Endocrine Monotherapy Research Articles

Effectiveness of combined targeted and hormonal therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer: A systematic review and meta-analysis of RCTs.

we aim to synthesize available evidence on the effectiveness of hormonal plus targeted therapies for post-menopausal women with hormone receptor-positive and HER2-negative advanced breast cancer. We searched the following databases: Medline, PubMed, Cochrane Library, CINAHL, Web of Science, Scopus, and African Journal. Only studies that investigated the effectiveness of hormonal therapy combined with targeted therapy for HR+/HER2- advanced breast cancer treatment were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. Statistical analysis was performed using Comprehensive Meta-analysis version 3. 24 studies were included in the meta-analysis with an overall sample size of 7635. Median PFS, OS and ORR were found to be significantly increased in the combination group compared to hormonal monotherapy [SMD = 6.072 (95% CI = 3.785-8.360), p < 0.001], [SMD = 1.614 (95% CI = 0.139-3.089), p = 0.032] and [OR = 1.584 (CI 1.134-2.213), p = 0.007] respectively. Subgroup analysis showed a significant difference in PFS and ORR between patients who received "hormonal therapy + CDK4/6 inhibitors" vs hormonal therapy only [SMD = 6.015 (CI 3.069-8.960), p < 0.001], (OR = 1.828 (CI 1.030-3.243), p = 0.039] respectively. Compared with hormonal monotherapy, targeted plus hormonal therapy significantly improves PFS, OS and ORR in postmenopausal women with HR+/HER2- advanced breast cancer.

Complete response and long-term survival to endocrine monotherapy in a patient with metastatic breast cancer in a low-income country: a case report

BackgroundBreast cancer is the most common cancer in women. Progression-free survival for hormone receptor-positive/human epidermal growth factor receptor-2-negative metastatic breast cancer treated with endocrine therapy in combination with cyclin4/6-dependent kinase is approximately 25 months. This case represents metastatic breast cancer treated with endocrine therapy, leading to long-term survival.Case presentationA 40-year-old Syrian woman diagnosed with hormone receptor-negative breast cancer was treated surgically with adjuvant chemotherapy and radiotherapy. She developed local and nodal recurrences that were hormone receptor-positive, followed by a recurrence of malignant pleural effusion. She was initially treated with chemotherapy and then placed on endocrine therapy with a complete response from 2014 until now. The patient also suffered from adverse events of medications, such as heart failure and osteoporosis, which were treated appropriately.ConclusionThis case demonstrates a long-lasting complete response to metastatic breast cancer with malignant pleural effusion. This shows the validity of endocrine therapy in recurrent hormone receptor-positive breast cancer, especially in countries that cannot afford targeted therapies or genetic tests. It also highlights the necessity for a better understanding of the prognostic and predictive factors.

Oral minoxidil for late alopecia in cancer survivors.

Late alopecia, defined as incomplete hair regrowth > 6months following cytotoxic chemotherapy or > 6months from initiation of endocrine therapy, negatively impacts quality of life and may affect dose intensity of adjuvant therapy. This study investigates the effect of oral minoxidil in women with chemotherapy and/or endocrine therapy-induced late alopecia. The rate of clinical response was assessed by standardized photography and quantitated with trichoscopy. Two hundred and sixteen patients (mean age 57.8 ± 13.7) were included. The most common cancer diagnosis was breast, in 170 patients (79.1%). Alopecia developed after chemotherapy in 31 (14.4%) patients, endocrine monotherapy in 65 (30.1%) patients, and chemotherapy followed by endocrine therapy in 120 (55.6%) patients. In 119 patients, standardized photography assessments were used to determine clinical change in alopecia after a median of 105 (IQR = 70) days on oral minoxidil and revealed improvement in 88 (74%) patients. Forty-two patients received quantitative trichoscopic assessments at baseline and at follow-up after a median of 91 (IQR = 126) days on oral minoxidil. Patients had clinically and statistically significant increases in frontal hair shaft density (from 124.2 hairs/cm2 at initial to 153.2 hairs/cm2 at follow-up assessment, p = 0.008) and occipital shaft density (from 100.3 hairs/cm2 at initial to 123.5 hairs/cm2 at follow-up assessment. p = 0.004). No patients discontinued oral minoxidil due to adverse events. Overall, oral minoxidil was well tolerated by patients and may benefit both frontal and occipital late alopecia in cancer survivors treated with cytotoxic and/or endocrine therapy by increasing hair shaft and follicle density.

Identification of peripheral blood test parameters predicting the response to palbociclib and endocrine therapy for metastatic breast cancer: a retrospective study in a single institution.

Cyclin-dependent kinase 4/6 inhibitors have been used in endocrine therapy for patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. Although randomized trials have shown that combined therapies prolong progression-free survival (PFS) in comparison to endocrine monotherapy, the predictors of efficacy are unknown. This study aimed to identify the blood test parameters to predict the effects of palbociclib and endocrine therapy. Seventy-nine patients treated with palbociclib and endocrine therapy between December 2017 and June 2022 were reviewed. We assessed PFS in patients according to factors evaluated based on patient characteristics and peripheral blood tests. Patients in the C-reactive protein (CRP)-high, lactate dehydrogenase (LDH)-high, and albumin (Alb)-low groups had significantly shorter PFS than those in the normal group. A multivariate analysis revealed that high LDH and low Alb levels were independent factors that affected PFS. The Alb-low group had an inferior disease control rate. Patients in the CRP-high, LDH-high, and Alb-low groups who received these therapies as first- or second-line treatments showed poor PFS. Several predictors of the efficacy of palbociclib and endocrine therapy were identified in the peripheral blood test parameters of patients with ER-positive and HER2-negative subtypes of metastatic breast cancer.

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.

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.

Abstract PO3-16-10: Real-world outcomes with first-line ribociclib + endocrine therapy in patients with metastatic HR+, HER2– breast cancer: Fourth interim analysis of REACH AUT trial

Abstract Background: Ribociclib (RIB), a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) in combination with endocrine therapy (ET) yielded significant improvement in progression-free survival (PFS) and overall survival (OS) across three phase III MONALEESA trials including patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) metastatic breast cancer (MBC) in first-line (1L) and second-line (2L) setting. In the previous interim analyses of REACH AUT trial, 1L RIB + ET showed tolerable safety and favorable PFS results in a real-world setting. Results from the preplanned fourth interim analysis are reported here. Methods: REACH AUT is a noninterventional study conducted in Austria reporting data on the real-world clinical experience of RIB + ET (aromatase inhibitor [AI] or fulvestrant [FUL]) in premenopausal, perimenopausal, or postmenopausal pts with HR+, HER2– MBC. Pts with no prior ET for advanced disease and maximum up to 1 prior line of chemotherapy (CT) in the advanced setting were included. Results: At data cutoff (March 27, 2023) with a median duration of follow-up of 23.8 months, out of 281 analyzed pts (12.5% of premenopausal/perimenopausal and 85.1% of postmenopausal, 2.5% of unknown status) 31.7% of pts were receiving ongoing treatment. The most common reasons for treatment discontinuations (68.3%) were disease progression (39.1%) and adverse events (AEs, 22.1%). The median age was 63 years (&amp;lt; 65 years, n=156, 55.5%; ≥65 years, n=125, 44.5%) and ECOG PS ≥2: 1.8%. In 106 pts (37.7%), de novo metastatic disease was reported. Visceral metastases (lung, liver) were present in 116 pts (41.3%) and bone-only metastases in 80 pts (28.5%). Prior adjuvant therapy was received by 139 pts (49.5%): AI ± GnRH: n=80 (26.7% without and 1.8% with GnRH); tamoxifen ± GnRH: n=74 (21.7% without and 4.6% with GnRH); CT: n=56 (19.9%); antibody therapy n=3 (1.1%). In the metastatic setting, 1L RIB was prescribed in combination with an AI in 223 pts (79.4%; letrozole: n=139 [49.5%]; anastrozole: n=48 [17.1%]; exemestane: n=47 [16.7%]) and with FUL in 52 pts (18.5%). Prior CT for MBC was received by 5 pts (1.8%). The median PFS was 29.7 months in the overall population; 28.3 months in pts with bone only and 26.9 months in pts with visceral metastatic disease. In pts evaluable for response, the objective response rate and clinical benefit rate were 31.3% and 60.9%, respectively. The OS rates were 91.9%, 81.7%, and 63.7% at 12 months, 24 months, and 36 months, respectively. The trial is ongoing with ~40% of subjects end of documentation and ~27% of deaths. In total, 69.4% of pts had RIB dose interruptions and 48.8% of pts had a RIB dose reduction. The majority of all reported AEs were grade 1 (50.1%) or grade 2 (31.2%); the median time to first AE was 0.5 months. The most common AE was neutropenia (all grades: n=143, 50.9%; grade 1: n=39, 13.9%; grade 2: n=68, 24.2%; grade 3: n=98, 34.9%; grade 4: n=5, 1.8%). QTc prolongation of any grade was observed in 32 pts (11.4%; grade 1: n=24, 8.5%; grade 2: n=11, 3.9%; grade 3: n=1, 0.4%). Hepatobiliary toxicity of any grade was observed in 42 pts (14.9%; grade 1: n=12, 4.3%; grade 2: n=18, 6.4%; grade 3: n=22, 7.8%; grade 4: n=3, 1.1%). Overall, currently 101 pts (35.9%) received a follow-up therapy after progression on RIB + ET. The most common first subsequent therapies were targeted therapies + ET (40.0%), followed by cytotoxic chemotherapy (22.0%) and endocrine monotherapy (19.0%). Conclusion: 1L RIB + ET continues to show favorable efficacy and a tolerable safety profile in the routine clinical practice. The results are consistent with the data from MONALEESA trials. The OS is showing a positive trend but is still immature during this study follow-up. Efficacy Outcomes With RIB + ET in Patients With HR+, HER2– MBC (Overall Population, Nf281) XX XX Citation Format: Christian F. Singer, Daniel Egle, Richard Greil, Edgar Petru, Leopold Oehler, Marija Balic, Laurenz Schöffmann, Georg Pfeiler, Maximilian Marhold, Christine Brunner, Karin Haider, Arik Galid, Ursula Pluschnig, Ferdinand Haslbauer, Michael Hubalek, Andreas Redl, Julia Flatschacher, Shanow Uthman, Bernhard Mraz, Rupert Bartsch. Real-world outcomes with first-line ribociclib + endocrine therapy in patients with metastatic HR+, HER2– breast cancer: Fourth interim analysis of REACH AUT trial [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 PO3-16-10.

Abstract PO2-06-03: Meta-Analysis of Clinical Characteristics and Outcomes in Breast Cancer Patients with Visceral Crisis

Abstract Background: Recent advancements in novel therapeutics have resulted in improved survival over the last decade for patients with metastatic breast cancer, but there remain subsets of patients who experience disproportionately poor outcomes. Patients with visceral crisis (VC), defined by the 5th ESO ESMO as the presence of visceral metastasis with severe organ compromise and/or rapid progression, are often excluded from clinical trials of novel therapeutics. This is despite patients with VC having poorer clinical outcomes and a lack of guidelines consensus on best therapeutic practices. Thus, we sought to better characterize this patient cohort via a meta-analysis to elucidate clinical characteristics and treatment options. Methods: We searched MEDLINE, Embase, Cochrane, Scopus and other sources, from each database's inception to March 2023. The search strategy was designed and conducted by an experienced librarian with input from the study's principal investigator. Controlled vocabulary supplemented with keywords was used to search for patients with breast cancer in visceral crisis. Outcomes of interest included mortality and progression at different time points. Meta-analysis was conducted using the random-effects model. Results: The studies matching our initial inquiry was 154. After evaluation for patient number, and VC related outcomes, 16 studies (12 abstract only) met initial criteria. After data extraction, 12 studies were excluded due to insufficient outcomes delineated by VC. The treatment period was 01/2008 until 01/2022. The mean age at diagnosis of VC was 53.9 with a total of 6404 patients, 6259 were hormone positive, 41 Her2 positive and 87 triple negative. The type of VC included 212 liver dysfunction, 84 respiratory dysfunction, 40 with bone marrow dysfunction, 4 with SVC syndrome, and 43 with meningeal disease (VC type is not reported in every study). The treatments were varied and included multiple platinum doublets, CDK4/6 with endocrine therapy, platinum with bevacizumab, endocrine monotherapy and Her-2 targeted agents. Unfortunately, the number of patients per treatment group or VC type is not enough for targeted outcome analysis. The proportion of patients who progressed at 1, 6, 12 and 18 months were 0.17, 0.64, 0.95 and 0.91 respectively (2 studies Yang et al and Funasaka et al). Mortality assessed as proportion who expired at 1, 6, 12 and 18 months at 0.07, 0.44, 0.64 and 0.77 respectively (3 studies Yang et al, Funasaka et al and Franzoi et al) and at 24 months 0.89 in 4 studies (Yang et al, Funasaka et al, Dawood et al and Franzoi et al) (Table 1). Conclusions In this systematic review, we clearly demonstrate a lack of clinical trial data available to demonstrate specific outcomes based on chemotherapy, visceral crisis type or targeted treatment. The prognosis, however, is consistently poor with mortality at 64 percent by 12 months. Thus, further studies are needed to guide best treatment strategies that address both the poor clinical outcomes and therapeutic toxicities for patients with VC. Clinical trial groups and regulatory bodies overseeing new drug development for breast cancer should consider specific arms for patients with VC, instead of targeted exclusion from trials, as this strategy has proven effective in expansion of therapeutics for other challenging breast cancer subtypes. Table 1 Table 1: Proportion of progression and mortality. Progression studies include Yang et al 2022, Funasaka et al 2021. Mortality studies at 1, 6 and 12 months Yang et al 2022, Funasaka et al 2021 and Franzoi et al 2021. Mortality studies at 24 months Yang et al 2022, Funasaka et al 2021, Franzoi et al 2021, Dawood et al 2021. Citation Format: Michael Auster, Raed Benkhadra, Sophia Lee, Tamarah Aldawoodi, Larry Prokop, Tarek Nayfeh, Paromita Datta, Kate Lathrop. Meta-Analysis of Clinical Characteristics and Outcomes in Breast Cancer Patients with Visceral Crisis [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 PO2-06-03.

Giredestrant for Estrogen Receptor-Positive, HER2-Negative, Previously Treated Advanced Breast Cancer: Results From the Randomized, Phase II acelERA Breast Cancer Study.

To compare giredestrant and physician's choice of endocrine monotherapy (PCET) for estrogen receptor-positive, HER2-negative, advanced breast cancer (BC) in the phase II acelERA BC study (ClinicalTrials.gov identifier: NCT04576455). Post-/pre-/perimenopausal women, or men, age 18 years or older with measurable disease/evaluable bone lesions, whose disease progressed after 1-2 lines of systemic therapy (≤1 targeted, ≤1 chemotherapy regimen, prior fulvestrant allowed) were randomly assigned 1:1 to giredestrant (30 mg oral once daily) or fulvestrant/aromatase inhibitor per local guidelines (+luteinizing hormone-releasing hormone agonist in pre-/perimenopausal women, and men) until disease progression/unacceptable toxicity. Stratification was by visceral versus nonvisceral disease, prior cyclin-dependent kinase 4/6 inhibitor, and prior fulvestrant. The primary end point was investigator-assessed progression-free survival (INV-PFS). At clinical cutoff (February 18, 2022; median follow-up: 7.9 months; N = 303), the INV-PFS hazard ratio (HR) was 0.81 (95% CI, 0.60 to 1.10; P = .1757). In the prespecified secondary end point analysis of INV-PFS by ESR1 mutation (m) status in circulating tumor DNA-evaluable patients (n = 232), the HR in patients with a detectable ESR1m (n = 90) was 0.60 (95% CI, 0.35 to 1.03) versus 0.88 (95% CI, 0.54 to 1.42) in patients with no ESR1m detected (n = 142). Related grade 3-4 adverse events (AEs), serious AEs, and discontinuations due to AEs were balanced across arms. Although the acelERA BC study did not reach statistical significance for its primary INV-PFS end point, there was a consistent treatment effect with giredestrant across most key subgroups and a trend toward favorable benefit among patients with ESR1-mutated tumors. Giredestrant was well tolerated, with a safety profile comparable to PCET and consistent with known endocrine therapy risks. Overall, these data support the continued investigation of giredestrant in other studies.

262 (PB-078) Poster - Efficacy and oncological outcomes of sustained endocrine monotherapy for elderly breast cancer patients

262 (PB-078) Poster - Efficacy and oncological outcomes of sustained endocrine monotherapy for elderly breast cancer patients

A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer

BackgroundHormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 −) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis.MethodsRCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3–5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics.ResultsA total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings.ConclusionsCDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results’ uncertainty, further trials comparing these novel treatments are warranted.Trial registrationRegistration number: PROSPERO (CRD42022377431).

What are the needs in oral antitumor therapy? An analysis of patients' and practitioners' preferences.

Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources. A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options. All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time. Patients and practitioners prefer oral antitumor therapy-both continuous and 21/7 regimens-over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer.

409P Treatment of elderly patients (pts; > 75 years) with 1st-line ribociclib (RIB) + endocrine therapy (ET) or endocrine monotherapy in clinical routine: Real-world data from the RIBANNA study (5th interim analysis (IA))

409P Treatment of elderly patients (pts; > 75 years) with 1st-line ribociclib (RIB) + endocrine therapy (ET) or endocrine monotherapy in clinical routine: Real-world data from the RIBANNA study (5th interim analysis (IA))

Outcomes in Premenopausal Patients with HR+/HER2- Breast Cancer and Lymph Node Micrometastasis Based on the 21-Gene Recurrence Score.

Postmenopausal patients with hormone receptor positive, HER2-negative (HR+/HER2-) early breast cancer (EBC) and 21-gene OncotypeDX (ODX) recurrence scores (RS) <26 do not benefit from chemoendocrine therapy ("CET") compared to endocrine monotherapy ("E"), regardless of nodal status. In premenopausal patients, nodal status is significant in interpretation of RS. However, guidelines are not explicit in recommendations for patients with micrometastasis ("pN1mi" staging). A cohort of patients aged <50 years with HR+/HER2- EBC who underwent ODX testing was identified within the National Cancer Database 2004-2019 dataset. We confirmed the prognostic value of ODX in pN1mi disease with multivariate Cox regression for overall survival (OS). We explored how patterns of practice differed by nodal status in cases of low RS (<26) with chi-squared testing. Finally, we performed Kaplan-Meier models comparing OS for those with RS <26 receiving E versus CET, controlling for nodal status. Of 72 068 patients aged <50 years with HR+/HER2- EBC, 6.1% (n = 4402) had micrometastasis. Multivariate Cox regression confirmed prognostic value of ODX in this pN1mi cohort (P < .001). In the context of RS <26, CET was used most commonly in patients with 1-3 involved lymph nodes ("pN1a-c" disease), less frequently in pN1mi disease, and least in node-negative ("pN0") disease. A benefit in OS was observed in cases with RS <26 and pN1a-c receiving CET vs. E (P = .017), but not in pN1mi (P = .49) or pN0 (P = .57) disease. Our large registry analysis found CET was associated with improved OS in pN1a-c, but not in pN1mi or pN0 disease.

The difference in efficacy of the endocrine therapy between the HER2-low and HER2-zero metastatic breast cancer: A single-center retrospective study.

3 Background: HER2-low expression breast cancer is a new classification and began to receive attention after trastuzumab deruxtecan showed its effect on this classification. As for endocrine therapies, HER2-low expression seemed not to affect the efficacy of CDK4/6 inhibitors in a few retrospective studies. However, previous data on the effectiveness of endocrine therapies other than CDK4/6 inhibitors for HER2-low metastatic breast cancer (mBC) are still limited. This study aims to evaluate the difference in endocrine therapy between HER2-low and HER2-zero mBC. Methods: We retrospectively reviewed the clinical data of mBC patients prescribed aromatase inhibitors, tamoxifen or fulvestrant, and/or CDK4/6 inhibitors at our department between May 2012 and December 2022. Patients were excluded if they received chemotherapy before endocrine therapy, lacked data on HER2 score, or discontinued treatment before the first image evaluation. The data cutoff date was 15th March 2023. We analyzed the difference in progression-free survival (PFS) of the first-line endocrine monotherapy and the first-line CDK4/6 inhibitors between HER2-low and HER2-zero mBC by logrank analysis. Results: Of 126 patients who received the first-line endocrine monotherapy, 22 were HER2-zero, and 104 were HER2-low. In the HER2-zero group, six patients received tamoxifen, and 16 received AIs. In the HER2-low group, 29 patients received tamoxifen, 63 received AIs, and 12 received fulvestrant. The median PFS was 27.7 months with the HER2-zero group and 15.6 months with the HER2-low group. This was not statistically significant (P=0.196), but the Kaplan-Meier curve showed that PFS tended to be longer with the HER2-zero group. This trend was also observed in patients who received AIs. Of 52 patients who received CDK4/6 inhibitors as a first-line treatment, ten were HER2-zero, and 42 were HER2-low. The median PFS was NA with the HER2-zero group and 22.8 months with the HER2-low group, and no significant differences were detected. Conclusions: In this study, there were no statistically significant differences in the PFS of the first-line endocrine monotherapy and CDK4/6 inhibitors between HER2-low and HER2-zero mBC. However, the Kaplan-Meier curve showed that the PFS of endocrine therapy tended to be longer in the HER2-zero group. Further studies are warranted.

Real World Experience of Second-Line Treatment Strategies after Palbociclib and Letrozole: Overall Survival in Metastatic Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer

Background: We analyzed real-world practice of second-line treatment in hormone receptor (HR)+ human epidermal growth factor receptor-2 (HER2)− metastatic breast cancer (MBC) following the first-line CDK4/6 inhibitor with letrozole. In addition, we evaluated the relationship between second-line treatment strategies and survival outcome. Methods: Using the clinical data warehouse, clinical information including MBC diagnosis, treatment and survival outcomes were collected. Results: In total, 305 patients were treated with the first-line palbociclib plus letrozole, and we evaluated 166 patients who were treated with second-line treatment. Of the 166 patients, 28.5% were treated with capecitabine (C), followed by exemestane with everolimus (EE) (27.3%) or cytotoxic chemotherapy other than capecitabine (T) (18.8%) and fulvestrant-based treatment or endocrine monotherapy (F) (12.7%). Eighteen patients (10.9%) were enrolled in clinical trials (CT). With regard to treatment strategies, and the median progression-free survival of second-line treatment in a metastatic setting (PFS2) was 7.4 months with C, 5.2 months with EE, 4.8 months with T, 3.6 months with F, and 3.6 months with CT (p = 0.066). In patients with visceral organ disease progression, C (31.3%) or T(31.3%) was the most common second-line treatment followed by EE (21.9%). Most of the 47 patients with bone metastasis alone were treated with EE (38.2%), followed by C (23.4%) and F (21.3%) (p = 0.008). The median overall survival of second-line treatment in a metastatic setting (OS2) was 42.3 months with C, 35.7 months with F, 30.7 months with EE, and 23.1 months with T. The median OS2 for those in CT was not reached (p = 0.064). ER driven BC, disease progression site and PFS2 were associated with OS and OS2 in HR+HER2− MBC (ps &lt; 0.05). Conclusions: We suggested the second line treatment strategy was important to improve prognosis in patients with HR+/HER2− MBC, especially given the recent standardization of first-line treatment and the many available second-line options.

Primary outcome analysis of the phase 3 SONIA trial (BOOG 2017-03) on selecting the optimal position of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC).

LBA1000 Background: The phase-3, randomized, investigator-initiated, nationwide SONIA trial is evaluating the efficacy, safety and cost-effectiveness of CDK4/6i added to either first- or second-line endocrine therapy (ET) in patients with HR+, HER2- ABC who have received no prior therapy for ABC. The addition of CDK4/6i to ET improves progression-free (PFS) and overall survival (OS) in HR+, HER2- ABC, as initial treatment (first-line) and after prior endocrine monotherapy (second-line). Most international guidelines advice first-line use, despite prolonged toxicity and a steep increase in costs compared to use in second-line. Evidence of superiority of first-line use over second-line based on a head-to-head comparison is lacking. Methods: Pre- and postmenopausal women (N=1050), who received no prior therapy for ABC, with measurable or evaluable disease and WHO performance status 0-2 were enrolled in 74 Dutch hospitals. (Neo)adjuvant therapy was allowed (disease-free interval after non-steroidal aromatase inhibitor (NSAI) &gt;12 months). Patients were randomized 1:1 to receive strategy A (first-line treatment with an NSAI + CDK4/6i, followed on progression by fulvestrant (F)) or strategy B (first-line treatment with an NSAI, followed on progression by F + CDK4/6i). Choice between one of the available CDK4/6i (abemaciclib, palbociclib, ribociclib) was a stratification factor and left to the discretion of the treating physician. The primary endpoint is time from randomization to second objective disease progression, as assessed by local investigators, or death (PFS2). Secondary endpoints include OS, safety, quality of life, and cost-effectiveness. Results: After a median follow-up of 37.3 months (data cut-off 1 December 2022), median PFS2 was 31.0 months in strategy A versus 26.8 months in strategy B (hazard ratio 0.87; 95% confidence interval, 0.74 to 1.03; P=0.10). The treatment effect was consistent across the levels of pre-defined subgroups. The safety profile was characteristic for ET + CDK4/6i. Median time on CDK4/6i was 24.64 months in strategy A and 8.08 months in strategy B (Δ 16.56 months). The number of grade ≥3 adverse events was 2782 for strategy A and 1620 for strategy B. Conclusions: First-line use of CDK4/6i + ET does not provide statistically significant, nor clinically meaningful PFS benefit compared to second-line use in women with HR+, HER2- ABC. Use in first-line prolongs the time on CDK4/6i by 16.56 months and increases toxicity and costs. Second-line use may thus be a preferred option for the majority of patients. (Funded by The Netherlands Organisation for Health Research and Development and Dutch Health Insurers; ClinicalTrials.gov number, NCT03425838). Clinical trial information: NCT03425838 .

Adjuvant hormone therapy in early-stage estrogen-positive breast cancer: a systematic review and network meta-analysis

Relevance. Adjuvant hormonal therapy in postmenopausal women at an early-stage of estrogen-positive breast cancer (BC) includes anastrozole, letrozole, tamoxifen, toremifene, and exemestane, but the most effective drug is not known, and in this situation, the role of adjuvant hormonal therapy becomes especially debatable.The purpose of the study. Conducting an indirect comparison of oestrogen antagonists and aromatase inhibitors used in postmenopausal women with early-stage estrogen-positive breast cancer through a systematic search and selection of transitive data from randomized controlled trials (RCTs), and their subsequent quantitative synthesis in a network meta-analysis.Methods. We conducted a systematic review in two databases: MEDLINE and The Cochrane Central Register of Controlled Trials. Full-text versions of articles from RCTs were reviewed to evaluate the comparative efficacy of adjuvant hormonal monotherapy with toremifene, tamoxifen, anastrozole, letrozole, and exemestane in women with early-stage estrogen-positive postmenopausal breast cancer who had not previously received hormone therapy. Efficacy was assessed by overall survival (OS). A network meta-analysis was carried out using the NetMetaXL programme.Results. As a result of a systematic search, we selected 8 RCTs involving 25167 patients. When performing a synthesis of the obtained data using a network meta-analysis, no statistically significant differences in 5-year OS were obtained between the comparators.Conclusions. There are no clinically significant differences in 5-year OS between the compared drugs of adjuvant hormonal monotherapy in early-stage breast cancer.

Real-world efficacy of ribociclib (RIB) + aromatase inhibitor (AI)/fulvestrant (FUL), or endocrine monotherapy (ET), or chemotherapy (CT) as first-line (1L) treatment (tx) in elderly patients (pts; &gt; 75 years) with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Results of fifth interim analysis (IA) from RIBANNA.

e13050 Background: RIB+ET has demonstrated a statistically significant survival benefit across three phase 3 MONALEESA trials, irrespective of menopausal status, line of therapy, or combination partner. RIBANNA (CLEE011ADE03), a prospective, noninterventional study assessing the efficacy and safety of RIB+ET, or ET alone or CT in 1L setting in pre-, peri- and postmenopausal women with HR+, HER2– ABC is ongoing in Germany since October 2017. In this 5th IA from RIBANNA, efficacy, safety, and tolerability for exclusively elderly pts ( &gt; 75 years) will be presented. Methods: Pts were included in accordance with the German tx guideline. The following analysis will be performed exclusively for pts &gt; 75 years. Effectiveness analysis for PFS will be performed including propensity score matched (PSM) and Cox Proportional Hazards Regression (CPHR) analysis. Data for patient-reported outcomes (PRO) were collected at baseline and every 3 months until the end of treatment and will be evaluated using the Morisky Medication Adherence Scale (MMAS-8), questionnaires related to quality-of-life (EORTC QLQ-C30) and its breast cancer–specific module (EORTC QLQ-BR23) as well as the Hospital Anxiety and Depression Scale (HADS). Results: At data cutoff Sep 6, 2022, 2581 pts were enrolled in the study (RIB+AI/FUL, n = 2163; ET, n = 237; CT, n = 181). For pts &gt; 75 years data from n = 434 (RIB+AI/FUL), n = 83 (ET) and n = 20 (CT) are available. In the overall population at baseline, the mean age (standard deviation [SD]) of patients was 65.5 (11.6), 70.8 (11.3), and 61.8 (11.6) years in the RIB + AI/FUL, ET, and CT cohorts, respectively. The unadjusted KM estimate for median PFS was 32.2 months (95% CI, 29.3–34.8) in the RIB + AI/FUL cohort, 35.2 months (95% CI, 23.9–44.2) in the ET cohort, and 16.7 months (95% CI, 9.9–17.5) in the CT cohort. Multivariate analysis showed that PFS was independently affected by several baseline parameter. After CPHR Analysis RIB + AI/FUL was associated with prolonged PFS compared with ET or CT. These results could be confirmed using PSM. The most frequent treatment-emergent adverse events (AEs) (all grade) in the RIB + AI/FUL cohort were neutropenia (25.8%), nausea (25.1%), fatigue (24.2%), and leukopenia (19.8%). Nausea and fatigue were the most common treatment-emergent AE (all grade) in both the CT and ET cohorts. Conclusions: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. In the overall population Ribociclib showed superiority over ET and CT in the clinical routine, without new safety signals. Data for exclusively elderly pts ( &gt; 75 years) will be presented.

Outcome of second-line treatment after CDK4/6 inhibitors in hormonal-positive HER-2 negative metastatic breast cancer: Single institution experience.

e13053 Background: In patients with metastatic hormonal receptors (HR)-positive, HER2-negative breast cancer, CDK 4/6 inhibitors with hormonal therapy is the current standard first line therapy in patients without visceral crisis. Limited data is available about the outcome of second line therapy after CDK 4/6 inhibitors. In this study, we reported the survival outcome of second line systemic therapy after CDK 4/6 inhibitors in a single institute in Saudi Arabia. Methods: We retrospectively checked patients with metastatic HR-positive, HER2-negative breast cancer who received first line therapy with palbociclib in addition to an aromatase inhibitor in King Abdullah Medical City, Saudi Arabia. Patients who received second line systemic therapy were recruited. Different clinicopathological data were checked in addition to type of second line therapy, dates of starting 1st and second lines therapy and dates of progression. We check progression-free survival (PFS) with second line therapy in relation to the type of second line therapy, duration of 1st line therapy and other potential prognostic factors. Results: We recruited 59 eligible patients. Median PFS of the study group was 4 months (95% CI 2.9-5.1). No significant difference in PFS according to type of second line systemic therapy (chemotherapy: 4 months, everolimus with hormonal therapy: 6 months, hormonal monotherapy: 3 months, p=0.17). In addition, there was no significance difference in second line therapy PFS according to duration of 1st line palbociclib-hormonal therapy (≤ 12 months: 4 months vs. &gt;12 months: 5 months, HR 0.97, 95% CI: 0.55-1.7, p=0.92). Similarly, taking 6 months as a cutoff, no significant difference in PFS (≤ 6 months: 4 months, &gt;6 months: 6 months, HR 0.73, 95% CI: 0.43-1.24, p=0.25). Similarly, no difference in second line PFS according to menopausal status, age at diagnosis (≤ 50 vs &gt;50) or ER-Allred score (≤ 6 vs &gt;6). Conclusions: Outcome of 2nd line systemic therapy following first line palbociclib with hormonal therapy was poor in the study cohort. No significant difference in PFS according to type of systemic therapy, duration of first line therapy, or other clinicopathological factors.