Hormone Therapy Research Articles

[Efficacy analysis of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 inhibitor treatment in hormone receptor positive/human epidermal growth factor receptor 2-low metastatic breast cancer].

Objective: To evaluate the efficacy of chemotherapy and endocrine therapy combined with targeted drugs after progression on cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment in hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer. Methods: Patients with metastatic breast cancer diagnosed with HR positive/HER2 low expression at the Fifth Medical Center of PLA General Hospital from October 1, 2018 to September 30, 2023 were retrospectively included. All patients received sequential chemotherapy or sequential endocrine therapy combined with targeted drugs after progression on CDK4/6 inhibitor treatment.The median follow-up was 9 months, and the follow-up ended on October 31, 2023. The patients were divided into chemotherapy group (receiving sequential chemotherapy) and endocrine therapy group (receiving sequential endocrine therapy combined with targeted drugs), according to the treatment plan. Information on demographic data, clinical and pathological diagnosis, treatment regimen, and efficacy evaluation was collected. The basic conditions of patients who may affect the curative effect of different treatment schemes were preset as stratified subgroups, including age, progesterone receptor (PR) status, HER2 status, disease-free survival, number of previous endocrine therapy and chemotherapy, and visceral metastasis. The primary endpoint was progression-free survival (PFS), the secondary endpoints were objective response rate (ORR), clinical benefit rate(CBR) and PFS based on stratification factors. The survival curve was plotted by Kaplan-Meier method, the comparison of PFS between groups was performed by log-rank test, and the comparison of ORR and CBR between groups were performed by χ2 test. Results: A total of 188 patients were included, including 126 patients in the chemotherapy group [all females, aged 29-74 (51±10) years] and 62 patients in the endocrine therapy group [1 male and 61 female, aged 29-77 (51±12) years]. ORR of chemotherapy group was 23.0% (29/126), higher than that of endocrine treatment group [3.2% (2/62)] (P<0.001); The CBR of chemotherapy group and endocrine therapy group were 46.8% (59/126) and 33.9% (21/62), respectively, with no statistical significance (P=0.091). The median PFS of chemotherapy group and endocrine therapy group were 5.0 (95%CI: 4.3-5.7) and 4.0 (95%CI: 1.6-6.4) months, respectively, with no statistical significance (P=0.484). In the preset stratified subgroups, the median PFS of chemotherapy [6.0 (95%CI: 5.4-6.6) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 1.8-2.2) months] (P<0.001) in PR negative patients; In patients who had progressed on over 2 previous endocrine treatments, the median PFS of chemotherapy [5.0 (95%CI: 3.8-6.2) months] was longer than that of endocrine combined with targeted therapy [2.0 (95%CI: 0.6-3.4) months] (P=0.045). Conclusions: After progression on treatment with CDK4/6 inhibitors for HR-positive/HER2-low expression metastatic breast cancer, both chemotherapy and endocrine therpy combined with targeted drugs are viable treatment options. However, for patients with PR negative or ≥2 lines of endocrine therapy previously, priority should be accorded to chemotherapy.

CDK4/6 inhibitors: The Devil is in the Detail.

Update on the most recent clinical evidence on CDK4/6 inhibitors (CDK4/6i) in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer. Over the past decade, CDK4/6i have become part of the standard of care treatment of patients with both metastatic and high-risk early HR + /HER2- breast cancers. The three available CDK4/6i (palbociclib, ribociclib and abemaciclib) have been extensively studied in combination with endocrine therapy (ET) in metastatic breast cancer (mBC) with consistent prolongation of progression free survival; however, ribociclib has emerged as the preferred first line agent in mBC given overall survival benefit over endocrine monotherapy. In early BC, abemaciclib is the only currently approved agent while ribociclib has early positive clinical trial data. Toxicities and financial burden limit the use of CDK4/6i in all patients and resource-poor settings, and optimal timing of their use in mBC remains unclear. There is considerable evidence for the use of CDK4/6i in metastatic and early HR + /HER2- breast cancer, but knowledge gaps remain, and further research is necessary to better define their optimal use.

A CARM1 Inhibitor Potently Suppresses Breast Cancer Both In Vitro and In Vivo.

CARM1, belonging to the protein arginine methyltransferase (PRMT) family, is intricately associated with the progression of cancer and is viewed as a promising target for both cancer diagnosis and therapy. However, the number of specific and potent CARM1 inhibitors is limited. We herein discovered a CARM1 inhibitor, iCARM1, that showed better specificity and activity toward CARM1 compared to the known CARM1 inhibitors, EZM2302 and TP-064. Similar to CARM1 knockdown, iCARM1 suppressed the expression of oncogenic estrogen/ERα-target genes, whereas activated type I interferon (IFN) and IFN-induced genes (ISGs) in breast cancer cells. Consequently, iCARM1 potently suppressed breast cancer cell growth both in vitro and in vivo. The combination of iCARM1 with either endocrine therapy drugs or etoposide demonstrated synergistic effects in inhibiting the growth of breast tumors. In summary, targeting CARM1 by iCARM1 effectively suppresses breast tumor growth, offering a promising therapeutic approach for managing breast cancers in clinical settings.

Phase III Randomized, Placebo-Controlled Clinical Trial of Donepezil for Treatment of Cognitive Impairment in Breast Cancer Survivors After Adjuvant Chemotherapy (WF-97116).

To test efficacy of donepezil, a cognitive enhancer, to improve memory in breast cancer survivors who report cancer-related cognitive impairment 1-5 years postchemotherapy. Adult female BCS exposed to ≥4 cycles of adjuvant chemotherapy 1-5 years before enrollment who reported cancer-related cognitive impairment were eligible. Participants, enrolled at sites affiliated with the Wake Forest NCI Community Oncology Research Program (NCORP) Research Base, were randomly assigned to receive 5 mg of donepezil once daily for 6 weeks titrated to 10 mg once daily for 18 weeks or placebo. Cognition and self-report cognitive functioning was assessed at baseline, 12, 24 (end of intervention), and 36 (washout) weeks postrandomization. Mixed-effects repeated measures analysis of covariance models were used to assess treatment differences in immediate recall (primary outcome) on the Hopkins Verbal Learning Test-Revised (HVLT-R) and other cognitive domains (secondary outcomes) with covariates of treatment, time, time by treatment interaction, baseline outcome level, age stratification, and an unstructured covariance matrix to account for within participant correlation over time. Two hundred seventy-six BCS from 87 NCORP practices (mean age, 57.1, standard deviation [SD], 10.5) who were at a mean of 29.6 months (SD, 14.2) postchemotherapy were randomly assigned to donepezil (n = 140) or placebo (n = 136). At 24 weeks, treatment groups did not differ on HVLT-R scores (donepezil mean = 25.98, placebo = 26.50, P = .32). There were no statistically significant differences between treatments at 12, 24, or 36 weeks for attention, executive function, verbal fluency, processing speed, or self-reported cognitive functioning. Endocrine therapy and menopausal status did not affect results. BCS 1-5 years after completing chemotherapy with documented memory problems, randomly assigned to 24 weeks of 5-10 mg of donepezil once daily, did not perform differently at the end of treatment on tests of memory, other cognitive functions, or subjective functioning than those randomly assigned to placebo.

Inflammatory Rheumatic Disorders as a Complication of Endocrine Therapy for Breast Cancer

Inflammatory Rheumatic Disorders as a Complication of Endocrine Therapy for Breast Cancer

Novel Pyrazole-Chalcone Hybrids: Synthesis and Computational Insights Against Breast Cancer.

More women die of breast cancer than of any other malignancy. The resistance and toxicity of traditional hormone therapy created an urgent need for potential molecules for treating breast cancer effectively. Novel biphenyl-substituted pyrazole chalcones linked to a pyrrolidine ring were designed by using a hybridization approach. The hybrids were assessed against MCF-7 and MDA-MB-231 cells by NRU assay. Among them, 8k, 8d, 8m, 8h, and 8f showed significantly potent IC50 values: 0.17, 5.48, 8.13, 20.51, and 23.61 µM) respectively, on MCF-7 cells compared to the positive control Raloxifene and Tamoxifen. Furthermore, most active compound 8k [3-(3-(4-fluorophenyl)-1-phenyl-1H-pyrazol-4-yl)-1-(2-(2-(pyrrolidin-1-yl)-ethoxy)-phenyl)-chalcone] showed cell death induced through apoptosis, cell cycle arrest at the G2/M phase, and demonstrated decrease of ER-α protein in western blotting study. Docking studies of 8k and 8d established adequate interactions with estrogen receptor-α as required for SERM binding. The active hybrids exhibited good pharmacokinetic properties for oral bioavailability and drug-likeness. Whereas, RMSD, RMSF, and Rg values from Molecular dynamics studies stipulated stability of the complex formed between compound 8k and receptor. All of these findings strongly indicate the antiproliferative potential of pyrazole-chalcone hybrids for the treatment of breast cancer.

Everolimus plus endocrine therapy beyond CDK4/6 inhibitors progression for HR+ /HER2- advanced breast cancer: a real-world evidence cohort.

Everolimus in combination with endocrine therapy (ET) was formerly approved as 2nd-line therapy in HR(+)/HER2(-) advanced breast cancer (aBC) patients (pts) progressing during or after a non-steroidal aromatase inhibitor (NSAI). Since this approval, the treatment landscape of aBC has changed dramatically, particularly with the arrival of CDK 4-6 inhibitors. Endocrine monotherapy after progression to CDK4/6 inhibitors has shown a limited progression-free survival (PFS), below 3months. Evidence of the efficacy of everolimus plus ET after CDK4/6 inhibitors is scarce. A retrospective observational study of patients with aBC treated with everolimus and ET beyond CDK4/6-i progression compiled from February 2015 to December 2022 in 4 Spanish hospitals was performed. Clinical and demographic data were collected from medical records. The main objective was to estimate the median progression-free survival (mPFS). Everolimus adverse events (AE) were registered. Quantitative variables were summarized with medians; qualitative variables with proportions and the Kaplan-Meier method were used for survival estimates. One hundred sixty-one patients received everolimus plus ET (exemestane: 96, fulvestrant: 54, tamoxifen: 10, unknown: 1) after progressing on a CDK4/6 inhibitor. The median follow-up time was 15months (interquartile range: 1-56months). The median age at diagnosis was 49years (range: 35-90years). The estimated mPFS was 6.0months (95%CI 5.3-7.8months). PFS was longer in patients with previous CDK4/6 inhibitor therapy lasting for > 18months (8.7months, 95%CI 6.6-11.3months), in patients w/o visceral metastases (8.0months, 95%CI 5.8-10.5months), and chemotherapy-naïve in the metastatic setting (7.2months, 95%CI 5.9-8.4months). This retrospective analysis cohort of everolimus plus ET in mBC patients previously treated with a CDK4/6 inhibitor suggests a longer estimated mPFS when compared with the mPFS with ET monotherapy obtained from current randomized clinical data. Everolimus plus ET may be considered as a valid control arm in novel clinical trial designs.

Effect of young age (below 40 years) on oncologic outcomes in Lebanese patients with breast cancer: a matched cohort study

BackgroundDeveloping countries have a significantly higher incidence of breast cancer in patients younger than 40 years as compared to developed countries. This study aimed to examine if young age at diagnosis is an independent prognostic factor for worse survival outcomes in breast cancer as well as the effect of age on Disease-free survival (DFS) and local recurrence free survival (LRFS) after adjusting for various tumor characteristics, local and systemic treatments.MethodsThis is a secondary analysis of prospective cohort of patients from two existing databases. We identified patients with breast cancer aged 40 years or less and we matched them to those older than 40 years. We also matched based on stage and molecular subtypes. In cohort 1, we matched at a ratio of 1:1, while in cohort 2 we matched at a ratio of 1:3.ResultsIn cohort 1, Disease-free survival (DFS) at 5 years was significantly shorter for those younger than 40 years (75.6% and 92.7% respectively; p < 0.03). On multivariate analysis, only chemotherapy was found to be significant, while age was not found to be an independent predictor of prognosis. Local recurrence free survival at 5 years was similar between both age categories. Only hormonal therapy is a significant predictor for LRFS at 5 years. In the second cohort, DFS and LRFS at 3 years were similar between those younger and those older than 40 years. On multivariate analysis, no factor including age was found to be an independent predictor of prognosis.ConclusionData in the literature is controversial on the effect of young age on breast cancer prognosis. Our findings could not demonstrate that age is an independent prognostic factor in our population. There is a need for outcomes from larger, prospective series that have longer follow-ups and more data from our region.

Pilot randomized controlled trial of a program to enhance experience and adherence with adjuvant endocrine therapy among women with non-metastatic breast cancer: 12-month quantitative results.

Adjuvant endocrine therapy (AET) reduces recurrence risk after hormone receptor-positive breast cancer, but non-adherence is common. We pilot-tested SOIE, a program to enhance AET experience and adherence, to assess its acceptability, feasibility, and effects on psychosocial precursors of AET adherence. We conducted a 12-month pilot randomized controlled trial among women who had a first AET prescription. Intervention group received SOIE while control group received usual care. Psychosocial factors from the Theory of Planned Behavior (TPB) (intention-primary outcome-, attitude, subjective norm, behavioral control), additional constructs (AET knowledge, social support, coping planning), impact of AET services received, and adherence were measured by questionnaires at baseline, 3-month, and 12-month endpoints. Group patterns were compared using repeated measures analyses with generalized estimating equations. A total of 106 women were randomized (participation = 54.9%; intervention n = 52; control n = 54; retention = 93.8%). Among SOIE women, ≥ 90% received the program components and were satisfied. Both groups scored high on adherence intentions and group patterns over time were not statistically different. In the intervention group, AET knowledge and coping planning with side effects increased (group-by-time p-value = .002 and .016), a higher proportion reported that AET services received helped them take their AET (p < .05) and have a consistent daily intake (p = .01). SOIE is feasible and acceptable for survivors with an AET. SOIE did not significantly impact adherence intentions but was beneficial for other program outcomes and daily intake. SOIE may represent an encouraging avenue to enhance supportive care and empower survivors with managing AET.

Impact of the COVID-19 pandemic on breast cancer patient pathways and outcomes in the United Kingdom and the Republic of Ireland - a scoping review.

The COVID-19 pandemic brought unplanned service disruption for breast cancer diagnostic, treatment and support services. This scoping review describes these changes and their impact in the UK and the Republic of Ireland based on studies published between January 2020 and August 2023. Thirty-four of 569 papers were included. Data were extracted and results thematically organized. Findings include fewer new cases; stage shift (fewer early- and more late-stage disease); and changes to healthcare organization, breast screening and treatment. Examples are accepting fewer referrals, applying stricter referral criteria and relying more on virtual consultations and multi-disciplinary meetings. Screening service programs paused during the pandemic before enacting risk-based phased restarts with longer appointment times to accommodate reduced staffing numbers and enhanced infection-control regimes. Treatments shifted from predominantly conventional to hypofractionated radiotherapy, fewer surgical procedures and increased use of bridging endocrine therapy. The long-term impact of such changes are unknown so definitive guidelines for future emergencies are not yet available. Cancer registries, with their large sample sizes and population coverage, are well placed to monitor changes to stage and survival despite difficulties obtaining definitive staging during diagnosis because surgery and pathological assessments are delayed. Multisite longitudinal studies can also provide guidance for future disaster preparedness.

Estrogen Signals through ERβ in Breast Cancer; What We Have Learned since the Discovery of the Receptor

Estrogen receptor (ER) β (ERβ) is the second ER subtype that mediates the effects of estrogen in target tissues along with ERα that represents a validated biomarker and target for endocrine therapy in breast cancer. ERα was the only known ER subtype until 1996 when the discovery of ERβ opened a new chapter in endocrinology and prompted a thorough reevaluation of the estrogen signaling paradigm. Unlike the oncogenic ERα, ERβ has been proposed to function as a tumor suppressor in breast cancer, and extensive research is underway to uncover the full spectrum of ERβ activities and elucidate its mechanism of action. Recent studies have relied on new transgenic models to capture effects in normal and malignant breast that were not previously detected. They have also benefited from the development of highly specific synthetic ligands that are used to demonstrate distinct mechanisms of gene regulation in cancer. As a result, significant new information about the biology and clinical importance of ERβ is now available, which is the focus of discussion in the present article.

HEALTH-RELATED QUALITY OF LIFE IN POSTMENOPAUSAL WOMEN WITH ADVANCED BREAST CANCER RECEIVING ADJUVANT HORMONE THERAPY (RIBOCICLIB AND LETROZOLE)

Breast cancer is a type of cancer that affects many women in Indonesia. Adjuvant hormone therapies, such as letrozole and ribociclib, have succeeded in improving the patient's quality of life. This study aimed to assess the quality of life of postmenopausal women with advanced breast cancer who received adjuvant hormone therapy with ribociclib and letrozole. A cross-sectional study was conducted using retrospective data from postmenopausal female breast cancer patients at Dharmais Cancer Hospital between 2020 and 2023 who met the inclusion criteria. To determine the impact of sociodemographics on patient quality of life, data were examined using the quality of life score (EQ5D5L) and Spearman test. There were 29 patients, with a mean age of 54.9 years (SD = 8.65); the highest education level was high school (34.5%); The majority of occupations are housewives (69%), and the majority are stage IV (34.5%). The mean utility and VAS values of Ribociclib were 0.885 and 81.66, respectively, whereas those for letrozole were 0.725 and 78.46, respectively. Analysis of the relationship between quality of life and patient characteristics showed that the quality of life of patients with breast cancer treated with adjuvant ribociclib and letrozole therapy was influenced by the stage of breast cancer (p = 0.008). These findings indicate that patients receiving ribociclib and letrozole therapy have a good quality of life, which quality of life quality of life is influenced by the stage of malignancy.  Keywords: breast cancer, quality of life, letrozole, ribociclib, post menopause

Abstract PS02-01: Efficacy, safety, and quality of life with ribociclib + endocrine therapy in elderly patients with HR+/HER2– advanced breast cancer across the MONALEESA-2, -3, and -7 trials

Abstract Background: Ribociclib (RIB) + endocrine therapy (ET) showed statistically significant progression-free survival (PFS) and overall survival (OS) benefits in MONALEESA-2, -3, and -7 in patients (pts) with HR+/HER2− advanced breast cancer (ABC). Here, we report efficacy, safety, and quality of life (QOL) with RIB + ET in elderly pts in the MONALEESA trials. Methods: Data were pooled from the MONALEESA-2, -3, and -7 trials of pre- and postmenopausal pts with HR+/HER2− ABC treated with first-line RIB + ET or placebo (PBO) + ET. The tamoxifen cohort in MONALEESA-7 and pts with early relapse were excluded from this analysis. PFS, OS, and time to first chemotherapy (TTC) were analyzed in pts &amp;lt;65 y, 65- &amp;lt;75 y, and ≥75 y using Kaplan-Meier methods. Time to definitive deterioration (TTD) by ≥10 points in global health status (GHS) was analyzed across age subgroups using Kaplan-Meier methods. Results: Of the 1229 pts included in this analysis, 773 (62.9%) were &amp;lt;65 y, 335 (27.3%) were 65- &amp;lt;75 y, and 121 (9.8%) were ≥75 y. There were minor differences in baseline characteristics between the age groups: slightly higher % of pts in the ≥75 y group with a ECOG status of 1 and slightly higher % of de novo disease in the &amp;lt;65 y group (Table). Regardless of age, a PFS and OS benefit was seen with RIB + ET vs PBO + ET (Table). RIB + ET also delayed the median TTC in all age groups. In the RIB + ET group, the most common first subsequent antineoplastic treatment was hormonal therapy alone ( &amp;lt;65 y, 26.3%; 65- &amp;lt;75 y, 41.6%; ≥75 y, 38.1%). In the ≥75 y subgroup, pts in the RIB + ET arm (6.3%) less frequently used chemotherapy alone as the first subsequent antineoplastic treatment vs the PBO + ET (24.5%) arm. In pts &amp;lt;65 y, safety results were consistent with those in the overall trial population. In pts 65- &amp;lt;75 y and ≥75 y, the most common any grade adverse events (AEs) with RIB + ET vs PBO + ET were neutropenia (67.6% vs 5.4% and 52.9% vs 3.8%), nausea (52.7% vs 32.0% and 52.9% vs 40.4%), fatigue (42.0% vs 38.1% and 36.8% vs 21.2%), and diarrhea (39.9% vs 30.6% and 48.5% vs 32.7%). For RIB + ET vs PBO + ET, rates of grade 3/4 febrile neutropenia ( &amp;lt;65 y, 1.2% vs 0.3%; 65- &amp;lt;75 y, 1.1% vs 0; ≥75 y, 2.9% vs 0), all grade interstitial lung disease ( &amp;lt;65 y, 1.0% vs 0.6%; 65- &amp;lt;75 y, 2.7% vs 0.7%; ≥75 y, 7.4% vs 0), and all grade QT prolongation ( &amp;lt;65 y, 9.1% vs 2.9%; 65- &amp;lt;75 y, 11.2% vs 4.1%; ≥75 y, 16.2% vs 1.9%) were numerically higher in pts 65- &amp;lt;75 y and ≥75 y than in pts &amp;lt;65 y. Rates of discontinuation due to AEs with RIB + ET vs PBO + ET were 14.6% vs 3.1% in pts &amp;lt;65 y, 19.7% vs 6.8% in pts 65- &amp;lt;75 y, and 41.2% vs 7.7% in pts ≥75 y. In pts who discontinued treatment due to AEs, the percentage of pts without prior dose reduction was 34.4% in pts &amp;lt;65 y, 40.5% in pts 65- &amp;lt;75 y, and 50.0% in pts ≥75 y. TTD in GHS was prolonged with RIB + ET vs PBO + ET in pts &amp;lt;65 y. In pts 65- &amp;lt;75 y and ≥75 y, TTD was generally similar with RIB + ET vs PBO + ET (Table). Conclusions: This pooled analysis of the MONALEESA-2, -3, and -7 trials demonstrated PFS and OS benefits with RIB + ET in elderly pts consistent with those observed in younger pts. Across age subgroups, treatment with RIB + ET also delayed TTC. Overall, RIB was well tolerated in elderly pts, with a safety profile consistent with what is anticipated for an older patient population. Additionally, there was no difference in TTD in GHS with RIB + ET vs PBO + ET in pts 65- &amp;lt;75 y and pts ≥75 y. Citation Format: Lowell Hart, Seock-Ah Im, Sara Tolaney, Mario Campone, Timothy Pluard, Berta Sousa, Gilles Freyer, Thomas Decker, Kevin Kalinsky, Astrid Thuerigen, Melissa Gao, Huilin Hu, Sherko Küemmel. Efficacy, safety, and quality of life with ribociclib + endocrine therapy in elderly patients with HR+/HER2– advanced breast cancer across the MONALEESA-2, -3, and -7 trials [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS02-01.

Abstract PO4-01-09: The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer

Abstract Backgrounds: We previously reported an analysis of the impact of adjuvant endocrine therapy (ET) for patients with ER+ and HER2- T1a/bN0M0 breast cancer (BC) at ASCO 2023 (Abstract #538). For the whole cohort, adjuvant ET significantly reduced distant metastases, but the absolute overall survival (OS) difference was small. The presence of medical comorbidities related to treatment toxicity and the estimated life-expectancy differ based on age, affecting the clinical impact of ET. There may be settings where comorbidities result in a sufficiently short, expected OS such that the benefit of ET will not outweigh risk. In multivariate analysis, age (&amp;lt;55 vs &amp;gt;55) was not an independent risk factor for distant metastasis. Here we evaluate the impact of adjuvant ET for ER+/HER2- T1a/bN0M0 breast cancer by age-specific subgroups, focusing on younger (&amp;lt; 40) and older (&amp;gt;65) population. Methods: This is a multicenter retrospective cohort study that evaluated the impact of adjuvant ET for patents with ER+/HER2- T1a/bN0M0 BC who underwent primary breast cancer surgery between 2008 and 2012 in 47 institutes of the Japan Clinical Oncology Group (JCOG). We analyzed distant metastatic-free survival (DMFS) and OS using Kaplan-Meier estimates with log-rank test in patients treated with and without ET in each of three age-specific subgroups (&amp;lt;40, 41-64 and 65&amp;gt; years of age). Results: Median follow-up was 9.2 years; the median age of the entire cohort was 55 years. Of 4756 eligible patients, 417 patients were age 65 (1025 (82%) with ET and 227 (18%) without ET). Of all 3989 (84%) patients with ET (2053 (51%) with Tamoxifen, 2142 (54%) with Aromatase inhibitor, 595 (15%) with LH-RH analog and 76 (2%) with others, includes duplicates). In the &amp;lt; 40 subgroup, 9-year DMFS was 97.2% with ET and 91.0% without ET (p=0.023) and 9-year OS was 97.8% with ET and 97.0% without ET (p=0.954). In the &amp;gt; 65 subgroup), 9-year DMFS was 92.6% with ET and 84.0% without ET (p&amp;lt; 0.01) and 9-year OS was 93.8% with ET and 84.9% without ET (p&amp;lt; 0.01). In those aged 41-64, no significant difference was observed in both 9-year DMFS and OS between patients with and without ET (p=0.328 and p=0.731, respectively) See Table for details. Conclusions: Adjuvant endocrine therapy was associated with improved distant metastatic-free survival in the younger (&amp;lt;40) and older (&amp;gt;65) population in this large Japanese dataset and was associated with improved overall survival in those &amp;gt;65. Our findings suggest clinically relevant benefit from ET in both younger and older unselected patients with very small ER+ BC. The lack of benefit in patients aged 41-64 is likely due to individual tumor and treatment factors, which will be evaluated and described in detail at the meeting. Table. The 9-year DMFS and OS of each age-specific three subgroups. *They are analyzed by using Kaplan-Meier estimates with log-rank test between patients treated with and without ET. Citation Format: Yuko Takahashi, Shinsuke Sasada, Naoto Kondo, Hiroya Hashimoto, Kaori Terata, Kumiko Kida, Yasuaki Sagara, Yoichi Naito, Keisei Anan, Takayuki Ueno, Akihiko Suto, Chizuko Kanbayashi, Mina Takahashi, Rikiya Nakamura, Toshiyuki Ishiba, Michiko Tsuneizumi, Seiichiro Nishimura, Yukinori Ozaki, Akihiko Shimomura, Takehiko Sakai, Tsuguo Iwatani, Hideo Shigematsu, Kenji Tamura, Tomomi Fujisawa, Takashi Hojo, Fumitaka Hara, Tadahiko Shien, Hiroji Iwata. The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-09.

Abstract PO2-17-01: Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational study

Abstract Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the established first-line targeted therapy (TT) for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2–) advanced breast cancer (ABC). TreatER+ight, the first prospective, real-world study evaluating the treatment patterns, safety and effectiveness of ET alone or ET + TT in Canadian patients with HR+, HER2– ABC (2016 to 2020) recorded ET as the standard of care (SOC) in the first interim analysis report. However, treatment with CDK4/6i combined with ET have rapidly evolved as the SOC in the metastatic setting. Methods: This prospective, multicenter, observational study (NCT02753686) enrolled patients with HR+, HER2‒ ABC with or without prior exposure to ET and up to one line of prior CT in the advanced setting. The patients were enrolled by the line of their therapy (first-line, second-line or third-line) and grouped into 2 cohorts (ET and ET + TT). Duration of therapy, and overall survival (OS) are estimated using Kaplan–Meier method. Here, we report the final outcome with CDK4/6i treatment evolution with sequencing strategy and duration in routine clinical practice. Results: At data cutoff (December 1, 2022), a total of 439 enrolled patients (ET, n=104; ET + TT, n=335) from 25 centers in Canada, constituted the full analysis set. The median age (range) was 71.5 (37.0–96.0) years in ET cohort and 65.0 (23.0-87.0) years in ET + TT cohort. About 84.6% and 66.4% were postmenopausal patients in the ET and ET + TT cohorts, respectively. Patients with ECOG PS scores 0 to 1 composed of 82.0% and 93.5% in the ET and ET + TT cohorts, respectively. In the overall population, ET alone and ET + CDK4/6i were the most common treatment received by patients in first-line (43.5% and 43.3%) and second-line (36.3% and 24.6%) treatment settings. In third-line treatment setting, CT was the most common treatment received by patients (38.4%). Conclusions: Data from final analysis of TreatER+ight have further confirmed the evolution to primary use of CDK4/6i-based combination therapy in the first-line setting for Canadian patients with HR+, HER2– ABC. Additional details on duration of therapy by CDK4/6i agents, overall survival data and age subgroup analysis will be presented at SABCS 2023 Table 1_Baseline characteristics, treatment patterns, and duration of treatment Citation Format: Catherine Doyle, Ana Elisa Lohmann, Nayyer Iqbal, Jan-Willem Henning, Swati Kulkarni, Nadia Califaretti, John Hilton, Cristiano Ferrario, Nathaniel Bouganim, Mihaela Mates, Stephanie Guillemette, Ricardo Leite, Stephen Chia. Impact of the introduction of CDK4/6 inhibitors on treatment duration in patients with HR+, HER2– advanced breast cancer: Final analysis of TreatER+ight, a Canadian prospective, real-world, observational study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-17-01.

Abstract PO3-11-12: A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study)

Abstract Background. Interventions to improve tolerability and adherence to endocrine therapy (ET) are critical to the global improvement of breast cancer (BC) survivorship. The optimal time of day to take ET in terms of quality of life, side effects and adherence is unknown. This study compared a morning dose versus an evening dose of ET in patients with early-stage BC (EBC). Methods. In this pragmatic, open-label, multicenter trial, patients with hormone receptor-positive (HR+) EBC were randomized (1:1) to receive either a morning dose (within 1 hour of the patient wake up time) or an evening dose of ET (within 1 hour of patient bedtime). The primary endpoint was endocrine toxicity/tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline (commencement of ET) to 12 weeks. The secondary endpoints included: ET toxicity/tolerability and quality of life (FACT-ES and FACT-B) from baseline to 4, 8, 12 and 52 weeks, non-persistence or non-adherence, and patient timing preference. Results. Between June 2021 and March 2022, 245 eligible patients were randomized, 122 to morning (122/245, 49.8%) and 123 to evening (123/245, 50.2%) dosing. Mean age was 61 [standard deviation (sd) 11.9], 181 patients (73.9%) were postmenopausal, 188 (76.7%) received tamoxifen, 58 (23.7%) received an aromatase inhibitor and 22 (9%) received luteinizing hormone-releasing hormone. The mean changes in the FACT-ES score from baseline to 12 weeks following the beginning of ET were -2.0 (sd=14.3) vs -5.4 (sd=16.8) in the morning vs evening arms respectively (Wilcoxon two-sample rank sum test p-value=0.22). Also, the proportion of patients with a clinically important increase (Fisher’s exact test p-value=0.54 0.89) or decrease (p-value= 0.89) in FACT-ES Scores was not statistically different between the arms. At 52 weeks, the mean changes in the FACT-ES score from baseline were -2.5 (sd=18.8) vs -4.8 (sd=15.5) in the morning vs evening arms respectively (p-value=0.23). There was no statistical difference in FACT-ES and FACT-B scores over the 52 weeks of the study. At 12 weeks, 94.5% (69/79) vs 98.7% (78/79) were still taking the ET (p-value=0.2), whereas at 52 weeks, 92.1% (58/63) vs 85.4% (41/48) were still taking ET (p-value=0.36), in the morning vs evening arms respectively. Also, 13.7% (10/73) vs 7.6% (6/79) and 3.2% (2/62) vs 12.5% (6/48) interrupted their ET at least once, in the morning vs evening arms, at 12 and 52 weeks respectively. At week 52, 57.9% (62/107) in the morning arm vs 13.5% (14/104) in the evening arm strongly preferred an ET morning dose, whereas 7.5% (8/107) vs 42.3% (44/104) strongly preferred an ET evening dose. No significant preference changes were observed in dose timing from baseline to week 52 (p-value=0.081). Conclusions. These results suggest no significant difference in quality of life or adherence if ET is taken in the morning or in the evening. Patients should be reassured that they can take ET at their preferred time. Clinical Trial Registration: NCT04864405 Table 1. Mean changes between FACT scores at 12 weeks and 52 weeks from baseline for patients receiving ET morning vs evening dose. A positive value indicates the FACT score increased over time. FACT ES: Endocrine Subscale; FACT B: breast Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Lesley Fallowfield, Terry Ng, Arif Awan, Sandeep Sehdev, Ana-Alicia Beltran-Bless, Mark Clemons. A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-12.

Abstract PO2-11-01: Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors

Abstract Background: Cardiovascular disease (CVD) and cancer are the two leading causes of death in the U.S, and breast cancer (BC) is the most common cancer among women. Most survivors of early-stage BC are prescribed adjuvant endocrine therapy (ET) to decrease their BC recurrence risk; many of them are also on statins and/or antihypertensives to manage concurrent CVD risk factors. Nonadherence to ET or CVD medications is associated with decreased survival and other poor outcomes, yet little is known about how best to identify nonadherence to multiple classes of medications in BC survivors. Methods: We reviewed pharmacy fill data from our electronic health record (EHR) for a diverse cohort of patients seen in our breast oncology clinic with prescriptions for ET and CVD medications (statin and/or antihypertensive(s)). Patients were excluded if their pharmacy data did not show both an active ET order and an active CVD order or fill. Nonadherence to any medication was defined as proportion of days covered (PDC) &amp;lt; 80% over the previous 180 days. A subset of patients also responded to a patient-reported nonadherence screener administered through our EHR at appointment registration starting in 2/2022. Descriptive statistics were used to determine the prevalence of nonadherence to all medications (defined as PDC&amp;lt; 80% for either ET and/or CVD medications) and for each class of medication separately. We also compared the PDC-based combined nonadherence to the self-reported nonadherence. Results: We identified a total of 1,015 BC survivors on ET and CVD medications last seen in clinic between 2/1/2020 and 6/6/2023 (mean age 69 yo; 23.6% non-Hispanic White, 11.3% non-Hispanic Black, and 38.9% Hispanic). Of these, 567 (55.9%) were prescribed ET and statins, and 745 (73.4%) were prescribed ET and antihypertensives. With nonadherence defined as PDC&amp;lt; 80% for any medication (ET and/or CVD medications), the nonadherence prevalence was 38.4%. The nonadherence prevalence by medication class was slightly lower for ET (20.7%) than for statins (25.9%) and antihypertensives (25.0%). Among patients on ET and statins, 10.1% were nonadherent to both medications and 24.3% were nonadherent to only 1 class of medications; the proportion of patients nonadherent to ET only was almost half that of patients nonadherent to statins only (8.5% vs 15.9%). A similar trend was observed among patients on ET and antihypertensives: 10.3% were nonadherent to both classes of medications and 26.2% were nonadherent to only 1 class of medications, with 11.5% of patients nonadherent to ET only and 14.6% nonadherent to antihypertensives only. Of the 1,015 patients, 390 (38.4%) responded to the nonadherence screener between 2/16/2022 and 6/6/2023, of which 93 (23.8%) reported any level of medication nonadherence. Among these, 57 (61.3%) had PDC≥ 80% and thus were categorized as adherent under our PDC-based adherence determination. Of the 297 patients who self-reported adherence to all medications on the screener, 32.3% had PDC&amp;lt; 80% for any medication. When combining nonadherence by PDC and self-report, the overall nonadherence rate for the 390 patients who responded to the screener was considerably higher at 48.5% (vs 33.8% by PDC only and 23.8% by self-report only). Conclusions: EHR-based screening can identify patients with or at risk for medication nonadherence for targeted interventions. Using a combined approach of pharmacy fill data and patient reports, close to 50% of patients were identified as having nonadherence to at least 1 medication. Nonadherence to statins and antihypertensives was more common than nonadherence to ET, which is concerning as early-stage BC survivors are more likely to die from CVD than BC. Interventions to improve adherence to multiple classes of medications are warranted in this population. Citation Format: Claire Sathe, David DeStephano, Shing Lee, Melissa Beauchemin, Nadia Liyanage-Don, Melissa Accordino, Katherine Crew, Ian Kronish, Dawn Hershman. Prevalence of Nonadherence to Endocrine Therapy and Cardiovascular Medications Among Breast Cancer Survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-11-01.

Abstract PO3-05-03: Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221)

Abstract Introduction: Endocrine therapy (ET) plus CDK 4/6 inhibitors is considered the standard of care as first-line therapy in hormone receptor positive (HR+)/HER2 negative (HER2-) metastatic breast cancer (mBC). Nonetheless, the use of chemotherapy (CT) is frequent in clinical practice, and access to CDK 4/6 inhibitors is limited in some countries. We used real-world data to describe treatment patterns, the impact of health insurance type, and outcomes among Brazilian patients with HR+/HER2- mBC treated in the first-line setting. Methods: In this observational retrospective study, female patients ≥ 18 years old diagnosed with de novo or recurrent HR+/HER2- mBC between January 2018 and December 2020 were included. Patients' data were extracted from medical charts or electronic health records (EHR). The primary endpoint was first-line treatment patterns in public and private health system cohorts. Key secondary endpoints were progression-free survival (PFS), defined as time from 1L treatment to progression or death, and overall survival (OS), defined as time from diagnosis of mBC until death or censoring. No formal statistical assumption was performed for sample size, the study recruited 2 cohorts of 150 patients from the public and 150 patients from the private health insurance system. Results: A total of 307 patients were included, 156 from public and 151 from private health insurance system, from 13 sites in Brazil. Median age was 56.8 (range 19.9-94.1), and 32.2% (N=99) had de novo MBC. Treatment patterns are described in Table 1. The most frequent treatment received in 1L was ET alone 42.4%, followed by CT (alone or CT followed by ET +- CDK4/6i) 31.6% and ET + CDK4/6i 25.1%. There was a significant difference between the 1L treatment with ET + CDK4/6i in the private and public systems, 48.3% vs 2.6%, p &amp;lt; .0001, respectively. The most frequently used CDK4/6i in 1L setting was Ribociclib (65.0%), followed by Palbociclib (36.9%) and Abemaciclib (7.1%). There was an increase in the use of CDK4/6i over time, 17% in 2018, 30.0% in 2019, and 27.9% in 2020. With a median follow-up of 32.2 months (95% CI: 29.4 - 34.4), the median 1L PFS was 22.9 months (95% CI: 16.9 - 25.2) in the public and 21.8 months (95% CI: 17.7 - 31.1) in the private health system, p=0.92. Median 1L PFS by treatment received was 13.6 months (95% CI: 6.1-39.0) with CT, 18.4 months (95% CI: 12.1-22.1) with CT followed by ET +-CDK4/6i, 21.9 months (95% CI: 17.3-25.5) with ET and 31.1 months with ET plus CDK 4/6i (95% CI: 15.8-42.8). Overall, median OS was 52.8 months (95%CI 49.4-NR). The 4-year OS rate per 1L treatment received were 50.3% (95% CI: 28.7-68.5) with CT, 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i, 74.4% (95% CI: 58.0-85.1) with ET alone, 71.3% (95% CI: 49.6-85.0) ET + CDK4/6i, 50.3% (95% CI: 28.7-68.5) with CT and 39.0% (95% CI: 13.9-63.8) CT followed by ET +- CDK4/6i. Conclusion: ET is the most commonly used 1L treatment in clinical practice in Brazil, followed by ET + CDK4/6i and CT. A large difference in CDK4/6i use was observed between private and public health systems, reflecting the current limited access to CDK4/6i in Brazil. This study highlights treatment disparities within a nation with a fragmented health insurance system. Table 1. Treatment Patterns in Public and Private Healthcare Systems Citation Format: Gustavo Werutsky, Daniela Rosa, Tomás Reinert, Romualdo Barroso-Sousa, Heloísa Resende, Poliana Signorini, Eduardo Cronenberger, Juliana Góes Martins Fagundes, Jorge Henrique Santos Leal, Marina Dutra Giffoni, Aline Vieira, Luiza Nardin Weis, Jose Marcio Figueiredo, Tatiana Correa, Fernando Castilho Venero, Luisa Mostardeiro Tabajara Franche, Marina Musse Bernardes, Rafaela Jesus, Gustavo Gössling, José Bines. Real-World Data on First-line Treatment of Hormone Receptor-positive, HER2-negative, Metastatic Breast Cancer in Brazil (BRAVE study - LACOG 0221) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-03.

Abstract PO1-17-12: The impact of treatment sequence of CDK4/6 inhibitor therapy on Metastatic Breast Cancer treatment outcomes in Real-World practice in U.S

Abstract Background A retrospective study to describe the actual benefit of treatment sequence with Endocrine Therapy (ET) plus cyclin D/cyclin-dependent kinases 4 and 6 (CDK4/6) therapy including as 1st-line and 2nd -line treatment for Metastatic breast cancer (MBC) patients with hormone receptor positive (HR+) and HER2 negative. We examined the extent that treatment sequence of CDK4/6 inhibitor therapy is associated with progression-free survival, and overall survival under real-world conditions. Methods This study used the nationwide electronic health record-derived-Flatiron Health de-identified database to estimate the real-world progression-free survival (rwPFS) and overall survival (rwOS) of MBC patients under different treatment sequence of CDK4/6 inhibitors. A total of 2,771 patients with ≥ 3 months of follow-up received either CDK4/6 inhibitor plus ET in the first-line setting (n=2,170) or ET alone in the first-line and CDK4/6 inhibitor plus ET in the second-line setting (n=601) between February 3, 2015, and November 02, 2021. We performed inverse probability weighting (IPW) to balance the baseline demographic and clinical characteristics between patients in the two groups. Kaplan-Meier method and Cox proportional hazards were used to test for an association of CDK4/6 treatment line sequence on PFS as the primary outcome and OS as the secondary outcome, adjusting for patient characteristics (e.g., age, race, comorbidities, ECOG value, Tumor site, and health insurance). Results Median follow-up was 25.6 months (interquartile range [IQR], 12.7–41.3) for the group with CDK4/6 inhibitor plus ET in first-line treatment and 33.1 months (IQR, 18.1–50.4) in those taking ET alone in first-line and CDK4/6 inhibitor plus ET in the second-line treatment. CDK4/6 inhibitor combination with ET as the first-line treatment was associated with significantly longer median rwPFS compared to receiving ET alone on first line and CDK4/6 inhibitor plus ET in the second line (28.0 vs 13.1 months; hazard ratio [HR], 0.40; 95% CI, 0.35–0.44; P &amp;lt; 0.0001). Median rwOS was 52 months for the group with first line CDK4/6 inhibitor plus ET and 48 months for the other group who received CDK4/6 inhibitor in the second line of treatment. However, the difference was not statistically significant (HR=0.91, 95% CI, 0.78–1.09, P-value=0.33). A propensity scores matching analysis showed similar results. Conclusions In this “real-world” population of patients with HR+/HER2− MBC, receiving CDK4/6 inhibitor plus ET as first line of treatment was associated with improved progression free survival compared with patients treated with ET alone in the first-line and CDK4/6 inhibitor plus ET on the second line of treatment. Citation Format: Gretchen Kimmick, Asal PIlehvari, Wen You, Gloribel Bonilla, Roger Anderson. The impact of treatment sequence of CDK4/6 inhibitor therapy on Metastatic Breast Cancer treatment outcomes in Real-World practice in U.S [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-17-12.

Abstract PO1-04-12: Palbociclib versus ribociclib in first-line treatment of patients with hormone-receptor positive HER2 negative advanced breast cancer – real world outcome data from the German registry platform OPAL

Abstract Introduction CDK4/6 inhibitors (CDKi) plus endocrine therapy (ET) are standard of care in first-line (1L) treatment of hormone receptor-positive (HR+) HER2-negative (HER2-) advanced breast cancer (ABC). In the pivotal trials the three CDK4/6i (palbociclib, ribociclib and abemaciclib) + ET showed similar progression-free survival (PFS) benefit over ET alone. However, other than ribociclib, palbociclib failed to demonstrate overall survival (OS) benefit. As patient (pts) characteristics differed between the trials, especially in the number of pts with treatment-free interval (TFI) of &amp;lt; 12 months after end of adjuvant ET, head-to-head comparisons of the CDKi are of clinical interest. Here we analyze the outcome of pts treated with palbociclib + ET or ribociclib + ET with real-world data from OPAL. Methods OPAL (NCT03417115) is a prospective observational, open, longitudinal multicenter cohort study (clinical registry) in Germany. Pts with ABC and early breast cancer can be recruited at start of their first systemic treatment. There are no treatment restrictions. Sites from all medical sectors can participate in OPAL (medical and gynecologic oncologists from outpatient centers and hospitals). Details on all (sequential) treatments, patient and tumor characteristics, biomarker testing, clinical and patient-reported outcomes are collected. Follow-Up is until death or up to 5 years. Between 01/2018 and 07/2021 1049 pts with HR+ HER2- ABC were recruited by 143 sites. Database cut was on 31/08/2022. 384 pts received palbociclib + ET and 231 pts received ribociclib + ET as 1L treatment. All endocrine combination partners including switch of ET during first line therapy was allowed, whereas switch of CDK4/6i (n=25) were excluded. PFS in registries can differ from PFS in clinical trials, since the RECIST criteria are usually not applied in routine care. PFS in registries represents the time to clinically relevant progression in routine care. PFS and OS were estimated using the Kaplan-Meier method. To adjust for confounding, inverse probability of treatment weighting (IPTW) by propensity score analysis was used to compare PFS and OS between 1L palbociclib+ET and ribociclib+ET. IPTW was performed for the following variables: age, menopausal status, ECOG, any comorbidity, Charlson comorbidity index, metastatic stage, type of metastasis, number of metastatic sites, estrogen-/progesterone status, IHC status, previous chemo-/endocrine therapy, kind of endocrine combination partner, disease-free interval, and treatment-free interval. Results From 2018 to 2021, the proportion of CDK4/6i increased from 68% to 86% in 1L of HR+HER2- ABC. Overall, palbociclib was used in 44% and ribociclib in 26% of all first-line treatments in OPAL. Median age of pts receiving palbociclib/ribociclib was 66/68 years and for 77/81% of pts at least one comorbidity was documented. 37/35% of pts already had metastasis at diagnosis (M1) and 25/26% of pts had a TFI &amp;lt; 12 months. After IPTW, the two treatment groups were comparable for all tested characteristics. 42/46% of patients had a progression (palbociclib/ribociclib group). IPTW-adjusted median PFS was 25.1 months (95% Confidence interval (CI) 20.1 – 30.1) for the palbociclib and 27.0 months (95%-CI 21.1 – 31.6) for the ribociclib group. Hazard ratio was 0.91 (0.71 – 1.17) for palbociclib versus ribociclib. 26/29% of patients had an OS event (palbociclib/ribociclib group). IPTW-adjusted median OS was 36.7 months (95%-CI 33.0 – NA) for the palbociclib and 36.6 months (95%-CI 33.1 – NA) for the ribociclib group. Hazard ratio was 0.95 (0.69 - 1.30) for palbociclib versus ribociclib. Conclusions This analysis of real word data in the OPAL registry platform showed similar PFS and OS for palbociclib + ET compared to ribociclib + ET, when adjusted for a wide range of potential confounding variables. Further analyses will investigate whether one drug showed favorable results in certain subgroups of pts. Citation Format: Marc Thill, Mark-Oliver Zahn, Anja Welt, Arnd Nusch, Matthias Zaiss, Kathrin Engelken, Gabriele Kaltenecker, Kai Ringwald, Katja Gratzke, Lisa Kruggel, Martina Jänicke, Holger Schulz, Christoph Losem, Volker Hagen, Roland Fricker, Elmar Stickeler, Nadia Harbeck, Achim Wöckel, Thomas Decker. Palbociclib versus ribociclib in first-line treatment of patients with hormone-receptor positive HER2 negative advanced breast cancer – real world outcome data from the German registry platform OPAL [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-04-12.