Male BC is usually ER, PR and AR-positive, Luminal B-like/HER2-negative. Of note, 56% patients had T1 tumors but only 4% had BCS. ER was highly positive in >90% of cases but only 77% received adjuvant ET. ER, PR and AR were associated with OS and RFS, whereas grade, Ki67 and IHC surrogates were not. Significant improvement in survival over time was observed.

Background The MINDACT trial showed excellent 5-year distant metastasis-free survival of 94•7% (95% CI 92•5-96•2) in patients with breast cancer of high clinical and low genomic risk who did not receive chemotherapy. We present long-term follow-up results together with an exploratory analysis by age.Methods MINDACT was a multicentre, randomised, phase 3 trial done in 112 academic and community hospitals in nine European countries. Patients aged 18-70 years, with histologically confirmed primary invasive breast cancer (stage T1, T2, or operable T3) with up to three positive lymph nodes, no distant metastases, and a WHO performance status of 0-1 were enrolled and their genomic risk (using the MammaPrint 70-gene signature) and clinical risk (using a modified version of Adjuvant! Online) were determined. Patients with low clinical and low genomic risk results did not receive chemotherapy, and patients with high clinical and high genomic risk did receive chemotherapy (mostly anthracycline-based or taxane-based, or a combination thereof). Patients with discordant risk results (ie, patients with high clinical risk but low genomic risk, and those with low clinical risk but high genomic risk) were randomly assigned (1:1) to receive chemotherapy or not based on either the clinical risk or the genomic risk. Randomisation was done centrally and used a minimisation technique that was stratified by institution, risk group, and clinicalpathological characteristics. Treatment allocation was not masked. The primary endpoint was to test whether the distant metastasis-free survival rate at 5 years in patients with high clinical risk and low genomic risk not receiving chemotherapy had a lower boundary of the 95% CI above the predefined non-inferiority boundary of 92%. In the primary test population of patients with high clinical risk and low genomic risk who adhered to the treatment allocation of no chemotherapy and had no change in risk post-enrolment. Here, we present updated follow-up as well as an exploratory analysis of a potential age effect (≤50 years vs >50 years) and an analysis by nodal status for patients with hormone receptor-positive and HER2-negative disease. These analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT00433589, and the European Clinical Trials database, EudraCT2005-002625-31. Recruitment is complete and further long-term follow-up is ongoing.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. PURPOSE The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.

506 Background: The 70-gene signature MammaPrint has been shown to identify breast cancer patients for whom adjuvant chemotherapy (CT) could be safely omitted even in the presence of unfavorable standard clinical-pathological criteria. The MINDACT primary endpoint at 5 years median follow-up was met in 2016 (Cardoso et al, NEJM 2016) with a distant metastasis free survival (DMFS) rate at 5 years of 94.7% (95% CI: 92.5-96.2) in clinical high (C-High) / genomic low (G-Low) risk patients who received no CT. Longer follow-up is now available. Methods: 6693 patients were enrolled in the prospective phase III randomized MINDACT study (EORTC 10041/BIG3-04) between 2007-2011. We assessed the DMFS rate at 5 years in the primary test (PT) population of C-High / G-Low patients who were randomized to receive no CT (n = 644). As secondary analysis, we evaluated DMFS and overall survival (OS) in the intention to treat (ITT) population of the C-High / G-Low group randomized to CT vs no CT (n = 749 and 748 respectively). Comparisons between CT and no CT groups are low-powered. We used Kaplan-Meier estimates for time to event endpoints and hazard ratios (HR) with 95% CI from cox-regression models adjusted for stratification factors used for the randomization. Results: The median follow-up is 8.7 years, resulting in an updated 5-year DMFS rate for the PT population of C-High / G-Low patients with no CT of 95.1% (95% CI 93.1-96.6). The updated outcomes of the ITT population of C-High / G-Low patients are shown in the table. Further analyses will update the suggested age-dependent effect of CT omission for luminal breast cancer seen at 5 years in pre- versus post-menopausal women as in Tailor-X (Piccart et al, SABCS 2019). Conclusions: The primary DMFS endpoint at 5 years continues to be met in CT untreated C-High / G-Low risk women, confirming MINDACT as a positive de-escalation study. With longer follow-up and in line with the natural history of luminal breast cancer, more distant relapses do occur but the estimated gain of 2.6% for CT administration in C-High / G-Low patients remains small in light of CT harmful effects. The level IA evidence for the clinical utility of the 70-gene signature for adjuvant CT decision making is maintained. Clinical trial information: NCT00433589 . [Table: see text]

BackgroundDiscontinuation of rheumatoid arthritis (RA) treatment for lack or loss of initial response, tolerability issues, or development of antibodies against the therapeutic agent remains a challenge in clinical practice. Here we present a 6-month interim analysis of a 2-year prospective observational trial in Europe and Canada aiming to assess the real-world effectiveness, safety, and tolerability of intravenous abatacept for the treatment of moderate-to-severe RA.MethodsACTION (AbataCepT In rOutiNe clinical practice) is a prospective, observational study assessing effectiveness, safety, and tolerability of abatacept in patients with RA enrolled in Europe and Canada between May 2008 and January 2011. The patient population was divided into two groups: biologic naïve (‘first-line’) patients and patients who had previously failed treatment with at least one biologic agent (‘second-line’). Retention rates were calculated using Kaplan–Meier curve estimates. Effectiveness was measured using European League Against Rheumatism (EULAR) response criteria, the 28-item Disease Activity Score, the Clinical Disease Activity Index (CDAI), and physical function, as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). Serious adverse events (SAEs) were reported for all enrolled patients.ResultsOf 1138 consecutively enrolled patients, 1114 and 1079 patients were evaluable for retention and effectiveness, respectively. Overall, retention rates were 88.6% (95% confidence interval [CI]: 86.4, 90.4); 67.4% of patients achieved good/moderate EULAR response; 32.8% had a CDAI Low Disease Activity State (LDAS); and 44.7% a HAQ-DI response. Retention rates among first- and second-line patients were 93.0% (95% CI: 85.9, 96.6) and 88.1% (95% CI: 85.7, 90.0), respectively. The percentage of patients achieving CDAI LDAS was 40.0% (95% CI: 26.4, 53.6) for first- and 32.2% (95% CI: 28.4, 36.0) for second-line patients and the proportion achieving a HAQ-DI response was 60.3% (95% CI: 47.8, 72.9) versus 43.1% (95% CI: 39.0, 47.2), respectively. The incidence of SAEs was 4.7%.ConclusionsEvidence from this 6-month interim analysis suggests that abatacept offers an effective and well-tolerated treatment option for patients with RA, including those who have previously failed anti-tumor necrosis factor treatment. In addition, higher retention rates and effectiveness outcomes were observed when abatacept treatment was initiated earlier in the course of the disease.

ObjectiveTo assess the efficacy and safety of abatacept in biological-naive patients with rheumatoid arthritis and an inadequate response to methotrexate treated in the long-term extension (LTE) of the ATTEST trial.MethodsPatients randomly assigned to abatacept, placebo or infliximab completing the 1-year double-blind period were eligible to receive abatacept ∼10 mg/kg in the open-label LTE. Efficacy to year 2 is presented for patients randomly assigned to abatacept or infliximab who switched to open-label abatacept. Safety data are presented for all patients entering LTE regardless of double-blind treatment.ResultsOf 431 patients randomly assigned, 79.8% remained on abatacept at year 2. At years 1 and 2, 19.7% and 26.1% of abatacept and 13.3% and 28.6% of infliximab-to-abatacept patients achieved disease activity score 28-defined remission (<2.6). Safety with abatacept during the cumulative study period was consistent with the double-blind experience, with no increase in adverse event incidence following the switch to abatacept.ConclusionIn methotrexate-inadequate responders, abatacept efficacy was maintained over 2 years. For infliximab-to-abatacept patients, efficacy improvements were seen in year 2 after patients switched to abatacept. Switching directly from infliximab to abatacept was well tolerated. These data demonstrate that abatacept provides sustained responses and consistent safety, suggesting that switching from infliximab to abatacept is a viable treatment option.

Background: Sentinel node biopsy (SNB) is standard in assessing axillary lymph node status in patients with clinically node-negative breast cancer. The 5-year analysis of AMAROS trial showed that if locoregional treatment is advised after a tumor-positive axillary SNB, axillary radiotherapy (ART) is a reasonable alternative for an axillary lymph node dissection (ALND) with less side effects, though follow up was relatively short. Here we present the 10-year follow up data. Methods: From February 2001 to April 2010, patients with primary breast cancer stage cT1-2N0M0 were enrolled in the EORTC phase III non-inferiority AMAROS trial by 34 European sites. Patients were randomized between ALND and ART in case of a tumor-positive SNB. The primary endpoint, axillary recurrence rate (AxR) is now assessed at 10 years in the ITT population using Fine and Gray cumulative incidence method with deaths as competing risks, as well as secondary endpoints: overall survival (OS), distant metastasis free survival (DMFS), second primaries (including cancers other than breast cancers and contralateral DCIS) and locoregional recurrences (LRR). Little extra information beyond 5 years was available concerning Quality of Life and morbidity. Data collection is still ongoing and will be presented later. Results:Of the 4806 patients entered, 1425 patients had a tumor-positive SNB: 744 in the ALND-arm and 681 in the ART-arm, 60% with a macrometastasis. Both treatment-arms achieved a median 10-year follow-up and were comparable regarding age, tumor size, grade, tumor type and adjuvant systemic treatment. In the group who had ALND, the 5-year AxR was 0.41% (95%CI: 0.00;0.88) (4/744) and the 10-year AxR was 0.93% (95%CI:0.18;1.68) (7/744). In the group who had ART, the 5-year AxR was 1.04% (95%CI: 0.27;1.81) (7/681) and the 10-year AxR was 1.82% (95%CI: 0.74;2.94) (11/681) (HR 1.71, 95%CI: 0.67;4.39, p = 0.37). Sensitivity analysis, considering deaths and distant recurrences as competing risks, revealed consistent results. There were no significant differences between treatment arms regarding OS (ALND: 84.6% (95%CI: 81.5;87.1), ART: 81.4% (95%CI: 77.9;84.4), HR 1.17, 95%CI: 0.89;1.52, p= 0.26) and DMFS (ALND: 81.7% (95%CI: 78.5;84.4), ART: 78.2% (95%CI: 74.6;81.3), HR 1.18, 95%CI: 0.92;1.50, p=0.19). Cumulative incidence estimates of 10-year LRR are 3.59% (95%CI: 2.12;5.06) (ALND) versus 4.07% (95%CI: 2.49;5.65) (ART) (p= 0.69). More second primaries were observed after ART: 75/681 (21 contralateral breast) as compared to ALND: 57/744 (11 contralateral breast) (p = 0.035). All results are consistent in the per protocol analysis of patients with a tumor-positive SNB. Conclusion: Axillary recurrence after 10 years in patients with a tumor-positive SNB who were treated with ART is extremely rare and not significantly different from patients who were treated with ALND. OS, DMFS and locoregional control are also comparable. Second primaries including contralateral breast cancers are more frequently encountered after ART, but the difference is still low in absolute numbers. Thus, ART is a safe treatment for breast cancer patients with a tumor-positive SNB. Citation Format: Rutgers EJ, Donker M, Poncet C, Straver ME, Meijnen P, van de Velde CJ, Mansel RE, Blanken C, Orzalesi L, Klinkenbijl JH, van der Mijle HC, Veltkamp SC, van 't Riet M, Albregts M, Marinelli A, Rijna H, Tobon Morales R, Snoj M, Bundred N, Chauvet MP, Merkus JW, Petignat P, Schinagl DA, Coens C, Peric A, Bogaerts J, van Tienhoven G. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023) [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 GS4-01.

IntroductionThe goal of this study was to compare the efficacy in terms of Health Assessment Questionnaire change from baseline (HAQ CFB), 50% improvement in American College of Rheumatology criterion (ACR-50) and Disease Activity Score in 28 joints (DAS28) defined remission (< 2.6) between abatacept and other biologic disease modifying anti-rheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA) who have inadequate response to methotrexate (MTX-IR).MethodsA systematic literature review identified controlled trials investigating the efficacy of abatacept (three studies), etanercept (two studies), infliximab (two), adalimumab (two), certolizumab pegol (two) ritixumab (three), and tocilizumab (two) in MTX-IR patients with RA. The clinical trials included in this analysis were similar with respect to trial design, baseline patient characteristics and background therapy (MTX). The key clinical endpoints of interest were HAQ CFB, ACR-50 and DAS28 < 2.6 measured at 24 and 52 weeks. The results were analysed using network meta-analysis methods that enabled calculation of an estimate for expected relative effect of comparative treatments. Analysis results were expressed as the difference in HAQ CFB score and odds ratio (OR) of achieving an ACR-50 and DAS28 response and associated 95% credible intervals (CrI).ResultsThe analysis of HAQ CFB at 24 weeks and 52 weeks showed that abatacept in combination with MTX is expected to be more efficacious than MTX monotherapy and is expected to show a comparable efficacy relative to other biologic DMARDs in combination with MTX. Further, abatacept showed comparable ACR-50 and DAS28 < 2.6 response rates with other biologic DMARDs at 24 and 52 weeks, except for ACR-50 compared to certolizumab pegol at 52 weeks and for DAS28 < 2.6 compared to tocilizumab at 24 weeks. Sensitivity analyses confirmed the robustness of the findings.ConclusionsAbatacept in combination with MTX is expected to result in a comparable change from baseline in HAQ score and comparable ACR-50 and DAS28 < 2.6 response rates in MTX-IR patients compared to other approved biologic agents.