First-line Treatment Of Metastatic Breast Cancer Research Articles

Abstract PO4-10-04: Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative breast cancer

Abstract Introduction: Black and younger patients are more likely to have aggressive forms of breast cancer. Endocrine therapy (ET) plus a CDK4/6 inhibitor is the standard of care first-line therapy for patients with hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (MBC). Recent data has shown better outcomes with this approach compared to chemotherapy, even for patients with aggressive disease. Our study looked at differences in first-line treatment among Black and younger women with HR+/HER2- MBC. Methods: Clinical characteristics, treatment, and outcomes of patients diagnosed with HR+/HER2- MBC between 2011-2022 were retrieved from the UNC Metastatic Breast Cancer Database. Log binomial regression modeling compared treatment choices by group, and Cox proportional hazards regression modeling evaluated progression-free survival (PFS) from the start of treatment. Results: 524 patients were included in this analysis. 30% were young patients (< 50 years of age), 20% were Black patients, 62% had only 1 site of metastasis and 51% had visceral involvement. When looking at first-line treatment for metastatic disease, 21% of overall patients had received chemotherapy. The likelihood of receiving chemotherapy was higher for younger verses (vs) older patients (29% vs 18%, RR=1.63, p=0.004), for Black vs White patients (31% vs 18%, RR=1.71, p=0.002), and for those with visceral vs non-visceral involvement (26% vs 16%, RR=1.67, p=0.004). A model including age, race, and visceral involvement showed similar findings. Among patients who received ET as the first line treatment for metastatic disease, the likelihood of receiving CDK 4/6 inhibitors in addition to ET was lower for young Black patients compared to young White patients (41% vs 74%, RR=0.55, p=0.02). However, among older patients >=50, no significant difference was seen by race (Blacks 60% vs Whites 56%, RR=1.1, p=0.61). Adjusting for visceral involvement showed similar findings. Patients who received ET (with or without CDK 4/6 inhibitors) had better PFS compared to patients receiving chemotherapy as first-line therapy (HR 0.65, 95% CI 0.49, 0.88, p=0.005), this held true after adjusting for age, race, treatment group and visceral involvement (HR 0.7, p=0.02). A stratified analysis showed similar findings within Black patients (HR 0.42, p=0.003), and young patients (HR 0.55, p=0.01). Conclusion: Overall, Black and younger patients were more likely to receive chemotherapy as the first-line treatment for metastatic disease. Among patients who received ET as the first-line treatment for MBC, young Black patients were less likely to receive CDK 4/6 inhibitors compared to young White patients. Further studies are needed to outline the multi-level factors contributing to the identified disparities in care among patients with HR+/HER2- MBC. Citation Format: Yara Abdou, Joannie Ivory, Allison Deal, Ally Wardell, Amy Wheless, Claire Dees, Lisa Carey. Treatment differences by race and age in metastatic hormone receptor-positive/HER2-negative 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 PO4-10-04.

Abstract PO3-05-02: Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort

Abstract Background: In patients (pts) with early breast cancer (BC), the level of expression of estrogen receptor (ER) evaluated by immunohistochemistry is prognostic and predictive while progesterone receptor (PR) expression has an additional prognostic value. Allred scoring combines the percentage of positive cells and the intensity of staining. It is widely used for treatment choice for early BC. In metastatic setting, its role is less defined. Methods: The ESME database is a French National cohort of all consecutive pts who initiated a first-line treatment for metastatic BC (MBC) between January 2008 and December 2020 in one of the 18 French Comprehensive Cancer Centers (NCT03275311). For this study, we selected pts with HER2- MBC, known ER expression and intensity percentages, known PR status and who received endocrine-based therapy as first-line metastatic treatment. Primary objective was to evaluate the overall survival (OS) and first line progression-free survival (PFS1) under endocrine therapy according to ER and PR expression level. ER expression was defined using Allred score on the last available tumor sample. PR status was defined using a positive (≥10%)vs negative ( < 10%) threshold. Secondary objective was to evaluate clinical PFS1 whether de novo or recurrent MBC and according to type of first line therapy (mono- vs combined endocrine therapy). Results: In the ER+ ± PR+/HER2- population, 8269 pts had information on ER percentage and staining intensity. Median follow-up was 53.4 months (95%CI [51.9; 54.7]). Allred score distribution, OS and PFS1 are described in table 1. Median OS was 43.1 months [41.1; 45.0] for the PR- group compared with 52.3 months [50.5; 54.4] for the PR+ group. After adjustments, patients with a PR- tumour had still a worse prognosis (HR=1.20, 95%CI [1.12-1.28], p<0.001). Median PFS1 was 10.2 months[9.6; 10.8]and 14.8 months[14.2; 15.4] for pts with PR- vs PR+ tumour (HR=1.36 (1.29-1.43), p<0.001) and PR status remained significant prognostic factor independently of de novo or recurrent status and association or not with a targeted therapy. Conclusion: ER expression evaluated using the Allred scoring, as well as PR positivity, retain prognostic value in first-line MBC patients. Table 1 : OS and PFS according to Allred status, de novo status and type of endocrine therapy. * Selected variables on multivariate model include PR status, age, SBR grade, histological subtype, number of metastatic site, type of metastasis (non visceral, visceral, brain visceral), HER 2 (0 vs 1-2), metastatic-free interval, mono- vs combined endocrine therapy. Citation Format: Marie Alexandre, Florence Castan, Thibault De La Motte Rouge, Audrey Mailliez, Etienne Brain, Thomas Bachelot, Monica Arnedos, Florence Dalenc, Jean-Marc Ferrero, Vincent Massard, Isabelle Desmoulins, Marie-Ange Mouret-Reynier, Christelle Levy, Anthony Gonçalves, Anca Berghian, Aude-marie Savoye, Jean-Sébastien frenel, Lise Bosquet, Suzette Delaloge, William Jacot. Impact of hormone receptor expression level in HR+/HER2- metastatic breast cancer in the large French ESME cohort [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 PO3-05-02.

Abstract PO4-04-14: Change of first-line treatment pattern in metastatic luminal breast cancer: Results from the Austrian AGMT_MBC-Registry

Abstract Background: For patients with HR+/HER2- (luminal) metastatic breast cancer (MBC), international guidelines recommend endocrine-based first-line therapy [ET] in combination with a CDK4/6 inhibitor for most patients. Only for patients with imminent organ failure, first-line chemotherapy should be considered. To clarify changing patterns of first-line treatments over time in an Austrian population of luminal MBC patients, we analyzed the data from the MBC registry of the Austrian Study Group for Medical Tumor Therapy (AGMT-MBC-Registry). Methods: The AGMT-MBC-Registry is an ongoing multicenter registry for MBC patients in Austria. Only patients with luminal MBC and sufficient outcome data were included in this analysis. Patients were assigned to one of the following groups according to the year of start of first-line treatment for MBC: 2001-2010, 2011-2013 (no CDK4/6i available for first-line in both periods), 2014-2016 (CDK4/6i available in early access programs and clinical trials for first-line only), 2017-2019, and 2020-2022 (CDK4/6i available in both periods). Time to first chemotherapy (TTC) defined as start of first-line treatment until first application of a cytotoxic agent, and overall survival (OS) defined as start of first-line treatment until death were calculated by the Kaplan-Meier method and compared using the log-rank test. OS analysis was adjusted for disease free survival (DFS) category (de novo, DFS < 24 month, DFS ≥ 24 month), menopausal status (pre-, postmenopausal, unknown), age at diagnosis of metastatic disease (continuous), number of metastatic sites at diagnosis (1, 2-3, > 3), visceral disease (no, yes), and Charlson comorbidity index at diagnosis (continuous). Results: As of May 16th 2023, 1,330 patients with HR+/HER2- disease receiving at least one treatment-line for MBC were evaluable. First-line treatments significantly changed over time (P < 0.001). In patients diagnosed between 2001 and 2010, 61.4% were treated with first-line chemotherapy compared to 10.0% in patients diagnosed between 2020 and 2022 (Table 1). Additionally, TTC also significantly increased over time (P < 0.001; Table 2). In contrast, the proportion of patients treated with a first-line CDK4/6i plus endocrine therapy combination increased over time from 4.4% in 2014-2016 up to 75.5% in the period of 2020-2022. Additionally, adjusted median overall survival estimates significantly increased over time (P < 0.001; Table 2). Conclusion: In our registry, the proportion of patients with luminal MBC treated with first-line chemotherapy significantly decreased over time, whereas the proportion or patients treated with first-line CDK4-6 inhibitors significantly increased. This is in line with the change of guideline recommendation as well as the availability of CDK4-6 inhibitors over the last 2 decades. The availability of new treatment options has significantly increased median overall survival over time. Table 1: First-line treatment pattern over time Period N ET ET plus CDK4/6i Chemotherapy Others* 2001-2010 220 84 (38.2%) 0 (0.0%) 135 (61.4%) 1 (0.5%) 2011-2013 238 116 (48.7%) 0 (0.0%) 110 (46.2%) 12 (5.0%) 2014-2016 318 174 (54.7%) 14 (4.4%) 99 (31.1%) 31 (9.7%) 2017-2019 293 60 (20.5%) 190 (64.8%) 36 (12.3%) 7 (2.4%) 2020-2022 249 22 (8.8%) 188 (75.5%) 25 (10.0%) 14 (5.6%) Overall 1,318 456 (34.6%) 392 (29.7%) 405 (30.7%) 65 (4.9%) Legend: N - number of patients, ET - endocrine therapy (tamoxifen, aromatase inhibitor and/or fulvestrant), CDK4/6i - CDK4/6 inhibitor; * e.g. endocrine treatment plus everolimus or investigational study treatment Table 2: Time to first chemotherapy (TCC) and overall survial (OS) over time Period Median TTC [months] Adjusted median OS [months] 2001-2010 0.0 (0.0 - 0.0) 49.4 (41.2 - 56.6) 2011-2013 4.3 (0.0 - 13.8) 48.2 (38.3 – 69.7) 2014-2016 20.0 (14.0 - 26.4) 60.3 (50.2 - 77.5) 2017-2019 40.1 (33.3 - 59.8) 60.8 (52.8 - NR) 2020-now 30.4 (27.6 - NR) NR (NR - NR) Legend: N - number of patients, NR - not reached Citation Format: Gabriel Rinnerthaler, Simon Gampenrieder, Angelika Pichler, Walter Herz, Andreas Petzer, Renate Pusch, Marija Balic, Christoph Suppan, Sonja Heibl, Lukas Scagnetti, Margit Sandholzer, Clemens Schmitt, August Zabernigg, Daniel Egle, Petra Pichler, Christopher Hager, Florian Roitner, Johannes Andel, Kathrin Strasser-Weippl, Rupert Bartsch, Michael Hubalek, Michael Knauer, Christian F. Singer, Richard Greil. Change of first-line treatment pattern in metastatic luminal breast cancer: Results from the Austrian AGMT_MBC-Registry [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 PO4-04-14.

Abstract PO2-16-10: Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia

Abstract Background: Traditionally, breast cancer subtyping has described patients as HER2-negative or HER2-positive, with the latter being those in whom HER2-directed therapies are utilised. A proportion of HER2-negative cancers can be classified as “HER2-low” as they express IHC 1+ or 2+ and are non-amplified on in-situ hybridisation (ISH). Until recently, our widely available HER2-targeted therapies have proven to be ineffective in this subtype. The DESTINY-BREAST04 trial (Modi et al, NEJM 2022) showed progression-free and overall survival efficacy of HER2-directed therapy using the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) in HER2-low disease, suggesting a need to identify this population for selected therapy. This study evaluated a real-world population of metastatic breast cancer (MBC) patients treated according to traditional breast cancer subtypes to determine the frequency of HER2-low histology, with a focus on selection of first-line therapy. Methods: This retrospective audit identified patients being treated for MBC at a single tertiary hospital (Austin Health in Melbourne, Australia) over a 3.5 year period. Patients were identified from an electronic database, with a date of last follow-up as August 2022. Medical records were interrogated for clinicopathological information including review of pathology reports for breast cancer subtypes. Traditional breast cancer subtypes were defined as (i) ER positive and HER2-negative (HER2 0 or 1+, or 2+ and non-amplified); (ii) HER2-positive (HER2 3+ and/or amplified) and (iii) TNBC (negative for ER and PgR, and HER2 0 or 1+, or 2+ and non-amplified). Selection and duration of first-line treatment for MBC was also recorded. Results: Between March 2018 and August 2022, 202 MBC patients were identified. Based on traditional subtypes, 126 (62%) were ER positive and HER2-negative, 46 (23%) were HER2-positive, 26 (13%) were TNBC and 4 (2%) were unknown. In the total population, 87 (43%) were classified as having HER2-low disease based on retrospective pathology reports. HER2-low represented 61% of ER positive, HER2-non amplified patients and 45% of TNBC patients. Metastatic specimen data was known for 172 cases and of these, 95 patients (55%) were re-biopsied on metastatic progression. This occurred more commonly with HER2-positive (81%) and ER positive HER2-negative (78%) primaries. The most common change in subtype was loss of ER, which occurred in 7 patients (3%). Changes in HER2 status occurred in 29 (14%) of patients, most commonly as either an increase from 1+ to 2+ or decrease from 1+ to 0. HER2-low status remained consistent for 67% of patients who underwent biopsy on recurrence. For patients with ER positive HER2-negative MBC, first-line combination therapy with a CDK4/6 inhibitor + AI was preferred (51%), followed by single agent endocrine therapy (30%) and chemotherapy (17%). The majority (84%) of HER2-positive patients received first-line dual HER2 therapy (trastuzumab and pertuzumab) with taxane chemotherapy. Half of TNBC patients received upfront chemotherapy, with physician preference being capecitabine (45%). There was no significant difference in PFS between the HER2-low vs. HER2-0 cohorts, for either ER positive or TNBC subtypes. No patients in this series were treated based on HER2-low definition due to no funded access to such therapies at the time. Conclusion: HER2-low has emerged as an identifier for patients who may respond to HER2-directed therapies using ADCs such as T-DXd. However, its clinical significance as a discrete clinical subtype remains uncertain. In this retrospective audit, HER2-low patients were identified in both ER positive and TNBC subtypes. Dynamic changes in HER2 staining occurred infrequently. Further evaluation is needed to address whether HER2-low expression provides any prognostic value and whether prospective reporting of HER2-low status may alter how these new HER2-directed therapies are used in future. Citation Format: Michelle Li, Belinda Yeo. Characterising HER2-low status in metastatic breast cancer: a real-world retrospective study of patients at a metropolitan cancer centre in Australia [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 PO2-16-10.

Cost-utility analysis of Palbociclib + letrozole and ribociclib + letrozole versus Letrozole monotherapy in the first-line treatment of metastatic breast cancer in Iran using partitioned survival model

BackgroundPalbociclib and Ribociclib are cyclin-dependent kinase 4/6 oral molecular inhibitors that have the potential to improve overall survival (OS), progression-free survival (PFS), and quality of life in patients with metastatic breast cancer (MBC). The objective of this study was to analyze the cost-utility of Palbociclib and Ribociclib in comparison with Letrozole monotherapy as the first-line treatment for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2–) MBC patients in Iran.MethodsA Cost-Utility Analysis (CUA) was conducted using a partitioned survival model (PSM) from the perspective of the Iranian healthcare system. The comparative strategies considered were Palbociclib + Letrozole, Ribociclib + Letrozole, and Letrozole monotherapy. The model was structured with a 1-month cycle length and a 15-year time horizon. Clinical safety, efficacy, and survival data in terms of PFS and OS for Palbociclib + Letrozole and Ribociclib + Letrozole were obtained from the latest updates of the PALOMA-1, 2, and MONALEESA-2 studies, respectively. Direct medical costs, including drug costs, visits, hospitalization, CT scans, bone x-rays, monitoring and laboratory testing, as well as medication side effects, were considered. Uncertainty evaluations were performed through deterministic sensitivity analysis and probabilistic sensitivity analysis. Excel 2016 and TreeAge 2020 were used for all stages of the evaluation.ResultsThe base case results indicated that, despite its lower effectiveness, Letrozole monotherapy was the most cost-effective strategy, while Palbociclib + Letrozole and Ribociclib + Letrozole were not cost-effective. The incremental cost-effectiveness ratios (ICERs) for Palbociclib + Letrozole and Ribociclib + Letrozole compared to Letrozole monotherapy were estimated at $137,302 and $120,478 per quality-adjusted life-year (QALY), respectively, which exceeded the target threshold of $4565. Deterministic sensitivity analysis demonstrated that the CUA results were not sensitive to changes in the values of uncertain variables. Probabilistic sensitivity analysis also indicated that Palbociclib + Letrozole and Ribociclib + Letrozole had no chance of being cost-effective based on changes in various parameters and simulations.ConclusionsPalbociclib and Ribociclib showed significant efficacy in combination with Letrozole, as evidenced by improvements in PFS. However, in the first-line treatment of MBC in Iran, these strategies were not cost-effective compared to Letrozole monotherapy.

Non-pegylated liposomal doxorubicin plus cyclophosphamide as first-line therapy in elderly women with HER2 negative metastatic breast cancer.

The use of anthracyclines in metastatic breast cancer (MBC) is limited by cumulative dose-dependent cardiotoxicity mostly in elderly women with comorbidities. The aim of this observational retrospective study was to evaluate the efficacy of non-pegylated liposomal doxorubicin (Myocet®) and cyclophosphamide in elderly women as HER2 negative first-line MBC treatment. 84 elderly women >70 years of age (median age 78 years) with MBC HER2 negative were enrolled. Performance Status in 58 patients was ECOG-0 and in 26 patients was ECOG-1. The drug was well tolerated, with overall response rates were >40%, median overall survival was 16.2 months (95%CI:14.6-18.8) and median progression free survival was 5.8 months (95%CI:4.4-8.6). Hematologic toxicity with neutropenia was the most frequent adverse event, but the treatment was well tolerated maintained a manageable cardiotoxicity. Non-pegylated liposomal doxorubicin may represent a valid therapeutic option in first-line for elderly patients with HER/2 negative MBC improving survival, anti-tumor response rate and de-creases cardiotoxicity.

The prolonged clinical benefit with metronomic chemotherapy (VEX regimen) in metastatic breast cancer patients.

Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.

Predictors of non-receipt of first-line CDK 4/6 inhibitors (CDK4/6i) among patients with metastatic breast cancer (MBC).

1016 Background: CDK4/6i improve survival outcomes for first-line treatment of patients with hormone receptor positive (HR+), human epidermal growth factor-2 negative (HER2-) MBC. Yet, not all eligible patients (pts) receive a first-line CDK4/6i. We sought to describe factors associated with not receiving a first-line CDK 4/6i among MBC pts treated at our institution. Methods: Retrospective cohort of pts with HR+, HER2- MBC diagnosed between May 1, 2015 and June 30, 2019 treated at Johns Hopkins clinic sites in Baltimore City (BCi), Baltimore County (BCo), and Washington DC (DC). Primary outcome was receipt of a first-line CDK 4/6i. Clinical and demographic factors were abstracted from the electronic medical record. Patient zip-code was used to define a low-income neighborhood (LIN) as an area where >10% of households have median income below the federal poverty level. Univariate and multivariable logistic regression models (determined using a stepwise model selection approach) were performed to identify factors associated with not receiving a first-line CDK 4/6i. Results: Of the 211 pts in the cohort, 203 (96.2%) were female, 133 (63%) were White, and 53 (25%) were Black. Median age was 58 yrs (range 25-90 yrs). 26% of pts had de novo MBC and 44% had visceral disease at diagnosis. About half, 104 (49%), were privately insured, 83 (49%) had Medicare, and 15 (7.1%) had managed care plans including Medicaid. 118 (56%), 43 (20%), and 50 (24%) pts were treated in BCi, BCo, and DC respectively. 60% (n=126) of pts received a first-line CDK 4/6i and there was a trend of increased utilization over time with 39% of pts receiving first-line CDK4/6i in 2015 and 67% in 2019. On univariate analysis, LIN, clinic site, and year of MBC diagnosis (2015-2017 vs 2018-2019) were associated with first-line CDK4/6i use. The multivariable model included age, race, clinic site, LIN, and year of MBC diagnosis. In this model, pts treated in BCi were 58% less likely to receive first-line CDK 4/6i compared to those treated in BCo (OR 0.42, 95% CI 0.18-0.95). Those diagnosed with MBC in 2017 or later were 2.6 times more likely to receive first-line CDK4/6i than those diagnosed prior (OR 2.63, 95% CI 1.45-4.83). Those who lived in a LIN were 39% less likely to receive first-line CDK4/6i vs those in a non-LIN, though this was no longer statistically significant (OR 0.61, 95% CI 0.32-1.13). Conclusions: We identified disparities in the use of CDK4/6i for first-line treatment of MBC. Lower use was observed among pts who received care at our urban Baltimore city site with a trend towards lower use among pts from lower-income neighborhoods. These findings highlight potential barriers with accessing oral cancer therapies - cost, patient distrust, and/or systemic bias. Further work is needed to delineate the multi-level factors contributing to these disparities and to develop resources to overcome these barriers and achieve equitable utilization of these drugs.

Abstract PD10-11: Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database

Abstract Background: Platinum-based chemotherapy regimens (PtCT) have been shown to increase treatment efficacy when combined to neoadjuvant standard of care treatment of triple negative breast cancers (TNBC). In the metastatic breast cancer (MBC) setting, preclinical and clinical data suggest that PtCT could be more efficient than non-platinum based ones (non-PtCT) among patients (pts) with germline BRCA1/2 mutations (gBRCAm). However, published data remain controversial on this topic, particularly for MBC. We evaluated the progression-free (PFS) and overall survival (OS) under first-line PtCT and non-PtCT among gBRCAm carriers in ESME, a nationwide real-life MBC database. Methods: ESME MBC database (NCT03275311), is a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. Women with HER2- MBC and known hormone receptors (HR) and gBRCA1/2 (before or in the 6 first months of metastatic disease, gBRCAm / wild type / not tested) status, who received a first-line MBC CT were selected. Patients with other germinal mutations were considered as wild type. Primary objectives were OS and PFS under first-line CT (PtCT vs. non-PtCT) in the TNBC gBRCA1/2m population.Secondary objectives were OS and PFS during first-line CT (PtCT vs. non-PtCT) in the TNBC wild-type and “not tested” population, as well as among the HR+/HER2- pts.To avoid guarantee time bias related to oncogenetic testing, analyses were performed at baseline (CT initiation) and different landmark time points (3-month or 6-month after CT initiation). Thus, BRCA status was defined according to oncogenetic testings performed before the landmark time, and patients who progressed or censored before the landmark time were excluded. Results: 10,164 pts (2,794 TNBC; 7,370 HR+/HER2-) were included in this analysis. Pts who received PtCT were significantly younger, affected by a gBRCA1/2m, had a high histological grade and/or TNBC tumor, with more frequent visceral and central nervous system spreading than non PtCT ones. Median follow-up was 51.1 months [95%CI 49.6; 52.6]. All reported results were based on the gBRCA status defined at CT initiation and on multivariable analysis adjusted on age at MBC diagnosis, de novo MBC status, type and number of metastases. In the gBRCA1/2m TNBC population (N=132), PtCT was independently associated with a better PFS compared to non-PtCT (HR=0.56, 95%CI 0.38-0.84, p=0.005), without significant difference in OS (HR=0.79, 95%CI 0.51-1.23, p=0.29).No difference was seen in wild-type BRCA1/2 TNBC pts (N=269) according to the CT regimen, while, in the larger population of untested TNBC (N=2,393), PtCT was associated with worse OS (HR=1.18, 95%CI 1.03-1.34, p=0.016) compared to non-PtCT regimens, without significant difference in PFS (HR=1.07, 95%CI 0.95-1.22, p=0.26). No significant difference was seen regarding PFS nor OS in gBRCA1/2m HR+/HER2- pts (N=124) and in the wild-type BRCA1/2 HR+/HER2- population.However, in the larger population of untested HR+/HER2- pts (N=6,836), PtCT was independently associated with worse OS (HR=2.15, 95%CI 1.79-2.59, p<0.001) and PFS (HR=1.57, 95%CI 1.33-1.86, p<0.001) compared to non-PtCT regimens. Results were similar in landmark analyses at 3-month or 6-month after CT initiation. Conclusions: This large-scale real-life analysis suggests higher efficacy of PtCT in term of PFS in gBRCA1/2m TNBC pts. The small sample size and post-1st line treatments may preclude observing a significant OS difference. PtCT appeared however associated with worse outcomes in untested TNBC and HR+/HER2- pts. These results emphasize the need for BRCA1/2 characterization before considering these regimens in the MBC setting. Citation Format: William Jacot, Amélie Lusque, Audrey Mailliez, Thibault De la Motte Rouge, Luc Cabel, Christelle Levy, Anne Patsouris, Isabelle Desmoulins, Lionel Uwer, Marianne Leheurteur, Mathieu Robain, Olivier Caron, Thomas Bachelot, Thomas Filleron, Jean-Sébastien Frenel, Suzette Delaloge. Efficacy of Platinum-based first-line chemotherapy among metastatic breast cancer (MBC) patients according to the germline BRCA1/2 mutational status: An analysis of the French ESME MBC database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-11.

Abstract PD10-08: Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016

Abstract BACKGROUND: Approximately 5% of breast cancer (BC) patients (pts) carry a deleterious germline BRCA mutation (gBRCAm). Retrospective studies suggest that overall survival (OS) is equivalent between gBRCAm carriers and non-carriers with metastatic BC (MBC). We aimed to use the large ESME multicentre national MBC database to compare outcomes of gBRCAm carriers, gBRCA wild-type (WT) and not tested (NT) pts. METHODS: We used the large ESME MBC database (NCT03275311), a unique national cohort of all consecutive pts who initiated a first-line treatment for MBC between 2008 and 2016 in one of the 18 French Comprehensive Cancer Centers. All pts with data available regarding gBRCA testing were selected for the present analysis. 26 pts with non-BRCA germline mutations were classified in the WT group. The primary endpoint was OS from date of treatment initiation in the 3 groups of patients: gBRCAm, gBRCA WT and gBRCA NT.Secondary endpoints were progression-free survival under first line treatment (PFS1), clinical and biological characteristics of the 3 groups and prognostic factors for OS. Multivariable analyses included the main known prognostic factors (age at MBC, MBC subtype, disease-free interval, presence of visceral disease, number of metastatic sites). They were conducted using Cox proportional analyses. RESULTS: 20624 pts were included in this analysis (414 gBRCAm, 1710 WT, 18500 gBRCA NT). Pts and disease characteristics are summarized in table 1. As expected, patients with gBRCAm were younger and had a higher rate of TNBC and G3 tumors. Median follow-up was 50.5 months (95%CI 49.7-51.5). Non-adjusted median OS was 30.6 months [21.9-34.3] in the gBRCAm group, 35.8 [32.2-37.8] in the WT and 39.3 [38.3-40.3] in NT groups. Median PFS1 was 7.9 months [6.6-9.3] in the gBRCAm group, 7.8 [7.3-8.5] in the WT and 9.7 months [ 9.5-10.0] in the NT groups. In multivariable analyses, OS and PFS were not significantly different between MBC patients with gBRCA and others (respective HRs 1.01 [0.88;1.17], p=0.87 and 0.94 [0.84;1.06], p=0.31). CONCLUSION: In this large scale real-life ESME MBC database analysis, outcomes of gBRCAm carriers with MBC do not differ from non carriers or not tested subgroups, when adjusted for other prognostic factors. Table 1: characteristics of patients and diseasegBRCAm. gBRCA WT. gBRCA NT Pvalue (chi-2)N = 414 N = 1710 N = 18500 Age (years) median [range]45 [23-82]48 [20- 88]61 [22-103]p<0.0001Grade 3 N (%) Missing data202 (57.7) 64598 (41.1) 2545337 (34.5)3036p<0.0001Triple negative breast cancer N (%)158 (38.2)370 (21.6)2331 (12.6)p<0.0001De novo MBC N (%)74 (17.9)359 (21)5914 (32)p<0.0001Disease-free interval (months) median [range]39.0 [-1.5- 425.7]36.3 [-2.1- 549.6]31.8 [-2.9- 657.8]p<0.0001Metastatic sites ≥3 N (%)113 (27.3)349 (20.4)3943 (21.3)p=0.008Visceral metastases N (%)279 (67.4)964 (56.4)10659(57.6)p=0.0002Central Nervous System Metastases N (%)66 (15.9)132 (7.7)1145 (6.2)p<0.0001 Citation Format: Audrey Mailliez, Veronique D'Hondt, Amelie Lusque, Olivier Caron, Luc Cabel, Antony Goncalves, Marc Debled, Laurence Gladieff, Jean-Marc Ferrero, Thierry Petit, Marie-Ange Mouret-Reynier, Jean-Christophe Eymard, Jean-Sébastien Frenel, Thibault De La Motte Rouge, Gaëtane Simon, Suzette Delaloge. Outcomes of germline BRCA carriers versus non-carriers in the french national metastatic breast cancer ESME cohort 2008-2016 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-08.

Outcome beyond third-line chemotherapy for metastatic triple-negative breast cancer in the French ESME program

PurposeAmong metastatic breast cancer (MBC) patients, those with a triple-negative breast cancer phenotype (mTNBC) have the worst prognosis, but the benefit of chemotherapy beyond second line on outcome remains uncertain. The purpose of this study was to identify predictive factors of outcome after third- or fourth-line chemotherapy. MethodsThe ESME-MBC database is a French prospective real-life cohort with homogeneous data collection, including patients who initiated first-line treatment for MBC (2008–2016) in 18 cancer centers. After selection of mTNBC cases, we searched for independent predictive factors (Cox proportional-hazards regression models) for overall survival (OS) on third- and fourth-line chemotherapy (OS3, OS4). We built prognostic nomograms based on the main prognostic factors identified. ResultsOf the 22,266 MBC cases in the ESME cohort, 2903 were mTNBC, 1074 (37%) and 598 (20%) of which had received at least 3 or 4 lines of chemotherapy. PFS after first- and second-line chemotherapy (PFS1, PFS2) and number of metastatic sites ≥3 at baseline were identified by multivariate analysis as prognostic factors for both OS3 (HR = 0.76 95%CI[0.66–0.88], HR = 0.55 95%CI[0.46–0.65], HR = 1.36 95%CI[1.14–1.62], respectively), and OS4 (HR = 0.76 95%CI[0.63–0.91], HR = 0.56 95%CI[0.45–0.7], HR = 1.37 95%CI[1.07–1.74]), respectively. In addition, metastasis-free interval was identified as a prognostic factor for OS3 (p = 0.01), while PFS3 influenced OS4 (HR = 0.75 95%CI[0.57–0.98]). Nomograms predicting OS3 and OS4 achieved a C-index of 0.62 and 0.61, respectively. ConclusionThe duration of each previous PFS is a major prognostic factor for OS in mTNBC patients receiving third- or fourth-line chemotherapy. The clinical utility of nomograms including this information was not demonstrated.

Lack of access to CDK4/6 inhibitors for premenopausal patients with metastatic breast cancer in Brazil: estimation of the number of premature deaths.

PurposeA CDK4/6 inhibitor (CDK4/6i) combined with endocrine therapy is the standard of care for patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) metastatic breast cancer (MBC). However, the incorporation of these agents into clinical practice remains challenging. This study aims to estimate the impact of the lack of access to ribociclib on mortality of premenopausal patients with MBC in Brazil.MethodsBased on published epidemiological studies and national cancer registries, we estimated the number of premenopausal patients with potential indication of ribociclib as first-line treatment for MBC. Efficacy estimates were based on results from the Monaleesa-7 trial. Our analysis is made under the unrealistic assumption that all premenopausal MBC patients would be candidates for the treatment. To estimate the number of yearly premature deaths that could be prevented, we considered the largest absolute effect on mortality when sequentially applying the observed hazard ratio.ResultsWe estimated an annual incidence of 4,294 premenopausal HR+, HER2- MBC patients in Brazil. Considering these patients, at 12, 24 and 60 months, the number of surviving subjects would be 3,504, 2,859 and 1,553 for endocrine therapy (ET) alone; and 3,717, 3,217 and 2,086 for ET plus ribociclib. The largest difference between both groups was observed at the end of the sixth year when the use of ribociclib would prevent 538 premature deaths (survival of 1,805 versus 1,267 patients by the 72nd month).ConclusionWe estimate that lack of access to CDK4/6i for patients with HR+, HER2-, MBC will cause the premature death of a significant number of premenopausal women with MBC. The unavailability of effective therapies has measurable consequences. Progress in this area demands a concerted effort to prevent further loss of lives.

Pyrotinib with trastuzumab and aromatase inhibitors as first-line treatment for HER2 positive and hormone receptor positive metastatic or locally advanced breast cancer: study protocol of a randomized controlled trial

BackgroundHER2 dual-blockade combined with aromatase inhibitors (AI) is a promising strategy to improve progression-free survival (PFS) in hormone receptor (HR) positive, metastatic breast cancer (MBC). Pyrotinib is a novel irreversible epidermal growth factor receptor/HER2 dual tyrosine kinase inhibitor. However, there is scarcity of data on the effectiveness and safety of pyrotinib combined with trastuzumab and AI as first-line treatment in a metastatic setting.Methods/designThe present study is a prospective, randomized, open-label trial. 198 patients with HER2+/HR+ MBC will be recruited. Eligible patients will be allocated (2:1) to either an experimental group (pyrotinib + trastuzumab + AI) or a control group (trastuzumab + AI). Allocation will be stratified by 1) time since adjuvant hormone therapy (≤ 12 months/> 12 months/no prior hormone therapy); 2) lesion sites (visceral / non-visceral). The primary endpoint is PFS.DiscussionTo our knowledge, this is the first prospective randomized controlled trial to assess dual HER2-blockade with pyrotinib in the metastatic setting. This study will provide valuable evidence regarding the efficacy and safety of pyrotinib when combined with trastuzumab and an AI as first-line treatment for MBC. Moreover, it will also evaluate the feasibility of endocrine therapy as an alternative to chemotherapy in providing de-escalation therapy with less toxicity for advanced HR+/HER2+ patients.Trial registrationClinicalTrials.gov, ID: NCT03910712. Registered on 10 Apr. 2019.

Abstract P6-11-14: Poor overall survival in women with de novo metastatic breast cancer: Does this reflect a lack of access to healthcare?

Abstract Introduction: Due to its epidemiological and therapeutic aspects, metastatic breast cancer (MBC) is a highly relevant clinical condition. Currently, most of the data on MBC originate from retrospective, hospital-based studies or controlled trials involving specific populations and treatments. On the other hand, population-based studies have the advantage of enabling an epidemiological analysis to be made of different populations, which may help in the development of specific public policies. This study aimed to estimate overall survival in women diagnosed with de novo MBC in the city of Goiânia, Brazil. Methods: Cases were identified at the Goiânia population-based cancer registry between 1995 and 2011. All women with metastatic disease at diagnosis were included in the study. The clinical and demographic characteristics of the sample and data related to the diagnosis and treatment of the disease were collected. Variables not recorded systematically in the cancer registry were collected directly from medical records. The distribution of survival was calculated using the Kaplan-Meier estimator and compared between the groups using the log-rank test, with 95% confidence intervals. Cox regression analysis was used for the multivariate analysis, with the variables being adjusted according to hormone receptor expression. P-values < 0.05 were considered statistically significant. Results: Over the 16-year period covered by the study, 5,289 cases of breast cancer occurred in residents of Goiânia, Brazil. Of these, 277 women (5.2%) had MBC. Mean age at diagnosis was 54.7 (±14.5) years. Overall survival at 60 and 120 months was 19.9% and 7.7%, respectively. In the group of patients with hormone receptor-positive cancer, endocrine therapy was prescribed in 14.0% of cases (6/43) as first-line treatment for MBC and in 48.5% (17/35) as second-line treatment. Of the 23 women with HER2-positive breast cancer for whom data were available on the treatment received, three had received trastuzumab as first-line treatment and two as second-line treatment. In the univariate analysis of 5-year overall survival, the following factors were found to be statistically significant: staging (T) (p=0.01); histological type (p=0.02), histological grade (p=0.03), estrogen receptor status (p=0.02), progesterone receptor status (p<0.001), tumor phenotype (p=0.02), type of healthcare (p=0.04), whether breast surgery had been performed (p<0.001) and the initial site of metastases (p=0.02). In the group of patients with hormone receptor-positive tumors, there was no difference in survival as a function of the type of first-line treatment received (chemotherapy versus endocrine therapy). In the 5-year multivariate analysis adjusted for hormone receptor status, the type of healthcare (p=0.01) and whether breast surgery was performed (p=0.03) remained statistically significant. Conclusion: This is the first population-based study dealing with MBC in Brazil. Overall survival was low in this population, and lower than rates found in specialist centers in Brazil and in developed countries. Increasing access to diagnosis and treatment could increase the likelihood of survival in patients with MBC treated in the public healthcare system. Table 1. Overall survival in women with de novo metastatic breast cancer in the city of Goiânia, Brazil, by the type of healthcare (1995-2011).Health carePublicPrivateTotal*5-year survival (%)6.922.4128*Survival (months)19.727.221.9Events81 (90.0)28 (73.3)109 (85.2) Citation Format: Leonardo Ribeiro Soares, Ruffo Freitas-Junior, Edesio Martins, Jose C Oliveira, Maria P Curado. Poor overall survival in women with de novo metastatic breast cancer: Does this reflect a lack of access to healthcare? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-14.

Abstract PD1-04: Results of a phase II double-blinded, randomized, placebo-controlled clinical trial of Indoximod, an Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, in combination with Taxane chemotherapy in metastatic breast cancer (MBC)

Abstract Background: IDO1 is a mediator of tumor immune suppression through alteration of tryptophan metabolism. Indoximod (1-methyl-tryptophan) is an IDO1 pathway inhibitor. There is preclinical evidence that indoximod acts synergistically with chemotherapy such as taxanes (Uyttenhove, 2003) in an immune dependent fashion. Previous studies demonstrated the safety and activity of indoximod combined with docetaxel in patients with advanced solid tumors, including breast cancer (Soliman, 2014). A phase 2 clinical trial was designed to study the efficacy of indoximod plus taxanes in metastatic breast cancer (MBC) patients (pts). Method: This is a phase II randomized, 1:1 placebo controlled clinical trial, that enrolled MBC pts in multiple centers in the US and Poland. Eligibility criteria included ER+ or ER- HER2- MBC, ability to receive taxane therapy, PS 0-1, normal organ function and absence of autoimmune disease. Pts were randomized to taxane (either weekly paclitaxel 80mg/m2 3 on 1 off or q3wk docetaxel at 75mg/m2 per treating physician’s discretion) + placebo (TP) or taxane + indoximod 1200mg PO BID (TI) as first line treatment for MBC. Primary endpoint was PFS. The sample size of 154 patients was designed to detect a HR of .64 with one sided α=.1 and β=.2 after 95 events. Archival tumor tissue was stained with IHC for IDO1 expression when available. Aperio digital pathology positive pixel algorithm was used for scoring, with manual verification. Median value was used as cut-off for IDO positivity. Results: 164 pts were randomized and treated (85 TI, 79 TP). Demographics and tumor features are shown in table 1. Treatment discontinuation was due to disease progression (60%), adverse events (10%), other (30%). Objective response rate was 40% in TI and 37% in TP arm (p=.74). The median PFS was 6.0 (95% CI, 4.5, 8.1) months in the TI arm and 8.4 (95% CI, 5.6, 9.8) in the TP arm, HR of 1.14 (0.81, 1.60). The median OS was 21.6 months (CI 95%, 16, 39.1) in the TI arm and 21.2 (CI 95%, 19.1, 32.1) in the TP arm. The median follow up was 17.4 (range 0.1, 39.4) months. Grade ≥3 treatment emergent adverse events were observed in 60% of patients in both arms with neutropenia, fatigue, anemia, diarrhea being most common but not significantly different between arms. An exploratory analysis of IDO staining with outcomes in 42 samples (22 in TI and 20 TP) suggested a difference in median PFS in pts with high IDO expression assigned to TI vs. TP (10.3 vs 4 months, p=.047). No other prognostic or predictive associations were observed based on IDO status in the analysis. Conclusions: The combination of indoximod with a taxane in 1st line HER2- MBC was safe and did not result in added toxicity. In an unselected population, no improvement in clinical outcomes was observed for the combination over taxane alone. However, higher tumor IDO expression may select for MBC pts who benefit more from indoximod and should be investigated as a predictive biomarker in future studies. Demographics and tumor featuresIndoximodPlaceboOverallParameterStatistic(N=85)(N=79)(N=164)Age (years)n8579164median (min, max)58 (29,76)57 (29,85)58 (29,85)GenderMalen (%)1 (1.2)2 (2.5)3 (1.8)Femalen (%)84 (98.8)77 (97.5)161 (98.2)RaceWhiten (%)71 (83.5)66 (83.5)137 (83.5)African Americann (%)12 (14.1)10 (12.7)22 (13.4)Asiann (%)1 (1.2)01 (0.6)Othern (%)1 (1.2)3 (3.8)4 (2.4)ECOG status0n (%)41 (48.8)43 (54.4)84 (51.5)1n (%)44 (52.2)36 (44.3)80 (46.6)Hormone Receptor StatusNegativen (%)23 (27.1)23 (29.1)46 (28.0)Positiven (%)62 (72.9)56 (70.9)118 (72.0)Choice of TaxaneDocetaxeln (%)62 (72.9)59 (74.7)121 (73.8)Paclitaxeln (%)23 (27.1)20 (25.3)43 (26.2) Citation Format: Veronica Mariotti, Shou-Ching Tang, Patrick Dillon, Alberto Montero, Andrew Poklepovic, Susan Melin, Ibrahim Nuhad, Petros Nikolinakos, Eugene Kennedy, Hyo Han, Roohi Ismail-Khan, Daniel Bruetman, Oana Danciu, Paul Gilman, Boguslawa Karaszewska, Krzysztof Lesniewski-Kmak, Timothy Panella, Dhimant Patel, Malgorzata Suszko-Kazarnowicz, Fabio Volterra, Hatem Soliman. Results of a phase II double-blinded, randomized, placebo-controlled clinical trial of Indoximod, an Indoleamine-2,3-dioxygenase 1 (IDO1) inhibitor, in combination with Taxane chemotherapy in metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD1-04.

Abstract P1-19-19: Treatments and outcome in older versus younger women with HER2-positive metastatic breast cancer in the multicenter national observational ESME database

Abstract Background: Prognosis of women with HER2+ metastatic breast cancer (MBC) has radically improved over the past 10 years, resulting from the implementation in clinical of anti-HER2 therapies. However, there are limited data regarding these trends in the older women, although they represent a growing segment of the population. Standard strategy being based mostly on combinations of anti-HER2 treatments with chemotherapy, under-treatment may be a specific issue in this population. Methods: Based on the ESME MBC Data Platform (NCT03275311),a unique national real-life database including individual data from all patients (pts) ≥18 years who initiated a first-line treatment for MBC between 2008 and 2016 in the 18 French Comprehensive Cancer Centers, the main objective of this work was the description of patients’ outcome in women with HER2+ MBC according to age: ≥70 vs <70. Secondary objective included the description of treatment patterns and a multivariate analysis. Outcome was described with overall survival (OS) and progression-free survival (PFS). Variables of interest were age (≥70 vs < 70), number of metastatic sites at initial MBC diagnosis (1 vs 2 vs ≥3), visceral disease (Y/N), hormone receptor status (HR+/HR-), de novo MBC (Y/N), type of first-line treatment. We relied on Cox’s proportional hazard (PH) model, with adjustment for non-PH in the presence of time-varying effects; hazard ratios (HR) with 95% confidence interval were reported (IC95%). Results: Of 22463 cases selected, 4045 (18%) women had HER2+ MBC with a 4.4-year median follow-up. Of those, 814 (20%) were aged ≥ 70 and had more often HR+ disease (Table 1). As 1st line treatment, anti-HER2 therapy was prescribed in 76% vs 92% of older vs younger pts, combined with chemotherapy in 65% vs 89%. Median OS and PFS (years) were 2.9 [2.6-3.1] and 0.9 [0.8 - 1.0] vs 4.5 [4.2-4.6] and 1.1 [1.1-1.2] in older vs younger patients. Multivariate analysis for OS identified the following variables as significant: age ≥ 70 (HR=1.57 IC95% [1.40-1.75]), 2 and ≥ 3 metastatic sites (HR=1.24 IC95% [1.10-1.39] and HR=1.92 IC95% [1.70-2.17] respectively), de novo MBC (HR 0.70 IC95% [0.63 - 0.77]), visceral disease with a time-varying effect (HR=2.67 IC95% [2.11-3.39] and 5.98 IC95% [4.64-7.46] at 1 and 5 years) and first-line treatment with a time-varying effect, better prognosis for combination of chemotherapy + anti-HER2 agent + endocrine therapy vs any other. Except for de novo MBC, similar results were observed for PFS. Conclusions: In this large real-life database, older HER2+ MBC patients received significantly less frequently “standard” first-line anti-HER2 treatment, defined as a combination of chemotherapy and anti-HER2 treatment. Age was a strong risk factor for both PFS and OS. Given the lack of information on geriatric assessment (e.g. general health status, functional status, comorbidity, etc.), confounding factors and usual selection biases cannot be ruled out. These results stress the importance to study older populations with specific approaches, not based on the usual transfer of those developed in younger ones, in order to avoid under and overtreatments, both that are not acceptable. Table 1: Patients’ characteristics and first-line treatment≥70<70AllP value N814 (20%)3231 (80%)4045 (100%)NAAge at MBC diagnosis (years)median775357NAQ1-Q373-8245-6047-67HR+ (≥10%)Yes560 (69%)2034 (63%)2594 (64%)0.01No247 (30%)1167 (36.1%)1414 (35%)missing7 (1%)30 (1%)37 (1%)De novo MBCYes310 (38%)1310 (41%)1620 (40%)0.20No503 (62%)1915 (59%)2418 (60%)missing1 (0%)6 (0%)7 (0%)Number of metastatic sites1429 (53%)1670 (52%)2099 (52%)0.902211 (36%)834 (26%)1045 (26%)3+170 (21%)696 (21%)866 (21%)missing4 (0%)31 (1%)35 (1%)Visceral diseaseYes510 (63%)2096 (65%)2606 (64%)0.18No300 (37%)1104 (34%)1404 (35%)Missing4 (0%)31 (1%)35 (1%)Chemotherapy + anti-HER2 agent as 1st line treatmentYes529 (65%)2880 (89%)3409 (84%)<0.01No241 (30%)296 (9%)537 (13%)Missing44 (5%)55 (2%)99 (2%)Anti-HER2 agent as 1st line treatmentYes623 (76%)2984 (92%)3607 (89%)<0.01No147 (18%)192 (6%)339 (8%)Missing44 (6%)55 (2%)99 (3%) Citation Format: Mylène Annonay, Morgane Abiven, Etienne Brain, Mony Ung, Laurence Cristol-Dalstein, Marie-Ange Mouret-Reynier, Anthony Goncalves, Sophie Abadie-Lacourtoisie, Eric Francois, Claudia Lefeuvre-Plesse, Johann Le Fel, Veronique Lorgis, Veronique Servent, Lionel Uwer, Christelle Jouannaud, Marianne Leheurteur, Loic Campion, Coralie Courtinard, Olivier Villacroux, Thierry Petit, Pierre Soubeyran, Thomas Bachelot, Carine Bellera, Suzette Delaloge. Treatments and outcome in older versus younger women with HER2-positive metastatic breast cancer in the multicenter national observational ESME database [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-19.

Oral vinorelbine versus intravenous vinorelbine, in combination with epirubicin as first-line chemotherapy in Chinese patients with metastatic breast cancer

Oral VRL offers easier administration, better quality of life, and cost saving. This study aimed to evaluate the treatment efficacy in terms of tumor response of the two formulations of vinorelbine (VRL, oral and IV) in combination with epirubicin (EPI); and the effect of EPI co-administration on VRL pharmacokinetics (PK) in Chinese patients with metastatic breast cancer (MBC) using a phase 2, open label, randomized trial. Patients were aged 18–70 years, had histologically confirmed MBC, Karnofsky Performance Status ≥ 70%, and life expectancy ≥ 12 weeks. The treatment consisted of 6 cycles of 3 weeks each. VRL dose was: (Oral-VRL) 60 mg/m2 for cycle 1, 80 mg/m2 for cycles 2–6, and (IV-VRL) 25 mg/m2 for cycle 1 and 30 mg/m2 for cycles 2–6. EPI dose of 75 mg/m2 was given on day 1 in both arms for all cycles. 133 patients were enrolled: 66 in Oral-VRL and 67 in IV-VRL arms. The median age for Oral-VRL and IV-VRL arms was 48.4 and 50.0 years, respectively. Objective response rates were 50.0% (95% CI 37.4–62.6%) for Oral-VRL and 53.7% (95% CI 41.1–66.0%) for IV-VRL. Both treatment arms met the efficacy objective target of at least 31 responses, demonstrating efficacy as first-line treatment for MBC. Similar blood PK profiles, exposures, and VRL clearance were observed between VRL + EPI vs VRL-only modalities for both arms. Oral VRL is comparable to IV VRL and an effective first-line treatment for Chinese patients with MBC. The activity of VRL + EPI combination is unaltered when VRL is given orally at recommended doses.

Abstract P1-14-07: Randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for metastatic breast cancer (SELECT BC-CONFIRM)–A combined analysis of two randomized phase 3 studies (SELECT BC-CONFIRM and SELECT BC)–

Abstract Background: Anthracycline-containing regimens and taxane have been standard as the first-line chemotherapy for metastatic breast cancer (MBC). We conducted SELECT BC (randomized phase 3 study of taxane versus S-1 as first-line treatment for MBC) for evaluating the efficacy of S-1 for patients with HER2-negative MBC from 2006 to 2010 in Japan. This study demonstrated non-inferiority of S-1 in overall survival (OS) (median OS was 37.2 months in taxes group and 35.0 months in S-1 group (HR 1.05, 95% CI 0.86–1.27, p=0.015)), and superiority in health-related quality of life (HRQOL) to taxanes. S-1 was also shown as less toxic than taxane (Lancet Oncol 2016; 17: 90-98). S-1 might provide clinical benefit as first-line treatment for patients with HER2-negative MBC. To confirm this suggestion, we have conducted further study (randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for HER2-negative MBC: SELECT BC-CONFIRM) from 2011 to present, and a combined analysis of two randomized studies (SELECT-BC CONFIRM and SELECT-BC). Methods: In SELECT BC-CONFIRM, 230 patients receiving first-line treatment for MBC were randomly assigned to either anthracycline group (n=115) or S-1 group (n=115). Anthracycline group patients received anthracycline-containing regimens (AC, EC, FAC, FEC, q3w) at the discretion of the treating physician. S-1 group patients received S-1 40–60 mg twice daily based on the patient's body surface area for 28 days on, 14-day off. The primary endpoint was OS, and secondary endpoints were progression-free survival (PFS), time to treatment failure (TTF), adverse events, HRQOL, and cost-effectiveness. The results were combined with SELECT-BC, to confirm the hypothesis that S-1 treatment is not inferior to the standard therapy (taxanes / anthracycline) for HER2-negative MBC. Results: A combined analysis of the two studies showed that HR was 1.06, 95%CI 0.90-1.253, and p=0.0071 between the standard therapy group and S-1 group. In addition, the Bayesian posterior probability for which HR would be less than 1.333 was about 99.6%. Conclusions: A combined analysis of SELECT BC-CONFIRM and SELECT BC clearly demonstrated that OS with S-1 was not inferior to that with the standard therapy in patients receiving first-line treatment for HER2-negative MBC. S-1 could become a standard therapy for this patient population. Citation Format: Park Y, Akabane H, Watanabe T, Takahashi M, Sagara Y, Nishimura R, Tsurutani J, Takashima T, Fujisawa T, Hozumi Y, Uemura Y, Mukai H. Randomized phase 3 study of anthracycline-containing regimens versus S-1 as first-line treatment for metastatic breast cancer (SELECT BC-CONFIRM)–A combined analysis of two randomized phase 3 studies (SELECT BC-CONFIRM and SELECT BC)– [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-14-07.

Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic breast cancer

Ribociclib is a CDK4-6 inhibitor recently approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as first-line treatment for metastatic breast cancer (MBC). The pivotal trial showed a significant improvement in progression-free survival when compared to endocrine therapy alone. However, having a challenging toxicity profile in comparison with exclusive endocrine therapy, safety may be a concern when combined to radiotherapy (RT) with palliative approach.There are no available published data regarding the combination of ribociclib and palliative RT. We reported our preliminary experience on the first five patients treated at the Radiation Oncology Unit of the Florence University (Florence, Italy) giving palliative RT concomitant to ribociclib plus letrozole as first-line treatment for MBC.

PP118 Cardiac Safety Of Trastuzumab For Metastatatic Breast Cancer

Introduction:Metastatic breast cancer (MBC) is considered incurable. Trastuzumab (T), a monoclonal antibody that blocks HER-2 is used in combination with other chemotherapies or as monotherapy to treat various stages of breast cancer, including MBC. The aim of this study was to evaluate the safety of T as first line treatment or after progression in women with MBC.Methods:We conducted a systematic review of randomized controlled trials. We searched the databases: MEDLINE (Pubmed), LILACS, Cochrane Library and EMBASE (accessed November 2016) and performed manual search. The methodological quality assessment was performed using the Cochrane Collaboration risk of bias tool. We adopted the random effects model for meta-analysis. The results were presented as relative risk (RR) with 95% confidence intervals.Results:The search retrieved 2,238 publications. After eligibility criteria assessment we included five studies on T in the first line treatment (T n = 493; no-T n = 492) and two studies on T after progression (T n = 226; no-T n = 226). In general, studies presented moderate quality. Five were funded by the pharmaceutical industry. Regarding first line treatment, the group of patients that used T had three times higher risk of developing cardiac adverse event compared to the group that did not use T (RR = 3.3; 95% CI: 1.52 − 7.29; I2 = 0%, p = 0.39). The continuity of T after progression revealed no difference between the groups regarding the risk of developing cardiac adverse event (RR = 5.31; 95% CI: 0.62 − 45.49; I2 = 0%, p = 0.62).Conclusions:The evidence regarding the higher risk of cardiac adverse event with T as first line treatment for MBC is robust and this should be taken into account when balancing risks and benefits of treatment. The evidence for continuation of T after MCB progression is week and more studies are needed to confirm the findings.