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Background: The phase III Monaleesa-2, Monaleesa-3 and Monaleesa-7 trials have shown significantly improved PFS for the combination ribociclib + ET vs ET + placebo in pre-, peri-, and postmenopausal women with HR+/HER2–, first and second line aBC. The Compleement-1 trial is a phase IIIb, single-arm, open-label, international study to assess the safety and efficacy of ribociclib + letrozole in men and women who have not received prior ET for HR+, HER2– ABC [J Clin Oncol 36, 2018 (suppl; abstr 1056)]. Methods: 526 patients with HR+, HER2– ABC, ≤1 line of prior CT, and no prior ET for aBC were enrolled in the Compleement-1trial in Spain from April 2017 to January 2018. Patients received ribociclib (600 mg/day, 3 weeks on/1 week off) + letrozole (2.5 mg/day); men and premenopausal women received concomitant goserelin (3.6 mg subcutaneous implant every 28 days). The primary objective was safety and tolerability. Here we report on a sub-analysis from the Spanish population of Compleement-1 trial including baseline characteristics and early safety results for the first patients enrolled who completed at least 56 days of follow-up or discontinued before the cut-off date (3rd Oct 2017). Results: One hundred fifty four patients constituted the analytical cohort for this sub-analysis. Demographics and baseline characteristics: median age was 52 years (range 24-82); 1% of patients were male, 31.8% female pre-menopausal and 67.5% female post-menopausal; 44.2% vs 38.3% of patients had visceral disease vs bone only disease; 49.9% patients had ≥2 metastatic sites; and 34.4% of patients presented as de novo stage IV. The median exposure for study treatment was 1.8 months (range 0.8-1.8). The grade 3/4 events reported >1% included neutropenia (50%), increased GGT levels (3.2%), leukopenia (1.3%), and increased ALT (1.3%). QTcF prolongation >480ms based on ECG data was reported in 1.2% patients. Median dose intensity for ribociclib was 600mg/day (range 476.5-600); 11% of patients required one dose reduction (8.4% due to AEs), 59.7% had at least one dose interruption (57.1% due to AEs) and 9.7% were permanently discontinued (4.5% due to AEs). Conclusions: Preliminary safety results from this Compleement-1 sub-analysis including Spanish population are consistent with previous data presented from Monaleesa-2, Monaleesa-3, Monaleesa-7 and Compleement-1. These data support the predictable and manageable safety profile of ribociclib in combination with letrozole. Clinical trial information: NCT02941926 Citation Format: Salvador J, Ciruelos EM, Prat A, Jiménez-Rodríguez B, de la Cruz L, Martínez N, Villanueva Vázquez R, de Toro R, Antón A, Moreno F, Alvarez I, Gavila J, Quiroga V, Vicente E, de la Haba J, González-Santiago S, Díaz N, Barnadas A, Cantos Sánchez de Ibargüen B, Delgado JI, Bellet M, Gimeno A, Sanz S, Martin M. Ribociclib + letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (aBC) with no prior endocrine therapy (ET) for ABC: CompLEEment-1 trial, preliminary results from Spanish population [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 P6-18-17.

Background: The oral AKT inhibitor IPAT is being evaluated in cancers with a high prevalence of PI3K/AKT pathway activation. In the PBO-controlled randomized phase II FAIRLANE trial (NCT02301988), adding IPAT to PAC as neoadjuvant therapy for TNBC led to a numerical increase in pathologic complete response (pCR) in unselected patients (17.1% vs 13.3%), with a greater treatment effect in patients with PIK3CA/AKT1/PTEN-altered tumors (17.9% vs 11.8%). The addition of IPAT also led to an increase in complete response (CR) by MRI (27.6% vs 13.3%) that was enhanced in patients with PIK3CA/AKT1/PTEN-altered tumors (39.3% vs 8.8%) [Oliveira, AACR 2018]. We report an exploratory analysis performed to provide better understanding of potential biomarkers for response. Methods: Pretreatment tumor samples were evaluated for genomic alterations using the FoundationOne® (Foundation Medicine) assay (n=144) and gene expression by RNA-Seq (n=92). Samples were classified into TNBC subtypes based on the method developed by Lehmann and Pietenpol [Lehmann, J Clin Invest 2011]. Tumor-infiltrating lymphocytes (TILs) were quantified using the Salgado method [Salgado, Ann Oncol 2015] (n=135). Results: Of 62 patients (43%) with PIK3CA/AKT1/PTEN-altered tumors, 21 had an activating mutation in PIK3CA or AKT1 and 47 had an alteration in PTEN (6 [3 in each arm] had both PIK3CA mutation and PTEN alteration). Although only 3 patients with PIK3CA/AKT1-mutant tumors achieved a pCR, there was an increased rate of MRI CR with the addition of IPAT to PAC [Table]. In patients with PTEN alterations, both pCR rate and MRI CR rate were increased with IPAT. In patients treated with PBO + PAC, all 4 pCR patients evaluable by RNA-Seq were of the immunomodulatory (IM) subtype. However, in the IPAT + PAC arm, pCRs were also seen in patients with basal-like 1 (BL-1), mesenchymal (M), and mesenchymal stem-like (MSL) subtypes. Consistent with this observation, in the PBO + PAC arm, samples from patients achieving a pCR had significantly higher levels of stromal TILs than those from patients who did not have a pCR, while no difference was observed in the IPAT + PAC arm. Response, n (%)PIK3CA/AKT mutation (n=21)PTEN alteration (n=47) IPAT + PAC (n=11)PBO + PAC (n=10)IPAT + PAC (n=21)PBO + PAC (n=26)pCR1 (9%)2 (20%)4 (19%)3 (12%)CR by MRI5 (45%)1 (10%)8 (38%)2 (8%) Conclusions: This retrospective exploratory biomarker analysis of the phase II FAIRLANE trial of neoadjuvant IPAT for TNBC provides insight into the potential heterogeneity of response and resistance to taxane therapy. The results also hint that response to PAC alone is dependent on baseline immune infiltration and that this dependency might be relieved with the addition of AKT inhibition. Citation Format: Wongchenko MJ, Oliveira M, Saura C, Nuciforo P, Calvo I, Andersen J, Passos Coelho JI, Gil Gil M, Bermejo B, Patt DA, Ciruelos E, Singel SM, Maslyar DJ, Xu N, de la Peña L, Baselga J, Gendreau S, Isakoff SJ. Exploratory biomarker analyses of FAIRLANE, a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) + paclitaxel (PAC) for early triple-negative breast cancer (TNBC) [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 P2-08-19.

Background: Optimal endocrine therapy for premenopausal pts with early HR+ BC may depend on complete estrogen suppression with GnRH analog, which is crucial when using concurrent aromatase inhibitors (AIs). SOFT-EST is a prospective substudy of the phase 3 SOFT trial aiming to describe estradiol (E2), estrone (E1) and estrone sulphate (E1S) during the first 4 years (y) of monthly Trip+E/T and to assess if there were suboptimally estrogen suppressed (SES) pts in the E+Trip group. Secondary objectives included associations of baseline (BL) factors with SES, early SES with later SES, and SES with disease-free survival (DFS; exploratory objective). Methods: Patients from select centers who consented and enrolled in SOFT, selected Trip as ovarian function suppression method, and were randomized to E+Trip or T+Trip were eligible for SOFT-EST until the accrual goal (120 pts: 90 E+Trip; 30 T+Trip). Prem status for SOFT eligibility was based on local E2. Blood sampling timepoints were 0, 3, 6, 12, 18, 24, 36 & 48 months (m) until Trip stopped. Serum estrogens were measured centrally by high specificity/sensitivity GC/MSMS and were not available during the study. For 4y analyses, SES was defined as E2 levels >2.72 pg/mL in ≥2 post-BL samples (E2 levels not consistent with postmenopausal (PM) status on AIs [Smith IE, JCO 2006]), or vaginal bleeding >3m after Trip start, or pregnancy. We explored 2 additional cutoffs: >10 pg/mL (clearly inconsistent with PM status on AIs) and >20 pg/mL (inconsistent with GnRH analog-related PM status). The analysis is intention-to-treat based on E/T assignment; as-treated analyses are forthcoming. Results: From Mar 2009 to Jan 2011,109 pts (E/T=83/26) started Trip and had ≥2 samples drawn. In pts assigned E+Trip, median reductions from BL in E1, E2 and E1S were >95% at all timepoints and significantly lower than in T+Trip. Post-BL E2 geometric mean ranged 0.8-1.3 pg/mL in E+Trip and 16.5-18.3 pg/mL in T+Trip. 21 (25%), 11 (13%) and 6 (7%) pts assigned to E+Trip had E2>2.72, >10, and >20 pg/mL in ≥2 post BL samples or vaginal bleeding (n=3), respectively. Early SES [(≥1 E2 value >2.72 pg/mL or vaginal bleeding in the firsty] predicted later SES [≥1 E2 value >2.72 or vaginal bleeding thereafter (n=1); p Conclusions: Most pts on E+Trip had a profound E2 drop consistent with postmenopausal status on AI, but >20% assigned to E+Trip had ≥2 E2 values >2.72 pg/mL and 4% had vaginal bleeding, with those having higher E2, lower FSH/LH at BL being at higher risk. SES at 12m predicted subsequent SES. Few DFS events limit the ability to assess clinical relevance of SES with disease outcomes. BL characteristicsN-109Prior chemo60 (55%)Amenorrhea39 (36%)Age Citation Format: Bellet M, Gray K, Francis P, Láng I, Ciruelos E, Lluch A, Ángel Climent M, Catalán G, Avella A, Bohn U, González-Martin A, Zaman K, Ferrer R, Azaro A, Rajasekaran A, De la Peña L, Fleming G, Regan MM. Estrogen levels in premenopausal patients (pts) with hormone-receptor positive (HR+) early breast cancer (BC) receiving adjuvant triptorelin (Trip) plus exemestane (E) or tamoxifen (T) in the SOFT trial: SOFT-EST substudy final analysis [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 P4-14-01.

Background: Anthracycline and taxane-based chemotherapy is the standard treatment for high-risk breast cancer. However, conventional anthracyclines are not commonly used in elderly patients or those patients prone to cardiotoxicity and there is a potential risk leaving them undertreated. Pegylated liposomal doxorubicin (PLD) has comparable efficacy, but significantly less cardiotoxicity than conventional anthracyclines. We conducted a phase II trial to assess the efficacy and safety of a neoadjuvant chemotherapy (NC) based on PLD and paclitaxel (PTX) in this group of patients. The pathological complete response, breast conservative surgery (BCS) and safety data at a 35-month follow-up were published (Gil-Gil et al. Breast Cancer Res Treat 2015). Here we present the final analysis of 5-year overall survival (OS) and 5-year disease-free survival (DFS) and cardiac safety after 60 months of follow-up. Methods: Fifty patients with stage II (48%) and III (52%) breast cancer (seven cases were T4d) and with at least one risk factor for developing cardiotoxicity were included. NC schedule: PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 every 4 weeks for four cycles, followed by 80 mg/m2 weekly PTX for 12. Median age was 73 years old (84% were older than 65 years). Forty-eight (96%) of tumors were triple negative (TN). Secondary objectives included 5-year DFS, 5year OS and cardiac safety measured by a decrease in left ventricular ejection fraction (LVEF), electrocardiogram (ECG) anda cardiac questionnaire performed every 3 months during the first year, every 6 months year 2-3 and every 12 months year 4-5 of follow-up. Results: Forty-eight patients (96%) completed the 4 cycles of PLD plus CPM, while only 26 patients (52%) could complete the 12 weeks of PTX. Forty-six patients (92%) underwent surgery. After surgery: 27 patients received radiotherapy, 2 letrozole and 1 trastuzumab. The 5-year OS was 56% (95% CI 41.2-68.4) and the 5-year DFS was 54.4% [95% CI: 38.3-67.9].No significant decrease in LVEF was seen (mean baseline LVEF was 66.6 (52-86) and mean LVEF after 60 months was 66 (54.5-73). Four patients (8%) developed cardiotoxicity (in 2 cases G3). There were 5 non-cancer deaths (10%): 3 during treatment (all in patients > 80 years: a sudden death one month after surgery, a haemorrhagic stroke 30 days after completing chemotherapy and a non-neutropenic pneumonia); and 2 during follow-up (1 Amyotrophic Lateral Sclerosis and 1 intestinal ischemia). Conclusions: PLD followed by PTX as NC was feasible in a fragile population of patients who were not candidates for conventional doxorubicin. The 5 year DFS and 5 year OS in elderly patients with bulky TN tumors were similar tothe reported in the literature. This regimen could be an option for the neoadjuvant treatment of cardiotoxicity-prone patients or elderly patients who present high-risk breast cancer. Citation Format: Gil-Gil M, Bellet M, Morales S, Barnadas A, Manso L, Morilla Ruiz I, Azaro A, Ciruelos Gil E, Garcia Martínez E, Marínez N, Melé M, Soler T, Villagrasa P, Pernas S. SOLTI-0702 CAPRICE: Final results of a phase II study of pegylated liposomal doxorubicin plus cyclophosphamide followed by paclitaxel as neoadjuvant chemotherapy in elderly or cardiotoxicity-prone patients with high-risk breast cancer: 5-year overall survival disease free survival and late cardiac safety [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-15-06.

BACKGROUND Despite treatment advances, up to 50% of patients with advanced HER2+ BC develop BM (Zimmer. Cancer Rep. 2020). Patients with HER2+ BC with BM have a worse prognosis than patients without BM. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, median progression-free survival (PFS) of 19.4 and 18.1 mo, and median duration of response (DOR) of 20.8 and 16.9 mo (Modi. Cancer Res. 2021; Jerusalem. Ann Oncol. 2020). Here we describe a trial evaluating T-DXd in patients with previously treated advanced/metastatic HER2+ BC ±BM. DESIGN DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing T-DXd 5.4 mg/kg q3w efficacy and safety in patients with previously treated advanced/metastatic HER2+ BC ±BM that progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excluding patients with prior tucatinib). Patients (n=250/cohort) will be enrolled in cohort 1 (−BM at baseline) or 2 (+BM at baseline). BM must be untreated and not needing immediate local therapy or previously treated and stable or progressing. Primary endpoints are ORR (cohort 1) and PFS (cohort 2) (both by RECIST version 1.1 per ICR). Secondary endpoints are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL in both cohorts; incidence of new symptomatic CNS metastasis (CNSM) in cohort 1; and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM in cohort 2. This is an encore; the original presentation will be at The European Society for Medical Oncology 2021.

Background Pre-clinical data and initial results from clinical studies point to the added benefit of CDK4/6 inhibition when combined with anti-HER2 tx. The current study is designed to evaluate the added benefit of palbociclib when given in combination with anti-HER2 and endocrine tx maintenance in the 1st†line setting of metastatic HER2+HR+ breast cancer. Trial design PATINA is an international, open-label, pivotal Phase III study. Primary objective is to demonstrate that the combination of palbociclib with anti-HER2 plus endocrine tx is superior to anti-HER2 plus endocrine tx in prolonging PFS. Sample size is 496 pts. The study starts after completion of 6-8 cycles of chemotherapy-containing anti-HER2 tx for metastatic breast cancer in the 1st line setting. Pts are eligible provided they are without evidence of disease progression by local assessment (i.e. CR, PR or SD). To account for the need for less intense tx regimens for a subset of pts diagnosed with HER2+ER+ disease, clinicians may recommend the combination of trastuzumab with either a taxane or vinorelbine prior to study initiation. Clinicians might also choose a non-pertuzumab option for pts previously treated with pertuzumab in the neo(adjuvant) setting. Secondary objectives include measures of tumor control (OR, CBR, DOR), OS, safety and QOL. The translational science main objective is to compare PFS estimates according to PIK3CA mutation status assessed by cfDNA analysis. Endocrine tx options are AI or fulvestrant. Premenopausal pts must receive ovarian suppression. The study has a 90% power to detect a hazard ratio of 0.667 in favor of the palbociclib arm. Pts approached to participate in AFT-38 will be asked to indicate on the informed consent forms whether remaining biospecimens and clinical data from the control arm of the study can be shared with the Mastering Breast Cancer (MBC) Initiative. The overarching purpose of the MBC is to create a mechanism for understanding the natural history of metastatic breast cancer by cataloguing longitudinally studied tumor-specific markers and treatment effects. ClinicalTrials.gov Identifier: NCT02947685 Citation Format: Metzger-Filho O, Mandrekar S, Loibl S, Ciruelos E, Gianni L, Lim E, Miller K, Huang C, Koehler M, Francis P, Valagussa P, Goel S, Prat A, Goetz M, Loi S, Krop I, Carey L, Lanzillotti J, Winer E, Tripathy D, DeMichele A. PATINA: A randomized open label phase III trial to evaluate the efficacy and safety of palbociclib + anti HER2 therapy + endocrine therapy vs anti HER2 therapy + endocrine therapy after induction treatment for hormone receptor positive, HER2 positive metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT3-05-07.

The aim of this study is to evaluate the cost-effectiveness and impact of gene-expression assays (GEAs) on treatment decisions in a real-world setting of early-stage breast cancer (ESBC) patients. This is a regional, prospective study promoted by the Council Health Authorities in Madrid. Enrolment was offered to women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, node-negative or micrometastatic, stage I or II breast cancer from 21 hospitals in Madrid. Treatment recommendations were recorded before and after knowledge of tests results. An economic model compared the cost-effectiveness of treatment, guided by GEAs or by common prognostic factors. 907 tests (440 Oncotype DX® and 467 MammaPrint®) were performed between February 2012 and November 2014. Treatment recommendation changed in 42.6% of patients. The shift was predominantly from chemohormonal (CHT) to hormonal therapy (HT) alone, in 30.5% of patients. GEAs increased patients’ confidence in treatment decision making. Tumor grade, progesterone receptor positivity and Ki67 expression were associated with the likelihood of change from CHT to HT (P

Background It is uncertain if the addition of OFS to adjuvant endocrine therapy with T improves outcomes in premenopausal HR+ BC. The SOFT trial was designed to determine the value of OFS in women who remain premenopausal and are treated with T (OFS question) and also to test whether an AI improves outcome in premenopausal women with HR+ BC treated with OFS (AI question). In the combined analysis of the TEXT and SOFT trials (AI question), the group treated with the AI exemestane+OFS had a significantly better disease-free survival (DFS) than those with T+OFS. This abstract presents the results of the OFS question (n=2,045). Patients and Methods Between November 2003 and January 2011, the SOFT phase 3 trial randomized 3066 premenopausal women with HR+ BC to 5 years of adjuvant endocrine therapy with exemestane+OFS versus T+OFS versus T alone, with OFS initiated by choice of GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Prior chemotherapy was allowed, provided women had confirmed premenopausal estradiol levels within 8 months of completing chemotherapy. The primary end point was DFS which included invasive local, regional, distant and contralateral breast events, second non-breast malignancies and deaths without prior cancer. Because of a lower-than expected overall event rate and to ensure results within a reasonable time-frame, a protocol amendment in 2011 changed the originally event-driven analysis plan. The amendment (1) designated the comparison of T+OFS versus T alone as the primary analysis for SOFT (n=2045), recognizing that the statistical power for the original three pairwise comparisons would be substantially reduced and (2) specified that the primary analysis of T+OFS versus T be undertaken when median follow-up was at least 5 years. The comparison would be tested at the 2-sided 0.05 level with no interim analysis. Based on the projected number of events at the lower rates, the estimated power to detect hazard ratios of 0.75, 0.70, and 0.66 for the comparison would be 52%, 69%, and 80%. Results The SOFT trial completed planned patient enrollment with an international collaboration involving 426 centres from BIG and NABCG led by the International Breast Cancer Study Group (IBCSG). Numbers of patients randomized, randomization strata, and pt age are summarized in the Table. The database lock for the primary analysis of the OFS question will occur in September 2014 and the final analysis will be completed by October 15, 2014. SOFT Patients (%)Tamoxifen alone1021 (33%)Tamoxifen+OFS1024 (33%)Exemestane+OFS1021 (33%)* Prior Chemotherapy54%Lymph node positive35%Median age (% < 40 years)43 years (30%)*Patients randomized to Exemestane+OFS are not part of the current analysis Conclusions We will present the primary analysis of outcomes and toxicities by treatment for women randomized to receive T+OFS versus T and address the value of OFS in addition to T as adjuvant endocrine therapy for premenopausal women with HR+ BC. Citation Format: Aron Goldhirsch, Richard D Gelber, Prudence A Francis, Meredith M Regan, Gini F Fleming, Istvan Lang, Eva M Ciruelos, Meritxell Bellet, Herve Bonnefoi, Miguel A Climent, Lorenzo Pavesi, Harold J Burstein, Silvana Martino, Nancy E Davidson, Charles E Geyer Jr, Barbara A Walley, Robert E Coleman, Pierre Kerbrat, Manuela Rabaglio-Poretti, Alan S Coates. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-08.

Background Circulating tumour cells (CTC) may be a good biomarker to guide the management of patients with LAMBC (Cristofanilli, NEJM 2004). Detection of CTCs in peripheral blood is a simple procedure. Eribulin monotherapy has shown improved survival in patients with LAMBC that has progressed after 2 or 3 chemotherapy regimens (EMBRACE study). The aims of this study were to evaluate the kinetics of CTCs before and after eribulin treatment, and its correlation with clinical outcomes. Methods Patients received eribulin (1.23 mg/m2 on days 1 and 8 of every 21-day cycle) as third-line therapy until progression, unacceptable toxicity or withdrawal. CTCs were measured in 7.5ml of blood at baseline and after the second cycle of treatment. Cell counting was performed using the CellSearch System, Veridex. Cox proportional hazards regression modeling was used to identify independent prognostic factors for survival endpoints. Results Out of 59 eligible women (mean age 57.7 years), 58 (98.3%) had received previous taxanes and/or anthracyclines. Nearly all (98.3%) had HER2-negative tumors, 72% were positive for estrogens, 21% were triple-negative; 64.4% had liver metastasis and 57.6% bone metastasis. The mean number of administered cycles was 6.9 ± 5.4. Follow-up was performed in 54 patients, with 18.5% (n=10) partial response, 42.6% (n=23) stable disease, and 38.9% (n=21) progressive disease. Clinical benefit was achieved in 33 patients (61.1%). Median progression-free survival (PFS) was 5.13 months (95% CI 3.23, 8.90) and median overall survival (OS) was 13.6 months (95% CI 11.8, not reached). CTC levels were measured in 50 patients. The mean number of CTCs at baseline was 16.8 (IQR 0-21) and on cycle 2, 5.4 (IQR 0-8.5), p Conclusions Our study suggests there is a significant correlation between levels of CTCs and disease prognosis. Eribulin monotherapy was related to a significant reduction in CTCs. (EudraCT number 2013-001416-30). Keywords eribulin, metastatic, breast cancer, circulating tumour cells. Citation Format: Manso Sánchez L, Moreno Antón F, Izarzugaza Perón Y, Delgado Mingorance I, Borrega García P, Echarri González MJ, Martínez Jáñez N, López González A, Olier Garate C, Ballesteros García A, Chacón López-Muñiz I, Ciruelos Gil EM, García Sáenz JA, Paz-Ares Rodríguez L. High reduction of circulating tumour cells in HER2-negative locally advanced or metastatic breast cancer (LAMBC) patients treated with eribulin as third line chemotherapy (ONSITE study) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-07-21.

Background: The combined results of TEXT and SOFT, after 5.7 years median follow-up, found adjuvant E+OFS significantly improved disease-free survival (DFS) vs T+OFS in premenopausal women with HR+ BC (Pagani et al, NEJM 2014). Follow-up was immature for overall survival (OS). We report a planned update with visit cut-off of 31Dec16 after 9 years median follow-up. Methods: TEXT and SOFT enrolled premenopausal women with HR+ early BC from Nov 2003 to Apr 2011 (2660 TEXT, 3047 SOFT in the intention-to-treat populations). TEXT randomized women within 12wk of surgery to 5 yrs E+OFS vs T+OFS; chemotherapy (CT) was optional and concurrent with OFS. SOFT randomized women to 5 yrs E+OFS vs T+OFS vs T alone, within 12wk of surgery if no CT planned, or within 8mo of completing (neo)adjuvant CT after premenopausal status was (re-)established. OFS was by choice of 5yr GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Both trials were stratified by CT use. The primary endpoint was DFS: randomization until invasive local, regional, distant recurrence or contralateral breast; invasive second malignancy; death. Secondary endpoints included invasive breast cancer-free interval (BCFI), distant recurrence-free interval (DRFI) and OS. Stratified Cox models estimated hazard ratios; Kaplan-Meier method estimated 8yr endpoint rates. NCT00066703/NCT00066690. Results: DFS for patients assigned E+OFS (n=2346) continued to be significantly improved over T+OFS (n=2344): 8yr DFS was 86.8% vs. 82.8%. The 8yr BCFI was improved by 4.1% (89.3% vs 85.2%) and 8yr DRFI by 2.1% (91.8% vs 89.7%). There was no difference in OS in patients assigned E+OFS vs T+OFS: 93.4% vs 93.3% OS at 8yrs. For 1996 women without CT there have been 45 deaths, with 98% OS at 8yrs with both treatments. EndpointN. EventsHazard Ratio (95% CI) E+OFS vs T+OFSDFS7200.77 (0.67-0.90); P Overall toxicity was not significantly worse with E+OFS than with T+OFS (32% vs 31% grade 3-4 targeted AEs). Hot flashes, musculoskeletal symptoms and hypertension were the most frequent targeted grade 3-4 AEs. Overall, 15% of patients stopped all protocol-assigned treatment early. Patients assigned E+OFS had increased risk of assigned oral endocrine therapy cessation (25% vs 19% for patients assigned T+OFS by 4yrs) but not of triptorelin cessation (18% vs 19% by 4yrs, respectively). Conclusions: After 9 yrs median follow-up, adjuvant E+OFS, as compared with T+OFS, shows a sustained reduction of the risk of recurrence but did not improve overall survival. As in postmenopausal women, oncologists need to consider potential absolute benefits and properly select patients at sufficient risk for recurrence for whom E+OFS seems indicated. Follow-up continues, which will further clarify the effect of E+OFS for safety, late recurrence and overall survival. Citation Format: Pagani O, Regan MM, Fleming GF, Walley BA, Colleoni M, Láng I, Gomez HL, Tondini C, Burstein HJ, Goetz MP, Ciruelos EM, Stearns V, Debled M, Martino S, Geyer Jr CE, Pinotti G, Coates AS, Goldhirsch A, Gelber RD, Francis PA. Randomized comparison of adjuvant aromatase inhibitor exemestane (E) plus ovarian function suppression (OFS) vs tamoxifen (T) plus OFS in premenopausal women with hormone receptor positive (HR+) early breast cancer (BC): Update of the combined TEXT and SOFT trials [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS4-02.