First-line Treatment For Women Research Articles

Cost-effectiveness of the addition of CDK4/6 inhibitors to standard endocrine therapy in first-line treatment of women with advanced HR+/HER2- breast cancer in Mexico.

To estimate the cost-effectiveness of adding a CDK4/6 inhibitor to standard endocrine therapy in the first-line setting for advanced HR+/HER2- breast cancer in postmenopausal and premenopausal women, from the perspective of the Mexican public healthcare system. We used a partitioned survival model to simulate relevant health outcomes in a synthetic cohort of patients with breast cancer derived from the PALOMA-2, MONALEESA-2, MONARCH-3 trials for postmenopausal patients, and from the MONALEESA-7 study for premenopausal patients. Effectiveness was measured in life years gained. Cost-effectiveness is reported through incremental cost-effectiveness ratios (ICER). In postmenopausal patients, palbociclib led to an increase of 1.51 life years, ribociclib of 1.58years, and abemaciclib of 1.75years, compared to letrozole alone. The ICER was 36,648 USD, 32,422 USD, and 26,888 USD, respectively. In premenopausal patients, ribociclib led to an increase of 1.82 life years when added to goserelin and endocrine therapy, with an ICER of 44,579 USD. In the cost minimization analysis, for postmenopausal patients, ribociclib was the treatment with the highest costs due to follow-up requirements. Palbociclib, ribociclib, and abemaciclib demonstrated a significant increase in effectiveness in postmenopausal patients, and ribociclib in premenopausal patients, when added to standard endocrine therapy for patients with advanced HR+/HER2- breast cancer. At the national stablished willingness to pay, only the addition of abemaciclib to standard endocrine therapy in postmenopausal women would be considered cost-effective. However, differences on results between therapies for postmenopausal patients were not statistically significant.

(054) Improvement of Lower Urinary Tract Symptoms by Treating Pelvic Floor Muscle Increased Tone

Abstract Introduction Physical therapy is first line treatment for women diagnosed with urinary incontinence (UI). However, while pelvic floor muscle (PMF) strengthening for decreased PFM tone is well published, there is minimal data evaluating appropriate treatment strategies for PFMs increased tone on the improving of UI. Objective To retrospectively analyze the effectiveness of normalization of PFM tone on lower urinary tract symptoms (LUTS) of women with either stress urinary incontinence (SUI), overactive bladder (OAB), or urgency urinary incontinence (UUI). Methods Medical records of women who received physical therapy care from January 2017 till July 2021 for LUTS and who had increased PFM tone were included in this retrospective, cohort study. Exclusion criteria: previous pelvic surgeries or physiotherapy treatment for PFM dysfunction, neuromuscular diseases, lichen sclerosus et atrophicus, and missing data. Baseline and post-treatment assessments were carried out for: (i) LUTS trough voiding diaries (data on urinary frequency, episodes of SUI, urinary urgency and UUI, nocturia and enuresis) and Questionnaire for Urinary Incontinence Diagnosis (QUID), assessing LUTS with scores from 0-15 (no symptoms to maximum symptomatology); (ii.) PFM tone, via digital palpation using a 7-level grading score (Reissing Scale) from -3 (most decreased) to +3 (most increased PFM tone); (iii.) pain intensity - PFMs active trigger points (TP) were each rated from 0 (no pain) to 10 (worst possible pain) according to the Numerical Rate Scale (NRS); and (iv.) PFM power of contraction (PERFECT scheme). Treatment consisted of in-office physical therapy (including myofascial release, manual stretching of the vaginal walls and perineal massage) twice weekly during six weeks. Self-vaginal stretching and perineal massage was to be done daily by the women over the duration of care. Results Women (n=127) presenting LUTS and increased PFM tone were diagnosed with SUI (35%), OAB (21%), or mixed UI (44%). Mean age was 52 (±13.4). Women presenting normal PFM tone (0) after treatment showed a greater power of PFM contraction when compared to those who maintained tone (≥1) after treatment (2.7±0.9 vs. 2.2±0.6; p=.01; d=0.6) as well as a reduction in SUI episodes (0.1±0.31 vs. 1±1.5; p=.01; d=0.8). Women with improved SUI symptoms at the post-treatment assessment (QUID-SUI score ≤1) compared to those who maintained them (QUID-SUI score >1), had decreased mean of pain intensity (0.88±1.77 vs. 2.59±2.78; p=.002; d=.73) as well as at any given PFM TP according to NRS (0.97±1.92 vs. 2.90± 3.26; p=.002; d=.72). With regard to symptoms of OAB, women who scored ≤1 on the QUID-OAB post-treatment compared to those who scored >1 also showed significant decrease in pain intensity at all trigger points (0.85±1.76 vs. 2.16±2.52; p=.009; d=.60), with maximum pain intensity (0.94±2 .00 vs. 2.42±2.92; p=.010; d=.59), and experienced decreased tone in the right vaginal wall (0.05±0.22 vs. 0.41±0.73; p=.019; d=.67). A mild correlation between increased tone and SUI (p=0.04; r=0.32), episodes of urinary urgency (p=0.02; r=0.37), and nocturia (p=0.007; r=0.43) were shown. Conclusions These study findings points toward to the importance of focusing physiotherapeutic techniques to normalize PFM tone in women with LUTS and increased PFM tone. Disclosure No

Efficacy of supervised pelvic floor muscle training with a home-based biofeedback device for urinary incontinence in postpartum women: protocol for a multicentre randomised controlled trial

IntroductionSupervised pelvic floor muscle training (PFMT) of at least 3 months duration has been strongly recommended as a first-line treatment for women with stress urinary incontinence (SUI) or SUI-predominant mixed...

Efficacy and Safety of Trastuzumab as a Single Agent in First-Line Treatment of HER2-Overexpressing Metastatic Breast Cancer.

To evaluate the efficacy and safety of first-line, single-agent trastuzumab in women with HER2-overexpressing metastatic breast cancer. One hundred fourteen women with HER2-overexpressing metastatic breast cancer were randomized to receive first-line treatment with trastuzumab 4 mg/kg loading dose, followed by 2 mg/kg weekly, or a higher 8 mg/kg loading dose, followed by 4 mg/kg weekly. The objective response rate was 26% (95% confidence interval [CI], 18.2% to 34.4%), with seven complete and 23 partial responses. Response rates in 111 assessable patients with 3+ and 2+ HER2 overexpression by immunohistochemistry (IHC) were 35% (95% CI, 24.4% to 44.7%) and none (95% CI, 0% to 15.5%), respectively. The clinical benefit rates in assessable patients with 3+ and 2+ HER2 overexpression were 48% and 7%, respectively. The response rates in 108 assessable patients with and without HER2 gene amplification by fluorescence in situ hybridization (FISH) analysis were 34% (95% CI, 23.9% to 45.7%) and 7% (95% CI, 0.8% to 22.8%), respectively. Seventeen (57%) of 30 patients with an objective response and 22 (51%) of 43 patients with clinical benefit had not experienced disease progression at follow-up at 12 months or later. The most common treatment-related adverse events were chills (25% of patients), asthenia (23%), fever (22%), pain (18%), and nausea (14%). Cardiac dysfunction occurred in two patients (2%); both had histories of cardiac disease and did not require additional intervention after discontinuation of trastuzumab. There was no clear evidence of a dose-response relationship for response, survival, or adverse events. Single-agent trastuzumab is active and well tolerated as first-line treatment of women with metastatic breast cancer with HER2 3+ overexpression by IHC or gene amplification by FISH.

Inclusion Complex of Clomiphene Citrate with Hydroxypropyl-β-Cyclodextrin for Intravenous Injection: Formulation and Stability Studies.

Clomiphene citrate is the first-line treatment for women with abnormal or failed ovulation. Currently, it is available as oral tablets, and the parenteral formulation does not exist. In this study, we prepared clomiphene citrate-hydroxypropyl-β-cyclodextrin inclusion complex for its use in intravenous injection. The inclusion complex was characterized in the liquid state (phase solubility) and solid state by differential scanning calorimetry, Fourier transform infrared spectroscopy, and nuclear magnetic resonance spectroscopy analyses. The sterile intravenous injection containing 0.5% clomiphene citrate was prepared and characterized for its physical properties, assay, pH, and osmolality. A stability-indicating high-performance liquid chromatography (HPLC) method for the injection was developed. The HPLC method was validated for the assay, linearity, precision and repeatability, benchtop stability, and forced degradation to elute clomiphene isomers from the degradation products. The injection was packed in sterile 10-ml glass vials with butyl rubber stoppers and stored at 40°C, room temperature, and 4°C. The samples at 0, 0.5, 1, 2, 3, and 6months were analyzed for clarity, pH, osmolality, and drug assay. The HPLC method was linear (R2 = 0.9999), precise (0.86% relative standard deviation), and stability indicating. The stability data at the accelerated (40°C) storage condition for 6months showed satisfactory results: the drug assay in the injection was between 90 and 105%, the injection remained clear, pH was between 4.0 and 4.4, and osmolality was between 270 and 350mOsm. The stability data suggests that the product is stable and meets the given analytical specifications.

Spontaneous pregnancy rate after fallopian tube recanalization for unilateral obstruction with a patent contralateral tube

BackgroundInfertility is a common sociomedical problem worldwide, affecting up to 15% of couples. Tubal obstruction is currently one of the most important causes of female infertility. This study was designed to determine the spontaneous pregnancy rate in patients undergoing unilateral transcervical fallopian tube recanalization, performed by an interventional radiologist, for proximal fallopian tube obstruction with a patent contralateral tube. The secondary objective was to analyze pregnancy rates in relation to the type and duration of infertility, patient age, and body mass index.ResultsThirty-eight patients with unilateral tube obstruction were included in this study. Transcervical fallopian tube recanalization was successfully performed in all cohorts. At the one-year follow-up; 13 women (34.2%) had become pregnant, nine (23.7%) delivered healthy babies, and four (10.5%) had miscarriages. The time interval between the application of the technique and spontaneous pregnancy was 1–12 months, with a mean of approximately 4 months. Multivariate analysis showed a significantly higher pregnancy rate in young (< 35 years), nonobese (BMI < 30 kg/m2) females with a history of primary infertility for < 5 years. Minor complications were noted in 27 patients (71%). No major complications were noted.ConclusionsOur study showed that transcervical fallopian tube recanalization of proximal fallopian tube obstruction with a patent contralateral tube increased the spontaneous pregnancy rate in cases of tubal factor infertility. Moreover, transcervical fallopian tube recanalization is recommended as a first-line treatment for women with unilateral proximal fallopian tube obstruction and a patent contralateral tube owing to the low risks associated.

P-627 Pregnancy Rate and Outcomes Following a Randomized Controlled Three-component Lifestyle Intervention in Women with PCOS

Abstract Study question What is the impact of a three-component lifestyle intervention on the pregnancy rate, time to pregnancy and pregnancy complications in women with polycystic ovary syndrome? Summary answer A non-significant positive trend in pregnancy outcomes was demonstrated in favor of the lifestyle intervention groups, in line with the weight loss achieved per group. What is known already PCOS (polycystic ovary syndrome) is associated with overweight and obesity. Women with PCOS and overweight or obesity present with more pronounced reproductive derangements. Moreover, when pregnant, pregnancy complications such as gestational diabetes, hypertensive disorders and preterm birth seem to be more prevalent in this population. The first line treatment for women with PCOS and overweight or obesity is a multi-component lifestyle intervention. Data on pregnancy outcomes after multi-component lifestyle interventions in women with PCOS are scarce. Study design, size, duration The present study is a one-year randomized controlled trial to investigate the effect of a three-component (cognitive behavioral therapy, healthy diet and physical therapy) lifestyle intervention (LSI) with or without Short Message Service (SMS) on pregnancy leading to live birth, pregnancy complications and outcomes within 24 months after the start of the lifestyle intervention compared to care as usual (CAU). Participants/materials, setting, methods Women diagnosed with PCOS according to the Rotterdam 2003 criteria and a BMI above 25 kg/m² were included. A total of 183 participants were randomly assigned to three groups: 1) three-component lifestyle intervention with SMS (SMS+); 2) three-component lifestyle intervention without SMS (SMS-); 3) care as usual (CAU): encourage to lose weight autonomously (control group). Pregnancy and neonatal outcomes were collected from the Dutch Bureau of Statistics (CBS) combined with the Dutch Perinatal registry (Perined). Main results and the role of chance Within 24 months after the start of the intervention the pregnancy rate leading to live birth was 41.7% (25/60) within SMS+, 38.1% (24/63) within SMS- and 38.3% (23/60) within CAU. This was non-significant between the groups. Mean time to pregnancy for SMS+ was 18.3 months, 19.1 months for SMS- and 19.4 months for CAU (p = 0.775). Gestational diabetes (LSI: 8.2% vs CAU: 21.7%, p = 0.133), hypertensive disorders (LSI: 8.2% vs CAU: 13.0%, p = 0.673) and preterm birth (LSI: 12.2% vs CAU: 17.4%, p = 0.716) rates were all lower in the LSI groups (SMS+ and SMS- combined) compared to CAU. Limitations, reasons for caution Although significantly less than the LSI groups, even the CAU group achieved weight loss, which may give an underestimation of the effect of the lifestyle intervention with regard to pregnancy outcomes. Wider implications of the findings Weight loss overall seems to have a positive effect on pregnancy outcomes, and multi-component lifestyle interventions are needed to achieve weight loss. Trial registration number NTR2450

P-580 Cumulative live birth rate of oocyte in-vitro maturation with a pre-maturation step in women with polycystic ovary syndrome or high antral follicle count

Abstract Study question What is the cumulative live birth rate (CLBR) at 24 months of women undergoing oocyte in vitro maturation (IVM) a with pre-maturation step (CAPA-IVM)? Summary answer The CLBR at 24 months with CAPA-IVM was 38.2%. What is known already IVM with a pre-maturation step, known as capacitation IVM (CAPA-IVM) improves the competence of oocytes matured in-vitro by sustaining meiotic arrest to allow the synchronization of cytoplasmic and genetic maturation of the oocytes. Results from a randomized controlled trial showed that CAPA-IVM resulted in a live birth rate after the first transfer of 35.2% which was non-inferior to IVF. There is a lack of data on cumulative live birth following CAPA-IVM. Study design, size, duration A multi-center, retrospective study, performed at IVFMD, My Duc Hospital and IVFMD Phu Nhuan, My Duc Phu Nhuan Hospital from 1 January 2017 to 31 December 2019. Participants/materials, setting, methods All women with polycystic ovary syndrome (PCOS) or high antral follicle count (AFC) treated with a CAPA-IVM cycle were recruited to the study. All embryos were frozen at day 3. Cumulative live birth was difined as at least one live birth resulting from initiated CAPA-IVM cycle. If the women did not return for embryo transfer, outcomes were followed up until 24 months from aspiration day. Logistic regression was performed to assess which factors predicted CLBR. Main results and the role of chance Between 1 January 2019 and 31 December 2019, there were 374 eligible women included in the study, among them, 368 patients had embryos for transfer (98.4%) and six patients had no embryo for transfer (1.6%). A total of 496 frozen embryo transfer (FET) cycles from 368 patients were performed. Mean age and body max index (BMI) were 29.5±3.21 years and 22.3±3.09, respectively. The maturation rate was 63.2%. The median number of embryos was 4.0 [2.00; 6.00]. The cumulative clinical pregnancy rate was 60.4%, cumulative ongoing pregnancy rate was 51.6%. At 24 months after starting the treatment, the CLBR of CAPA-IVM was 38.2%. Multivariate analysis showed that patient age and number of metaphase II oocytes were the predictive factors for cumulative live birth after CAPA-IVM. Limitations, reasons for caution The study limitation derives from its retrospective nature. The generalizability of the study may be limited due to the single ethnicity group. Wider implications of the findings In patients with PCOS or high AFC, CAPA-IVM was viable and resulted in acceptable CLBR. CAPA-IVM may be the first-line treatment for women with PCOS or high AFC requiring assisted reproduction. Trial registration number not applicable

Nicardipine for treating severe antepartum hypertension during pregnancy: Nine years of experience in more than 800 women.

Women with severe hypertension during pregnancy require prompt stabilization with a combination of magnesium sulfate and rapidly acting intravenously administered antihypertensives. It remains unknown which antihypertensive is best suited for pregnancy. The present study evaluated the intravenous use of the calcium antagonist, nicardipine. This multicenter, retrospective case series included all pregnant women beyond 20 weeks of gestation with severe antepartum hypertension that were treated with intravenous nicardipine. successful treatment, time to successful treatment, and maternal safety. Severe hypertension was defined as systolic blood pressure (SBP) of 160 mm Hg or more and/or diastolic blood pressure (DBP) of 110 mm Hg or more. This study included 830 women. After 1 h of treatment, two-thirds of the women had SBP below 160 mm Hg and DBP below 100 mm Hg. In three out of four women, the mean arterial pressure was below 120 mm Hg. Within 2 h of treatment, 77.4% of women achieved successful treatment. In all cases, nicardipine was eventually effective. Within the first 2 h, 42.7% of women experienced temporary low DBP (ie below 70 mm Hg) without clinical consequences for the mother or fetus. In all cases, the low DBP resolved after discontinuing or reducing the dosage of nicardipine. One case of fetal distress was attributable to maternal hypotension, and a cesarean section was performed at more than 2 h after initiating therapy. During treatment, headache, nausea, and vomiting decreased significantly. To date, this was the largest case-series study on the use of nicardipine for treating severe antepartum hypertension in pregnancy. We found that nicardipine could effectively and safely treat this condition. Based on its high success rate and acceptable safety profile, nicardipine should be considered a first-line treatment in women with severe hypertension in pregnancy.

How does weekly compare with tri-weekly paclitaxel with carboplatin for first-line treatment of women with epithelial ovarian cancer?

How does weekly compare with tri-weekly paclitaxel with carboplatin for first-line treatment of women with epithelial ovarian cancer?

Weekly versus tri-weekly paclitaxel with carboplatin for first-line treatment in women with epithelial ovarian cancer.

Epithelial ovarian cancer is the sixth most common cancer worldwide: 295,414 new cases were diagnosed in 2018, with 184,799 deaths. The lack of an effective screening strategy has led to the majority of women being diagnosed at an advanced stage. For these women, intravenous carboplatin combined with paclitaxel for six cycles is widely accepted as the standard first-line treatment for epithelial ovarian cancer, in combination with debulking surgery. However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting. To compare the efficacy and tolerability of intravenous weekly paclitaxel with that of tri-weekly paclitaxel, in combination with intravenous carboplatin, as first-line treatment for epithelial ovarian cancer (defined as epithelial ovarian, primary peritoneal and fallopian tube cancer). We searched CENTRAL, MEDLINE, and Embase databases for relevant studies up to 15 November 2021, using keywords and MeSH terms. We additionally handsearched conference libraries, online clinical trial databases and screened through lists of retrieved references. We Included randomised controlled trials (RCTs) comparing weekly paclitaxel in combination with carboplatin versus tri-weekly paclitaxel in combination with carboplatin, for treatment of newly-diagnosed epithelial ovarian cancer. We used the hazard ratio (HR) to estimate the primary efficacy outcomes progression-free (PFS) and overall survival (OS). We used the risk ratio (RR) to estimate the primary toxicity outcome of severe neutropenia and secondary outcomes of quality of life (QoL) and treatment-related adverse events. Two review authors independently selected studies, extracted data, and assessed risk of bias, using standard Cochrane methodological procedures. We included individual participant data (IPD) from one of the included studies, ICON-8, provided by the study team. We analysed data using a random-effects model in Review Manager 5.4 software. Additionally, we reconstructed IPD for PFS and OS data from published Kaplan-Meier curves from all studies and subsequently pooled these to analyse the two primary efficacy outcomes. From 2469 records, we identified four eligible RCTs with data for 3699 participants. All eligible studies were included in the main meta-analysis and reported on PFS and OS. There was likely a slight improvement in PFS when paclitaxel was dosed weekly compared to tri-weekly (HR 0.89, 95% confidence interval (CI) 0.81 to 0.98; 4 studies, 3699 participants; moderate-certainty evidence). We found little to no improvement in OS when paclitaxel was dosed weekly compared to tri-weekly (HR 0.92, 95% CI 0.79 to 1.06; 4 studies, 3699 participants; high-certainty evidence). There was likely little to no difference in high-grade (grade 3 or 4) neutropenia when paclitaxel was dosed weekly compared to tri-weekly (RR 1.11, 95% CI 0.86 to 1.43; 4 studies, 3639 participants; moderate-certainty evidence). However, weekly paclitaxel increased high-grade (grade 3 or 4) anaemia when compared to tri-weekly dosing (RR 1.57, 95% CI 1.12 to 2.20; 4 studies, 3639 participants; high-certainty evidence). There may be little to no difference in high-grade neuropathy when paclitaxel was dosed weekly compared to tri-weekly (RR 1.12, 95% CI 0.64 to 1.94; 4 studies, 3639 participants; low-certainty evidence). The overall risk of detection bias and performance bias was low for OS, but was unclear for other outcomes, as treatments were not blinded. The risk of bias in other domains was low or unclear. We note that OS data were immature for three of the included studies (GOG-0262, ICON-8 and MITO-7). Weekly paclitaxel combined with carboplatin for first-line treatment of epithelial ovarian cancer likely improves PFS slightly (moderate-certainty evidence) but not OS (high-certainty evidence), compared to tri-weekly paclitaxel combined with carboplatin. However, this was associated with increased risk for high-grade anaemia, treatment discontinuation, dose delays and dose omissions (high- to low-certainty evidence). Our findings may not apply to women receiving bevacizumab in first-line therapy, those receiving treatment in the neo-adjuvant setting, or those with rare subtypes of clear cell or mucinous ovarian cancer.

Abstract P1-18-15: Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) locally advanced or metastatic breast cancer: Fourth interim analysis from the RIBANNA study

Abstract Background: Ribociclib (RIB; a selective CDK4/6 inhibitor) + endocrine therapy (ET; aromatase inhibitor or fulvestrant along with ovarian suppression in pre- and perimenopausal patients [pts]) received USFDA and EMA approval for pre-, peri- and postmenopausal pts with HR+, HER2- advanced breast cancer (ABC) based on results from phase 3 MONALEESA (ML) trials. In ML-2 trial, first-line treatment (tx) with RIB + letrozole (LET) vs placebo (PBO) + LET significantly improved median progression-free survival (mPFS) in postmenopausal pts with HR+, HER2- ABC. In ML-3 and ML-7 trials, RIB + ET vs PBO + ET showed a significant improvement in mPFS and overall survival among pts with HR+, HER2- ABC, irrespective of menopausal status, line of tx and combination partner. Real-world evidence on the effectiveness, safety, and tolerability of RIB + ET in pts with HR+, HER2- ABC would help to gain insight into routine clinical practice. Methods: RIBANNA is a prospective, noninterventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal pts who received first-line tx with RIB + ET, or ET alone or chemotherapy (CT) for HR+, HER2- ABC in accordance with German tx guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. The third interim analysis data from RIBANNA study was presented in SABCS 2020. Fourth interim analysis data will be presented during SABCS 2021. Results: Till February 11, 2021, 2594 pts were included in the study (RIB + ET, n = 2183; ET, n = 229; CT, n = 182) and the enrollment was stopped; however, pt follow-up will be continued for an additional 4 years. For the fourth interim analysis, full analysis set (comprising all pts, except screening failures and locked pts, who received at least one dose of study medication [safety analysis set] and for whom ≥ 1 post-baseline evaluation was recorded) included 2131 pts (RIB + ET, n = 1814 [81.2%]; ET, n = 175 [73.8%]; CT, n = 142 [72.1%]), while the safety analysis set comprised 2452 pts (RIB + ET, n = 2062 [92.3%]; ET, n = 216 [91.1%]; CT, n = 174 [88.3%]). Until last patient first visit, among 2594 treated pts (including screening failures), data from first-line (1L) tx are available for 2452 pts (94.5%), from second-line (2L) tx for 343 pts (13.2%), and from third-line (3L) tx for 74 pts (2.9%, Table 1). Overall, 23.9%, 27.9%, and 43.4% of pts discontinued the study in RIB + ET, ET, and CT cohorts, respectively. The fourth interim analysis is planned in October 2021, and the final baseline demographic data as well as updated information on safety will be presented during SABCS 2021. Conclusion: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. The data from fourth interim analysis, which is planned in October 2021, including final baseline demographic data and updated safety data will be presented. Table 1. Patient disposition following last patient first visit on February 11, 2021PatientsTotal. (N = 2594). n (%)RIB + AI/FUL (n = 2183). n (%)ET (n = 229). n (%)CT. (n = 182). n (%)Includeda2594 (100.0)2183 (100.0)229 (100.0)182 (100.0)Treated (including screening failures)2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)1L therapyb2452 (94.5)2062 (94.5)216 (94.3)174 (95.6)2L therapyb343 (13.2)264 (12.1)36 (15.7)43 (23.6)3L therapyb74 (2.9)53 (2.4)10 (4.4)11 (6.0)4L therapyb7 (0.3)7 (0.3)0 (0.0)0 (0.0)Discontinued studyc664 (25.6)521 (23.9)64 (27.9)79 (43.4)aAll pts signing informed consent form, bNumber of data set available till February11, 2021, cEnd of documentation with reason other than ‘end of study. Citation Format: Diana Lüftner, Cosima Brucker, Thomas Decker, Peter Fasching, Thomas Göhler, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Marion van Mackelenbergh, Frederik Marmé, Arnd Nusch, Beate Rautenberg, Toralf Reimer, Marcus Schmidt, Rudolf Weide, Pauline Wimberger, Naiba Nabieva, Christian Roos, Achim Wöckel. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) locally advanced or metastatic breast cancer: Fourth interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-15.

Contraception in the context of PCOS

Polycystic ovary syndrome is a frequent endocrinopathy, affecting between 8% and 13% of women of childbearing age and characterized by hyperandrogenism, chronic anovulation and polycystic ovary morphology. Women with PCOS also have a higher prevalence of obesity, metabolic disorders and an increased risk of diabetes, systemic hypertension and dyslipidemia. The first-line treatment for women with PCOS who do not plan to conceive in the short term includes lifestyle changes and combined oral contraceptives, offering, in addition to contraception, endometrial protection and reduction of hyperandrogenism. Progestin-only contraceptives are recommended for women with contraindications to estrogen contained in combined oral contraceptives. Cosmetic procedures can be added to pharmacological treatment for hirsutism. Severe cases may require anti-androgen drugs which will be combined with contraception. For overweight patients with cardiometabolic risk factors, including insulin resistance or dysglycemia, metformin may also be combined with contraception. In conclusion, the choice of contraception in women with PCOS includes an approach tailored to the individual needs of each patient.

The effects of insulin therapy on maternal blood pressure and weight in women with gestational diabetes mellitus

BackgroundAlthough insulin therapy achieves effective glycemic control, it may aggravate hyperinsulinemia. Nonetheless the benefits of insulin as first-line treatment for women with GDM are controversial. This work aimed to investigate the effect of insulin on maternal GDM.MethodsThis retrospective cohort study recruited 708 women with GDM of whom 616 underwent lifestyle intervention and 92 were prescribed insulin therapy. Differences in variables between the two groups were analyzed by univariate analysis and multivariate analysis. Propensity score matching was used to control for age, pre-pregnancy BMI, time and BP at GDM diagnosis, and family history of diabetes and hypertension. Paired sample test was applied to evaluate the changes in BP after intervention in the two groups of women.ResultsThere was no significant difference in mode of delivery, newborn weight or incidence of macrosomia between women prescribed insulin and those who adopted lifestyle modifications. Insulin therapy was associated with a slight increase in maternal weight compared with the lifestyle intervention group and was attributed to short-term treatment (about 12 weeks). In addition, insulin therapy remarkably increased maternal blood pressure, an effect that persisted after matching age, pre-pregnancy BMI, time and BP at GDM diagnosis, and family history of diabetes and hypertension. Between commencing insulin therapy and delivery, systolic blood pressure significantly increased by 6mmHg (P = 0.015) and diastolic blood pressure by 9 mmHg (P < 0.001). Increase in BP was significantly higher in the insulin group compared with the lifestyle intervention group (P < 0.001). Logistic regression analysis with enter selection confirmed that insulin therapy was closely correlated with development of gestational hypertension (GH).ConclusionsThis work suggested that short-term insulin therapy for GDM was associated with a slight increase in maternal weight but a significant risk of increasing maternal blood pressure.

O-105 High prevalence of obesity and polycystic ovary syndrome in an online community seeking assistance with fertility

Abstract Study question What are the characteristics of a large online community of women trying to conceive and what are the factors that predict infertility in this group? Summary answer The cohort was not characterized by increased age, though age, obesity and PCOS strongly correlated with fertility. PCOS may be under-recognized within some ethnic groups. What is known already Obesity, polycystic ovary syndrome (PCOS), and age are among the primary predictors of infertility in women. However, most studies assessing reproductive health employ populations who have sought medical assistance for infertility or associated disorders, potentially leading to populations more likely to exhibit disorders such as PCOS or to be of increased age. Characterization of factors affecting fertility in a general population may highlight epidemiological influences that should be better addressed to aid women trying to conceive. Study design, size, duration This study employed users of the mobile application, FertilityAnswers, for people searching for answers to fertility problems. Users answered a short survey describing themselves, their fertility history and goals. Recruitment for this study began in March 2017 and ended in January 2021. 61814 participants downloaded the application during this period, and 56878 at least provided their age. The primary inclusion criteria were that study participants be US females over eighteen years of age. Participants/materials, setting, methods Regression models estimated beta coefficients and corresponding confidence intervals. Multivariable models determined independence of variables. To model PCOS, the available data in January 2020 was split randomly into discovery and validation subsets. Missing value imputation using random forests was performed in the discovery dataset. Minimal feature selection used a linear regression model penalized with a lasso and elastic net. The model was then validated on samples collected after the model was trained and tested. Main results and the role of chance Age was a significant predictor of fertility in this study (p &amp;lt; 1x10-10). However, the distribution of age in the cohort was very similar to that of women at first birth in the United States, therefore we did not observe the majority of study participants to be of an age where in a typical clinical setting age-related concerns would be addressed (i.e., approaching 35 years). Using National Center for Health Statistics data, the mean age of 1,433,604 women at first birth in 2018 in the US was younger than the study population (restricted to those without children) by only one month. Obesity was of increased prevalence in this cohort, with 55% being obese, compared to 37% in an age-matched US population. Participants reported a variety of fertility-related disorders, with polycystic ovary syndrome (PCOS) being most prevalent (19.0%), followed by endometriosis (6.0%). Prediction of PCOS, performed by modeling on training and test sets (10476 and 5312 participants) and then validating with an additional 21097 participants collected after the model creation, found that African-Americans and Latino members of this cohort had a lower self-reported rate of the disorder than was anticipated by the model, in contrast to those of Asian or European descent. Limitations, reasons for caution All health data was self-reported. Additionally, as this is the initial survey of this population, no a priori hypotheses were made as to the expected relationships to be observed. Instead, all associations were examined, and measurements of false discovery rate were estimated. Wider implications of the findings We found that women were seeking answers about infertility at ages coincident with that of their peers achieving first pregnancies. ART is often not a first-line treatment for women of this age, but there may be a disconnect between traditional clinical response to this group and their desire for assistance. Trial registration number not applicable

Cost-Effectiveness Analysis of an Interdisciplinary Lifestyle Intervention Targeting Women With Obesity and Infertility in Comparison to Usual Care

Although lifestyle modification is considered as the first-line treatment for women with obesity and infertility, these women generally do not have access to a program supporting them in adopting healthy habits that is integrated to fertility care. Implementing such a program requires to demonstrate its efficiency. The purpose of this study was to conduct a cost-effectiveness analysis (CEA) of an interdisciplinary lifestyle intervention (Fit-for-Fertility (FFF) program) for women with obesity and infertility, in comparison with the usual care protocol, i.e. fertility treatments. Methods: A CEA was conducted alongside a randomized controlled trial, recruiting women at the fertility clinic of the Centre hospitalier universitaire de Sherbrooke. Women were randomized to: i) the intervention group (IG): FFF program alone for 6 months (individual follow-ups every 6 weeks and 12 group sessions), and in combination with usual care for infertility after 6 months if not pregnant; or ii) control group (CG): usual care from the outset. Data were collected in both groups, during 18 months or until the end of the pregnancy for those who became pregnant. Costs related to the management of infertility, obesity, pregnancy and childbirth, and the FFF program were considered and collected by self-reported questionnaires, review of medical records and administrative databases. Live birth (LB) rate was used to assess effectiveness. The CEA’s parameter of interest was the incremental cost-effectiveness ratio (ICER), calculated by non-parametric bootstrap with 5,000 iterations. All costs are in Canadian dollars, 2019. Results: A total of 130 women were randomized (65 CG, 65 IG). We present results for the 108 women (57 CG, 51 IG) who completed at least 6 months in the study. We observed an absolute difference of 14.2% (p=0.328) in LB rate between groups (IG: 51.0%; CG: 36.8%). Total mean costs per patient were significantly higher in the IG vs the CG for healthcare system’s ($5,660 ± $3,200 vs $3,631 ± $3,389; p=0.002) and society’s ($9,745 ± $5,899 vs $6,898 ± 7,021; p=0.026) perspectives. We observed an ICER of $12,633 per additional LB [$5,319-$19,947] from the healthcare system’s perspective, and $5,980 [$3,086-$8 874] from the patients’ perspective. Overall, the ICER for the society’s perspective, which includes both previous perspectives, was estimated at $24,393 per additional LB [$15,509-$33,276]. Conclusion: According to our results, a lifestyle intervention may be clinically more effective than the usual protocol of care for women with obesity and infertility, but generates higher costs as well, resulting in a positive ICER (of $12,600 per additional life birth for the healthcare system). Such an intervention could be considered efficient compared to the usual standard of care, but studies are needed to assess the willingness to pay of stakeholders for this type of intervention.

Abstract PS10-16: Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study

Abstract Background: In MONALEESA-3 and MONALEESA-7 trials, ribociclib (RIB, a selective CDK4/6 inhibitor) in combination with endocrine therapy (aromatase inhibitor [AI] or fulvestrant [FUL]) demonstrated a significant prolongation of overall survival among patients with breast cancer (BC), regardless of menopausal status and treatment-line. In the premenopausal or perimenopausal women, RIB + AI/FUL should be combined with a luteinizing hormone-releasing hormone agonist. The real-world evidence for the effectiveness, safety, and tolerability of RIB + AI/FUL in the routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a prospective, non-interventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal women (planned, n = 3020) treated with RIB + AI/FUL, or endocrine monotherapy (ET), or chemotherapy (CT) as the first-line treatment for HR+/HER2- aBC in accordance with German guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. Updated data on baseline demographics and safety analysis will be presented. Additionally, first experience with CANKADO, an innovative digital and patient-friendly application for electrocardiogram (ECG) measurement, are described. By combining this app to Kardia mobile (AliveCor’s single lead device), single-lead ECG can be recorded and sent via the CANKADO app for a cardiologist to read over. The cardiologist reviews the measurements, and reports the corrected QT interval by Fredericia (QTcF) results towards the trial site. Impact of the use of CANKADO onto the clinical routine will be analyzed. Results: For the second interim analysis, 1141 patients were enrolled until July 12th, 2019, while the full analysis set comprised 813 patients (Table 1). Median duration of RIB exposure in patients on RIB + AI/FUL vs total population was 151 vs 150 days respectively. At cut-off date, patients received first-line (89%, n = 1016), second-line (7%, n = 82), and third-line treatments (1%, n = 11). A starting dose of 600 mg per day for RIB in the first-line setting was seen in most of the patients (85%); data of second-line patients will be reported later. The first-line mean daily dose of RIB was 451.6 mg/day RIB was prescribed mainly in combination with letrozole (75%), fulvestrant (12%), anastrozole (7%), and exemestane (6%). A total of 62% of patients in the study were documented as therapy-naïve for ET. Of 424 patients with early breast cancer, 129 (30%) had documented prior CT without ET. The most common all-grade adverse events frequently noted in RIB + AI/FUL cohort in comparison with other cohorts were nausea (RIB [19%] vs ET [9%] vs CT [11%]), neutropenia (19% vs 1% vs 10%), fatigue (17% vs 9% vs 14%), and leukopenia (14% vs 4% vs 12%). The usage of CANKADO application to assess QTcF was initiated in the year 2019 and first data will be presented. Conclusion: RIBANNA study showed diverse population characteristics among the patients who received RIB treatment in a real-world setting. The third interim analysis is planned in October 2020, and the updated baseline data, information on safety, digital ECG measurement using CANKADO application will be presented. Baseline Demographic Characteristics as of Second Interim AnalysisDemographic VariableRIB + AI/FUL (n = 658)Endocrine Therapy (n = 78)Chemotherapy (n = 77)Mean age, years (SD)67 (11)72 (12)62 (10)Mean time since initial diagnosis, years6.17.23.6T stage at baseline*, n (%)TX204 (31)28 (36)18 (23)T0+T1132 (20)12 (15)11 (14)T2-T4302 (46)35 (45)42 (54)N stage at baseline*, n (%)NX212 (32)29 (37)28 (36)N0+N1317 (48)36 (46)35 (46)N2+N3108 (16)10 (13)8 (10)M stage at baseline*, n (%)MX6 (1)0 (0)0 (0)M018 (3)1 (1)1 (1)M1616 (94)75 (96)71 (92)Metastatic location at baseline*, n (%)CNS, liver, lungs258 (39)14 (18)42 (54)Bone only181 (28)42 (54)11 (14)Skin, lymph nodes, other149 (23)16 (20)14 (18)*Remaining cases are missing.CNS, central nervous system. Citation Format: Achim Wöckel, Cosima Brucker, Thomas Decker, Jörg Falbrede, Helmut Forstbauer, Thomas Göhler, Oliver Hoffmann, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Diana Lüftner, Frederik Marmé, Arnd Nusch, Toralf Reimer, Christian Roos, Marcus Schmidt, Rudolf Weide, Peter Fasching. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS10-16.

RANDOMIZED PHASE III TRIAL COMPARING EPIRUBICIN/ DOXORUBICIN PLUS DOCETAXEL AND EPIRUBICIN/ DOXORUBICIN PLUS PACLITAXEL AS FIRST LINE TREATMENT IN WOMEN WITH ADVANCED BREAST CANCER

Background: The purpose of this study was to compare Epirubicin/ doxorubicin plus docetaxel and Epirubicin/ doxorubicin plus paclitaxel as first line treatment in women with advanced breast cancer.&#x0D; Patients and methods: previously untreated patients with advanced breast cancer randomly assigned to recieve Epirubicin 75mg/m2 and docetaxel 75 mg/m2 (ED) 1-hour intravenous (IV) infusion every 21 days, Epirubicin 75 mg/m2 and paclitaxel 175 mg/m2 (EP) 3-hour IV infusion every 21 days, Intravenous bolus injections of doxorubicin 50 mg/m2 and docetaxel 75 mg/m2 (DD) administered as a 1-hour intravenous infusion every 21 days and doxorubicin 50 mg/m2 and paclitaxel 175 mg/m2 (DP) administered as a 1-hour intravenous infusion every 21 days. Previous anthracycline-based neo-adjuvant chemotherapy was allowed if completed ? 1 year before entering the study.&#x0D; Results: Ten women patients were treated on arm ED &amp;EP and median TTP was 10 versus 11 months, 50 women patients were trated on DD &amp; DP cand median TTP was 8.5 versus 9 months respectively. Severe toxicity include grade 3-4 leukopenia (4% versus 2%), neutropenia (20% versus 22%) , anemia (38% versus 34%), thrombocytopenia (18% versus 24%), neurotoxicity (2% versus 6%) with DD and DP, respectively.&#x0D; Conclusion: The DD and DP regimens have similar efficacy but different toxicity. Either regimen can be used as front- line treatment of ABC. But in case of ED and EP regimen was difficult to compare the result due to very small sample size.&#x0D; Keywords: Epirubicin, doxorubicin, docetaxel, paclitaxel, advanced breast cancer, chemotherapy, neurotoxicity.

Cost-effectiveness of ribociclib plus letrozole versus palbociclib plus letrozole or letrozole as monotherapy in first-line treatment of postmenopausal women with HR+/HER2- locally advanced or metastatic breast cancer: a Brazilian private payer perspective.

Background:The global burden of breast cancer (BC) is high, especially in advanced stages. CDK 4/6 inhibitors represent a paradigm shift in the treatment of advanced BC HR+/HER2−, given the clinically and statistically significant gain in overall survival associated with this new class of medications. Nevertheless, as an innovation, the incorporation of these drugs impacts healthcare budgets, requiring cost-effectiveness analyses for decision-making. The aim of this study was to evaluate the cost-effectiveness of ribociclib plus letrozole compared with palbociclib plus letrozole or letrozole as monotherapy for first-line treatment of postmenopausal women with HR+/HER2− locally advanced or metastatic BC (aBC) from a Brazilian private healthcare system perspective.Methods:A model including progression-free survival (PFS), progressed disease, and death health states was used to simulate lifetime costs and outcomes. PFS and overall survival were derived from the MONALEESA-2 trial (lifetime horizon). Healthcare costs included drug acquisition and monitoring, subsequent therapies, adverse events, and end-of-life costs. Effectiveness was measured in quality-adjusted life-years (QALYs). Deterministic and probabilistic sensitivity analyses were performed.Results:The total cost of treatment with ribociclib plus letrozole was USD 72,091.82 versus USD 92,749.64 for palbociclib plus letrozole. Total QALYs were 3.30 and 3.16, respectively. Base-case analysis showed ribociclib as dominant over palbociclib in first-line treatment of women with HR+/HER2− aBC, associated with cost savings and QALY gains. The total cost of treatment with ribociclib plus letrozole was USD 83,058.73 versus USD 29,215.10 for letrozole. Total QALYs were 3.84 and 2.61, respectively. Compared with letrozole, ribociclib plus letrozole was associated with an incremental cost of USD 53,843.64 and an incremental QALY gain of 1.23, with incremental cost-effectiveness ratio of USD 43,826.91 per QALY gained.Conclusions:As demonstrated by the cost-effectiveness dominance over palbociclib, ribociclib results in savings when used as first-line treatment in postmenopausal women with HR+/HER2− aBC, warranting incorporation in the private healthcare system.

Group Physiotherapy for Treatment of Pelvic Floor Dysfunction: A Consumer’s Perspective

Introduction: Level 1 grade A evidence exists to support physiotherapy as a first line treatment of women with stress urinary incontinence and pelvic organ prolapse (POP). A novel way to provide care for women with pelvic floor dysfunction in a tertiary hospital setting is to mandate attendance at an introductory group education session prior to offering an individual physiotherapy consultation. There is minimal research to date examining the consumer perspective of group physiotherapy for treatment of pelvic floor dysfunction. This study aims to evaluate the consumer experience with a view to determining if this model of care meets the needs and expectations of the consumer. Objective: To evaluate the consumer perspective of an educational and practical pelvic floor class prior to offering an individual physiotherapy appointment for women with pelvic floor dysfunction. Method: Over a 6-month period, 39 women completed a voluntary, anonymous survey to evaluate their experience of attending a physiotherapy pelvic floor class. Results: Respondents reported that the information delivered was appropriate, relevant, and engaging and felt more informed and less alone in their symptoms after attending the pelvic floor class. Women reported that they had received the necessary education and practical skills required to begin implementing practical changes that addressed their pelvic floor dysfunction. Conclusion: By providing a consistent, informative, and practical group session for women referred with pelvic floor dysfunction as a baseline entry point to individual care, treatment can be commenced that is acceptable to the consumer. The acceptability of this method of service delivery serves as a basis for further important research evaluating the efficiency and effectiveness of group physiotherapy treatment.