2021. The survey consisted of 16 questions, including demographics, and asked specifically about their approach to managing mHSPC before and during the pandemic. RESULTS: Overall there were 50/119 (42%) respondents. Most were male (65%), from Ontario (35%), practicing in academic centers (71%), with 45% reporting their practices focused primarily on genitourinary malignancies and one other tumor site. The majority were in practice 1 to 5 years (34%). Overall 65% indicated their practice patterns had changed since the pandemic, with 51% offering more ARATs and less docetaxel chemotherapy. In low volume mHSPC, the use of ARATs increased from 73% to 79%, while the use of docetaxel remained unaltered at 2%. In high volume disease, the use of ARATs increased from 63% to 84%, while the use of docetaxel decreased from 37% to 14%. Use of granulocyte colony stimulating factor (G-CSF) with docetaxel chemotherapy increased by 35%. Post-pandemic, 45% reported they intend to maintain these changes. Only 18% reported they had prostate cancer patients test positive for COVID-19, and all patients recovered. CONCLUSION: Management of patients with mHSPC in Canada has changed during the pandemic, with increased uptake of ARATs and reduced use of docetaxel, a trend expected to continue beyond the pandemic. How this trend will impact uptake of triplet therapy (ADT + ARAT + Docetaxel), downstream treatment choices and overall outcomes remains to be seen.
Subject(s)
COVID-19 , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Docetaxel/therapeutic use , Pandemics , Androgen Antagonists/therapeutic use , Androgens , COVID-19/epidemiology , Canada/epidemiology , Treatment OutcomeABSTRACT
Excess ovarian activity, chronic anovulation, and androgen excess are the common traits of polycystic ovary syndrome (PCOS). Several advances have been made in understanding the pathophysiology in the process of finding quicker and more effective management measures. Androgen excess in PCOS was found to correlate with markedly elevated luteinizing hormone pulsatility. Impaired insulin response is also attributed to PCOS. Regimen with 3 mg drospirenone + 20 mug ethinyl estradiol combination is beneficial for hormonal imbalance and lipid profile while having a substantial safety profile. Clinical evidence has demonstrated that a 40:1 combination of Myo-inositol and D-chiro-inositol restores ovulation in PCOS women. For women with clomiphene citrate-resistant PCOS, laparoscopic ovarian drilling has proved to be a safe and effective surgical alternative. PCOS is also an indication of bariatric surgery. To conclude, constitutional management by a multidisciplinary team may be helpful for women with PCOS. Lifestyle interventions are best advised and, in so doing, decrease body adiposity and recuperate their metabolic and reproductive health. Copyright © 2022 Current Medical Issues Published by Wolters Kluwer-Medknow.
ABSTRACT
Background: The thrombotic risk associated with SARS-CoV- 2 (COVID-19) is well documented, although there is limited information on how additional prothrombotic risk factors impact persons who contract COVID-19. Certain estrogen containing contraceptives and hormone replacement therapies are also well known to increase the risk of thrombosis. It is unknown if the risks of these agents and concurrent COVID-19 infection are additive. Aim(s): To investigate the relationship between COVID-19 infection and concurrent exogenous estrogen on the rate of thrombotic events. Method(s): A retrospective analysis including all adult female patients diagnosed with COVID-19 between January 2020-2022 at our center also treated with hormone therapy. Female patients on hormone replacement therapy (HRT) for post-menopausal symptoms were included in this analysis. HRT was defined as any treatment consisting of an estrogen analog with or without a progesterone. Thrombotic events were defined as any venous thromboembolism (VTE), cerebrovascular accident (CVA), myocardia infarction (MI), or any arterial clot/embolic event. Events were included if they were recorded as current SNOMED/ICD codes in the same encounter as the diagnosis of COVID-19. Inpatients and outpatients were included in the analysis. Result(s): 92 patients were identified who were diagnosed with COVID-19 while on hormone therapy at the time of diagnosis. 18 of the patients were hospitalized. Mean age was 42 years and 59 years for all patients and hospitalized patients, respectively. The most common estrogen therapies were norethindrone-estradiol (38%) and conjugated estrogen (14.1%). There were 3 (3.2%) total thrombotic events which all occurred in hospitalized patients. 2 patients experienced VTE while 1 patient experienced a cerebrovascular event with arterial clot. Conclusion(s): This retrospective study demonstrates a low rate of thrombosis in patients treated with exogenous estrogen and with COVID-19. The rate of thrombosis in the outpatient setting was low while thrombotic events occurred in hospitalized older patients. Further studies are warranted to explore this association.
ABSTRACT
Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.
ABSTRACT
Background: Little is known about patients’ interactions with Supported Self-Management (SSM) for early breast cancer (EBC), or confidence in managing their care in this pathway. The PRAGMATIC study allowed us to explore these issues. Methods: Three clinical teams in Surrey and Sussex identified EBC patients due to enter SSM. Patients completed standardised questionnaires (separately reported) +/- semi-structured telephone interviews at baseline, 3, 6, 9 and 12 months. The interviews explored how confident patients felt managing their care, accessing services, managing side effects (SEs), and lifestyle changes. Results: 32/110 patients engaged in interviews;data are available for 30/32 at all timepoints. Participants were representative of the whole group in terms of demographics and treatment received. Patients understood the main reasons for SSM were to: a) assume responsibility for their follow up (18/32;56%) and b) save time and money for them and the hospital (16/32;50%). Most maintained (very/somewhat) confidence over time in managing their care and SEs, but were less confident identifying BC related signs/symptoms especially if screen detected. 19 patients contacted the SSM helpline +/- their GP. 15/19 found the helpline easy to use and 6/19 were seen by a healthcare professional. The main triggers for calling were for advice on signs/symptoms and managing SEs. 5/26 (19%) patients on endocrine therapy (ET) had stopped it completely. Most (29/32) were engaged in exercise before diagnosis, and 8/10 who discontinued during treatment resumed afterwards. The COVID-19 pandemic had a negative impact on exercise and socialising. The interviews’ free text provided a plethora of rich data. Qualitative analysis produced four overarching themes: 1) expectations and experiences, 2) emotional wellbeing, 3) clinical concerns, and 4) effect of COVID-19 pandemic. Conclusions: SSM works for most EBC patients. Clinicians could explain that the helpline is available for psychosocial as well as physical concerns. BC teams may want to review how to help screen detected patients recognise BC related signs/symptoms, how to monitor adherence to ET and offer interventions for treatment related SEs. Clinical trial identification: ISRCTN10777283. Legal entity responsible for the study: University of Sussex. Funding: Surrey & Sussex Cancer Alliance. Disclosure: All authors have declared no conflicts of interest.
ABSTRACT
Background: The poly(ADP-ribose) polymerase inhibitor niraparib showed clinical activity in advanced gBRCAm ovarian and breast cancers. LUZERN aims to assess the effectiveness of niraparib plus AI in HR+/HER2–, AI-resistant ABC with a pathogenic variant in homologous recombination-related genes. Here we report findings from the stage 1 interim analysis. Methods: This open-label, single-arm, Simon’s 2-stage, phase II trial is enrolling HR+/HER2– ABC patients (pts) with gBRCAm (cohort A;n=6 in stage 1, n=7 in stage 2) and gBRCA wild-type/HRd (cohort B;n=9 in stage 2). Pts had to have received ≤1 prior line of chemotherapy for ABC, 1–2 prior lines of endocrine therapy for early or ABC with secondary endocrine resistance to the last AI regimen. Pts receive niraparib (200/300mg daily orally) plus AI (same agent given with the prior regimen) on each 28-day cycle. Primary endpoint: clinical benefit rate (CBR) as per RECIST 1.1. Secondary endpoints: overall response rate, progression-free survival (PFS), and safety per CTCAE 5.0. If ≥1/6 pts experienced clinical benefit, the trial should proceed to stage 2. Results: Six pts were enrolled in stage 1. Median age was 46 years (range 32–76), 66.7% of pts had visceral disease, and 83.3% had received prior CDK4/6 inhibitor-containing regimen for ABC. At data cut-off, 50.0% of pts were ongoing and median duration of treatment was 4.6 months (range 2.4–5.7). One patient achieved complete response, meeting the criterion to proceed to stage 2. Median investigator-assessed PFS was 5.3 months (95%CI 3.9–NA). The most frequent adverse events (AEs) of any grade (G) were nausea (3 [50.0%]), neutropenia (2 [33.3%];16.7% G3), constipation (2 [33.3%]), and vomiting (1 [16.7%]). Serious AEs occurred in 3 pts (50.0%;G3 COVID-19 pneumonia;G3 pseudomonal bacteriemia;G2 sacral pain). No treatment-related discontinuations/deaths were reported. Conclusions: Niraparib plus AI showed preliminary activity with a tolerable safety profile in gBRCAm HR+/HER2– AI-resistant ABC pts. Based on the steering committee recommendation, enrolment in cohorts A and B is ongoing. Clinical trial identification: ClinicalTrials.gov identifier: NCT04240106. Legal entity responsible for the study: MEDSIR. Funding: GlaxoSmithKline. Disclosure: J.Á. García Saenz: Financial Interests, Personal, Advisory Board: Seagen, Gilead;Financial Interests, Personal, Invited Speaker: Novartis, Celgene, Eli Lilly, Eisai, AstraZeneca, Daiichi Sankyo, MSD, Exact Sciences;Financial Interests, Institutional, Funding: AstraZeneca. J. De la Haba Rodriguez: Financial Interests, Personal, Other, Consultant and Advisory Role, Research Funding and Speaking: Pfizer, Novartis, Roche, Lilly;Financial Interests, Personal, Other, grant support: Pfizer. J.E. Ales Martínez: Financial Interests, Personal, Other, travel grant: Pfizer;Financial Interests, Personal, Research Grant: MEDSIR. E. Alba Conejo: Financial Interests, Personal, Advisory Role: Roche, Novartis, Pfizer, Lilly, BMS, Astrazeneca, Pierre Fabre, Daiichi, Exact Sciences;Financial Interests, Personal, Research Grant: Pfizer. J. Balmaña: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer;Financial Interests, Institutional, Other, Steering committee member: AstraZeneca;Financial Interests, Institutional, Principal Investigator: Medsir, Pfizer. J.M. Perez Garcia: Financial Interests, Personal, Advisory Role: Lilly,Roche, Eisai, Daichii Sankyo, AstraZeneca, Seattle Genetics, Medsir;Financial Interests, Personal, Other, travel expenses: Roche. M. Sampayo-Cordero: Financial Interests, Personal, Other, honoraria: Medsir, Syntax for Science, Optimapharm, and Ability pharma;Financial Interests, Personal, Research Grant: Medsir;Financial Interests, Personal, Other, travel expenses: Medsir, Syntax for Science, Optimapharm, and Roche;Financial Interests, Personal, Other, consultant: Medsir, Syntax for Science, and Optimapharm;Financial Interests, Personal, Speaker’s Bureau: Medsir;Financial Interests, Personal, Full or part-time Employment: Me sir. A. Malfettone: Non-Financial Interests, Personal, Full or part-time Employment: MEDSIR. J. Cortés: Financial Interests, Personal, Advisory Role: Roche, Celgene, Cellestia, Astrazeneca, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Merck Sharp&Dohme, GSK, Leuko, Bioasis, Clovis Oncology, Boehringer Ingelheim, Ellipses, Hibercell, BioInvent, Gemoab, Gilead, Menarini, Zymeworks;Financial Interests, Personal, Other, honoraria: Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp&Dohme, Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Roche, Ariad pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer healthcare, Eisai, F.Hoffman-La Roche, Guardanth health, Merck Sharp&Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London.;Financial Interests, Personal, Stocks/Shares: MEDSIR, Nektar Pharmaceuticals, Leuko (relative);Financial Interests, Personal, Other, travel, accomodation: Roche, Novartis, Eisai, pfizer, Daiichi Sankyo, Astrazeneca. A. Llombart Cussac: Financial Interests, Personal, Leadership Role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, and MSD;Financial Interests, Personal, Stocks/Shares: MEDSIR and Initia-Research;Financial Interests, Personal, Advisory Role: Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK;Financial Interests, Personal, Speaker’s Bureau: Lilly, AstraZeneca, and MSD;Financial Interests, Personal, Research Grant: Roche, Foundation Medicine, Pierre-Fabre, and Agendia;Financial Interests, Personal, Other, travel compensation: Roche, Lilly, Novartis, Pfizer, and AstraZeneca. All other authors have declared no conflicts of interest.