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  • 1
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    Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2– Early Breast Cancer
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 23 ( 2022-08-10), p. 2557-2567
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 23 ( 2022-08-10), p. 2557-2567
    Abstract: To our knowledge, WSG-ADAPT-HR+/HER2– (ClinicalTrials.gov identifier: NCT01779206 ; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer. MATERIALS AND METHODS Baseline and postendocrine Ki67 (Ki67 post ) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67 post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental ( v control) arm; secondary end points included distant DFS, overall survival, and translational research. RESULTS Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was –3.3%, establishing prespecified noninferiority ( P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age 〉 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% ( P 〈 .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS 〉 25 (n = 4,203, P 〈 .001). CONCLUSION WSG-ADAPT-HR+/HER2– demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.21.02759
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 2
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    Adjuvant dynamic marker-adjusted personalized therapy comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2- early breast cancer: ADAPTcycle.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS609-TPS609
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. TPS609-TPS609
    Abstract: TPS609 Background: The WSG ADAPT trial program focusses on individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. Clinical feasibility of the WSG ADAPT trial goals - early response assessment and subtype-specific therapy tailoring to those patients (pts) who are most likely to benefit - has recently been confirmed by the 5-years survival data of the ADAPT HR+/HER2- clinical trial. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, (neo)adjuvant, non-blinded, randomized, controlled phase III trial (NCT04055493) investigating whether treatment with the CDK4/6 inhibitor ribociclib (600mg/day) together with ET is superior to standard-chemotherapy (CT) in intermediate-risk HR+/HER2- EBC. Definition of intermediate-risk is either based on Oncotype DX and endocrine responder status (measured by Ki67-response after 2-4 weeks of induction endocrine therapy (ET)) or on low-intermediate baseline Ki67 and high estrogen receptor (ER)/progesterone receptor (PR)-expression (Dowsett et al. NPJ Breast Cancer 2020). Co-primary endpoints are DFS and dDFS. It is planned to screen 5600 pts and to randomize 1670 pts (1002 to ribociclib + ET; 668 to standard CT followed by ET). Study start was in July 2019 (88 sites, enrollment period 42 months) and until date of submission, 3079 pts have been screened and 811 randomized (490 ribociclib / 321 CT). Pre-/postmenopausal pts with histologically confirmed invasive HR+/HER2- EBC with high clinical risk (cT2-4 or Ki-67 20% or G3 or cN+) are eligible if they fulfil the ADAPT intermediate-risk criteria: Recurrence Score (RS) ≤25 plus several risk factors and poor ET responder, RS 〉 25 and ET-responder in p/cN0-1 pts, or RS ≤25 with c/pN2-3 in ET-responder. Direct randomization of premenopausal patients (irrespective of ET-response) with c/pN0 and RS 16-25 or c/pN1 with RS 0-25 is allowed according to investigator´s decision; however, based on the ADAPT results, ET+ovarian function suppression alone is strongly recommended in ET-responders. Treatment duration is 2 years for the ribociclib + aromatase inhibitor (AI) (premenopausal: AI + GnRH)-arm and 16-24 weeks for the CT-arm; neoadjuvant or adjuvant treatment is allowed. The minimum 5-year follow-up phase includes standard adjuvant ET. ePROs are collected using CANKADO; ECG monitoring is performed using a novel eHealth method. Translational analyses: Tumor tissue will be collected prior to ET, after at least 3 weeks of ET, if residual tumor is diagnosed (neoadjuvant treatment), and at recurrence, to identify potential resistance markers. Exploratory tissue biomarker research will be conducted to assess alterations in molecular markers. In addition, ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression relevant for HR+/HER2- EBC. Clinical trial information: NCT04055493.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.TPS609
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
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    Gene expression signatures, stromal tumor infiltrating lymphocytes (sTILs), and change in tumor cellularity to predict pathological complete response (pCR) after 12 week de-escalated neoadjuvant endocrine therapy (ET) vs paclitaxel + dual HER2 blockade in the WSG-TP-II trial.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 519-519
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 519-519
    Abstract: 519 Background: There are limited data on predictive biomarkers for de-escalated ET or chemotherapy with dual anti-HER2 blockade in HR+/HER2+ early breast cancer (BC). In this translational pre-planned project of the WSG-TP-II phase II-trial (NCT03272477), we aimed to identify associations of gene expression signatures and sTILs with pCR. Methods: Patients with cT1c-cT4c, cN0-3 centrally confirmed HR+/HER2+ BC were randomized to 12 weeks of standard ET (n = 100) or paclitaxel (Pac; n = 107). All patients received trastuzumab + pertuzumab (T+P) q3w as neoadjuvant and adjuvant treatment. Gene expression signatures were analyzed using NanoString BC360 panel in baseline biopsies (T+P+ET: n = 72; T+P+Pac: n = 78). sTILs were analyzed in 93 (T+P+ET) and 97 patients (T+P+Pac) at baseline and in 65 (T+P+ET) and 57 patients (T+P+Pac) at week 3. Impacts of standardized BC360 gene expression signatures and sTILs on pCR (ypT0/is ypN0; primary endpoint) expressed in odds ratios (OR) were estimated by logistic regression analysis. Results: pCR rate in patients with BC360 analysis was 39.3% (T+P+ET: 23.6%; T+P+Pac: 53.9%). Overall, ERBB2 (OR 2.37; 95%CI 1.55, 3.62) and cytotoxic cells signature (OR 1.42; 95%CI 1.02, 1.99) were favorable for pCR, while apoptosis (OR 0.64; 95%CI 0.44, 0.92), estrogen receptor 1 (OR 0.60; 95%CI 0.42, 0.85), estrogen receptor signaling (OR 0.64; 95%CI 0.45, 0.91), and progesterone receptor (OR 0.67; 95%CI 0.47, 0.94) signatures were unfavorable. Analyzing by treatment arm, a similar pattern was observed in the T+P+Pac arm (ERBB2: OR 2.01; apoptosis: OR 0.59; estrogen- and progesterone-related signatures: OR 0.41-0.58), but not in the T+P+ET arm where only ERBB2 was prognostic for pCR (OR 7.24; 95%CI 2.12, 24.05). Baseline ≥30% sTIL levels (vs 〈 30% sTILs; n = 16 vs n = 174) were associated with pCR (OR 5.16; 95%CI 1.60, 16.66); significance was not achieved in either trial arm. Compared to 〈 30% sTILs (n = 90), low tumor cellularity at week 3 precluding sTILs analysis ( 〈 500 invasive tumor cells, n = 22), but not ≥30% sTILs (n = 10), was prognostic for pCR in all patients (OR 9.47; 95%CI 2.94, 30.50) and in individual trial arms (OR 6.00-11.79). Conclusions: This hypothesis-generating translational results suggest that gene expression signatures (particularly ERBB2), baseline sTILs, and low tumor cellularity at week 3 predict pCR after ET + double HER2 blockade. Future neoadjuvant trials are needed to prospectively test the use of baseline gene expression and sTILs analysis, and early on-treatment cellularity measurement to select patients with HR+/HER2+ tumors for de-escalated endocrine-therapy-based approaches. Clinical trial information: NCT03272477 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.519
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 4
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    Abstract GS4-04: Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score 〈26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-04-GS4-04
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. GS4-04-GS4-04
    Abstract: Background: In HR+/HER2- N0 early breast cancer (EBC), patients (pts) with Recurrence Score™ (RS) & lt;26 (postmenopausal) and & lt;16 (premenopausal) have excellent prognosis and do not benefit fromadditional chemotherapy. However, prognostic impact of RS in N+ disease and importance of Ki67response after short preoperative endocrine therapy (ET) in the context of genomic signatures remainunclear. For the first time, we present survival results from the large prospective phase III WSG-ADAPTHR+/HER- trial combining both static (RS in baseline core biopsy) and dynamic (Ki67 response)biomarkers to optimize adjuvant therapy in luminal EBC. Methods: 5625 pts were registered and 4691 finally treated by ET (n=2356) or CT (n=2335) within ADAPTHR+/HER2-. ET-trial ITT population comprised 2290 pts: n=868 RS0-11, n=1422 RS12-25/ET-response(30% premenopausal, 26% N1). 5y-iDFS was 93.9% (95%-CI: [91.8% to 95.4%]) in RS0-11 and 92.6%(95%-CI: [90.8% to 94.0%] ) in RS12-25/ET-responders. Since the one-sided upper 95% confidence limitof the 5y-iDFS difference was 3.3%, the pre-specified criterion to accept the primary NI-hypothesis wasmet (p=.05).5y-dDFS was 96.3% [94.6% to 97.5%] vs. 95.6% [94.2% to 96.7%] ) in RS0-11 vs. RS12-25/ET-responders,respectively (95%-CI for 5y-dDFS difference: [-1.2% to 2.6%]). 5y-OS was also excellent and similar(98.0% [96.7% to 98.9%] vs. 97.3% [96.1 to 98.1%]) in RS0-11 vs. RS12-25/ET-responders, respectively(95% CI for the 5y-OS difference: [-0.7% to 2.2%] ). Results: 5625 pts were registered and 4691 finally treated by ET (n=2356) or CT (n=2335) within ADAPTHR+/HER2-. ET-trial ITT population comprised 2290 pts: n=868 RS0-11, n=1422 RS12-25/ET-response(30% premenopausal, 26% N1). 5y-iDFS was 93.9% (95%-CI: [91.8% to 95.4%]) in RS0-11 and 92.6%(95%-CI: [90.8% to 94.0%] ) in RS12-25/ET-responders. Since the one-sided upper 95% confidence limit of the 5y-iDFS difference was 3.3%, the pre-specified criterion to accept the primary NI-hypothesis was met (p=.05) 5y-dDFS was 96.3% [94.6% to 97.5%] vs. 95.6% [94.2% to 96.7%] ) in RS0-11 vs. RS12-25/ET-responders, respectively (95%-CI for 5y-dDFS difference: [-1.2% to 2.6%]). 5y-OS was also excellent and similar (98.0% [96.7% to 98.9%] vs. 97.3% [96.1 to 98.1%]) in RS0-11 vs. RS12-25/ET-responders, respectively (95% CI for the 5y-OS difference: [-0.7% to 2.2%] ). Conclusions: In pN0-1 luminal EBC pts receiving ET alone, pts with RS12-25/ET-response had 5y-iDFSwell above 90% and very close to RS0-11 pts. Both groups had excellent similar dDFS and OS. DynamicET response thus complements RS as a key selection criterion for omission of chemotherapy in pN0-1HR+/HER2- EBC. Citation Format: Nadia Harbeck, Oleg Gluz, Sherko Kuemmel, Matthias Christgen, Michael Braun, Bahriye Aktas, Kerstin Luedtke-Heckenkamp, Helmut Forstbauer, Eva-Maria Grischke, Claudia Schumacher, Maren Darsow, Katja Krauss, Benno Nuding, Marc Thill, Jochem Potenberg, Christoph Uleer, Mathias Warm, Hans H. Fischer, Wolfram Malter, Michael Hauptmann, Ronald Kates, Monika Graeser, Rachel Wuerstlein, Steve Shak, Rick Baehner, Hans Kreipe, Ulrike Nitz, West German Study Group. Endocrine therapy alone in patients with intermediate or high-risk luminal early breast cancer (0-3 lymph nodes), Recurrence Score & lt;26 and Ki67 response after preoperative endocrine therapy: Primary outcome results from the WSG-ADAPT HR+/HER2- trial [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 GS4-04.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-GS4-04
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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  • 5
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    Abstract P2-13-03: KEYRICHED-1 - A prospective, multicenter, open label, neoadjuvant phase II single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype
    American Association for Cancer Research (AACR) ; 2022
    In:  Cancer Research Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-13-03-P2-13-03
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. P2-13-03-P2-13-03
    Abstract: Background: De-escalating strategies seem promising inHER2-positive early breast cancer (EBC) and chemo-free regimens are thus of keyinterest. Recent data have underlined the role of tumor immunogenicity inresponse to de-escalated neoadjuvant anti-HER2 therapy. Therefore, theprospective single arm hypothesis-generating phase II KEYRICHED-1 trial (NCT03988036)investigates the pCR rate in patients with HER2-enriched EBC receiving fourcycles of the dual anti-HER2 blockade in combination with the checkpointinhibitor pembrolizumab. Initial studies with dual antibody-based HER2 blockadealone were able to achieve pCR-rates of 20-40%, which did not quite match the pCRrates obtained with concurrent chemotherapy. KEYRICHED-1 aims at achieving pCR-ratescomparable to standard chemotherapy-containing regimens by incorporating appropriatemolecular selection and immune oncology. Methods: A total of 48 pre- and postmenopausal patients with newly diagnosed HER22+ or 3+ EBC (stage I-III) and HER2-enriched (HER2-E) subtype by PAM50 wereenrolled in this single-arm study. All patients received four cycles of studytreatment with pembrolizumab (200mg), trastuzumab biosimilar (Trazimera®,loading dose 8mg/kg bodyweight (BW), maintenance dose 6mg/kg BW), and pertuzumab(loading dose 840mg/kg BW, maintenance dose 420mg/kg BW) q21d . Primaryendpoint was centrally confirmed pCR (ypT0/is, ypN0). The trial was planned asa Simon's two-Stage design (null and alternative pCR were 40% and 60%); interimanalysis after 16 patients had to show a pCR rate of at least 50% to continuerecruitment. Results: Between 05/2020 and 03/2021, 98 patients werescreened. N=52 (55%) had HER2-E subtype,of whom 48 patients entered thetreatment phase. Median patient age was 57 years (28-83). 65% had tumors & gt; 2cm and 30% positive lymph node status. Centrally confirmed pCR rate in surgicalspecimens was 46% (95% CI 0.31-0.62) in the 43 patients of the per protocolpopulation, and 52% (95%CI 0.37-0.67) in all 46 evaluable patients (localassessment; two pCRs verified only by core biopsy) (p=0.22 and p=0.06 for nullhypothesis, respectively). Despite HER2-E subtype, no pCR was observed in the 4patients with immunohistochemical (IHC) HER2 2+/ISH-positive status in contrastto 20/39 (51.2%) pCRs in IHC HER2 3+ tumors. Centrally confirmed pCR rate in HR+/HER2+tumors was38.5% compared to 58.5% in HR-/HER2+ tumors. No new safety signals wereobserved. Conclusions: These are the first results of a neoadjuvant chemotherapy-free12-week de-escalation anti-HER2-regimen with trastuzumab and pertuzumab incombination with the PD-1 inhibitor pembrolizumab in patients with a HER2-E EBC.In the context of the WSG ADAPT HER2+ de-escalation trials the observed pCRrates compare favourably in HR+ as well as HR- HER2 EBC. Moreover, KEYRICHED-1demonstrates that with appropriate molecular patient selection clinicallymeaningful pCR rates in the range of those obtained with longer, more toxicchemotherapy-containing regimens can be achieved. Citation Format: Sherko Kuemmel, Oleg Gluz, Mattea Reinisch, Athina Kostara, Iris Scheffen, Monika Graeser, Kerstin Luedtke-Heckenkamp, Andreas Hartkopf, Felix Hilpert, Angela Kentsch, Carsten Ziske, Reinhard Depenbusch, Michael Braun, Jens Blohmer, Christine zu Eulenburg, Matthias Christgen, Stephan Bartels, Hans Kreipe, Enrico Pelz, Peter Schmid, Nadia Harbeck. KEYRICHED-1 - A prospective, multicenter, open label, neoadjuvant phase II single arm study with pembrolizumab in combination with dual anti-HER2 blockade with trastuzumab and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS21-P2-13-03
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 6
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    Abstract P3-01-09: Maintenance Therapy with ET and Ribociclib after 1st line Chemotherapy (CT) in Hormone Receptor (HR)-positive/HER2-negative Metastatic Breast Cancer (BC): a Phase II Trial (AMICA)
    American Association for Cancer Research (AACR) ; 2023
    In:  Cancer Research Vol. 83, No. 5_Supplement ( 2023-03-01), p. P3-01-09-P3-01-09
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 5_Supplement ( 2023-03-01), p. P3-01-09-P3-01-09
    Abstract: Background: Approximately one third of HR-positive, metastatic BC patients receive CT as initial treatment. Longer duration of CT is associated with a better long-term outcome. However, the duration of CT is usually limited by toxicities and patients and physicians´ preferences, resulting in treatment duration & lt; 6 months. Replacing CT by maintenance endocrine treatment is an accepted treatment strategy in everyday clinical practice, but prospective data are lacking. Well tolerated maintenance treatments with the potential to prolong progression-free survival (PFS) and even overall survival (OS) are urgently needed. Methods: The AMICA trial (NCT03555877) is a multicenter, prospective, open-label phase II study to test the addition of the CDK4/6 inhibitor ribociclib to ET as maintenance therapy in patients with disease control after at least 4 cycles of 1st line mono- or poly-CT at investigator´s discretion. Initially patients were randomized to receive ET +/- ribociclib. Due to slow accrual the study was amended after inclusion of 37 patients and all subsequent patients received ET+ribociclib. Treatment was given until disease progression, unacceptable toxicity, or withdrawal of consent. Maintenance ET could have already been started up to 6 weeks before enrolment. One previous line of ET including prior use of CDK4/6 inhibitor was allowed. The primary objective was to estimate the median PFS of patients treated with ET+ribociclib. Secondary objectives were median OS, safety, compliance, clinical benefit rate (CBR) and patient reported outcomes. The trial was closed prematurely due to slow recruitment. Results: Between March 2018 and December 2021, 56 patients were enrolled and started treatment (n=44 received ET+ribociclib, 12 ET alone). Median age of patients treated with ET+ribociclib was 60 years, 52.3% were overweight/obese, 88.6% were postmenopausal at study entry, 39.5% were M1 at primary diagnosis. Overall, 46.5% of the patients received letrozole, 14% anastrozole, 7.0% exemestane, 32.6% fulvestrant. A total of 10 (22.7%) patients in the ET+ribociclib arm had at least one serious adverse event, 2 at least one adverse event of special interest (N=1 hepatotoxicity, N=1 overdose). Conclusions: Results on the primary and secondary objectives will be presented at the meeting. Citation Format: Thomas Decker, Kerstin Lüdtke-Heckenkamp, Luidmila Melnichuk, Jenny Furlanetto, Kristina Lübbe, Mark-Oliver Zahn, Marcus Schmidt, Carsten Denkert, Ralf Lorenz, Volkmar Müller, Dirk-Michael Zahm, Christoph Mundhenke, Stefan Bauer, Marc Thill, Peter Seropian, Natalie Filmann, Sibylle Loibl. Maintenance Therapy with ET and Ribociclib after 1st line Chemotherapy (CT) in Hormone Receptor (HR)-positive/HER2-negative Metastatic Breast Cancer (BC): a Phase II Trial (AMICA) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-01-09.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS22-P3-01-09
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 7
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    Abstract PS10-16: Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study
    American Association for Cancer Research (AACR) ; 2021
    In:  Cancer Research Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS10-16-PS10-16
    Details
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 81, No. 4_Supplement ( 2021-02-15), p. PS10-16-PS10-16
    Abstract: Background: In MONALEESA-3 and MONALEESA-7 trials, ribociclib (RIB, a selective CDK4/6 inhibitor) in combination with endocrine therapy (aromatase inhibitor [AI] or fulvestrant [FUL] ) demonstrated a significant prolongation of overall survival among patients with breast cancer (BC), regardless of menopausal status and treatment-line. In the premenopausal or perimenopausal women, RIB + AI/FUL should be combined with a luteinizing hormone-releasing hormone agonist. The real-world evidence for the effectiveness, safety, and tolerability of RIB + AI/FUL in the routine clinical practice is needed to support the use of this combination. Methods: RIBANNA is a prospective, non-interventional study ongoing in Germany since October 2017. Pre-, peri- and postmenopausal women (planned, n = 3020) treated with RIB + AI/FUL, or endocrine monotherapy (ET), or chemotherapy (CT) as the first-line treatment for HR+/HER2- aBC in accordance with German guidelines were included. Data from routine clinical practice in all 3 cohorts, including further lines of sequential therapy, were collected. Updated data on baseline demographics and safety analysis will be presented. Additionally, first experience with CANKADO, an innovative digital and patient-friendly application for electrocardiogram (ECG) measurement, are described. By combining this app to Kardia mobile (AliveCor’s single lead device), single-lead ECG can be recorded and sent via the CANKADO app for a cardiologist to read over. The cardiologist reviews the measurements, and reports the corrected QT interval by Fredericia (QTcF) results towards the trial site. Impact of the use of CANKADO onto the clinical routine will be analyzed. Results: For the second interim analysis, 1141 patients were enrolled until July 12th, 2019, while the full analysis set comprised 813 patients (Table 1). Median duration of RIB exposure in patients on RIB + AI/FUL vs total population was 151 vs 150 days respectively. At cut-off date, patients received first-line (89%, n = 1016), second-line (7%, n = 82), and third-line treatments (1%, n = 11). A starting dose of 600 mg per day for RIB in the first-line setting was seen in most of the patients (85%); data of second-line patients will be reported later. The first-line mean daily dose of RIB was 451.6 mg/day RIB was prescribed mainly in combination with letrozole (75%), fulvestrant (12%), anastrozole (7%), and exemestane (6%). A total of 62% of patients in the study were documented as therapy-naïve for ET. Of 424 patients with early breast cancer, 129 (30%) had documented prior CT without ET. The most common all-grade adverse events frequently noted in RIB + AI/FUL cohort in comparison with other cohorts were nausea (RIB [19%] vs ET [9%] vs CT [11%] ), neutropenia (19% vs 1% vs 10%), fatigue (17% vs 9% vs 14%), and leukopenia (14% vs 4% vs 12%). The usage of CANKADO application to assess QTcF was initiated in the year 2019 and first data will be presented. Conclusion: RIBANNA study showed diverse population characteristics among the patients who received RIB treatment in a real-world setting. The third interim analysis is planned in October 2020, and the updated baseline data, information on safety, digital ECG measurement using CANKADO application will be presented. Baseline Demographic Characteristics as of Second Interim AnalysisDemographic VariableRIB + AI/FUL (n = 658)Endocrine Therapy (n = 78)Chemotherapy (n = 77)Mean age, years (SD)67 (11)72 (12)62 (10)Mean time since initial diagnosis, years6.17.23.6T stage at baseline*, n (%)TX204 (31)28 (36)18 (23)T0+T1132 (20)12 (15)11 (14)T2-T4302 (46)35 (45)42 (54)N stage at baseline*, n (%)NX212 (32)29 (37)28 (36)N0+N1317 (48)36 (46)35 (46)N2+N3108 (16)10 (13)8 (10)M stage at baseline*, n (%)MX6 (1)0 (0)0 (0)M018 (3)1 (1)1 (1)M1616 (94)75 (96)71 (92)Metastatic location at baseline*, n (%)CNS, liver, lungs258 (39)14 (18)42 (54)Bone only181 (28)42 (54)11 (14)Skin, lymph nodes, other149 (23)16 (20)14 (18)*Remaining cases are missing.CNS, central nervous system. Citation Format: Achim Wöckel, Cosima Brucker, Thomas Decker, Jörg Falbrede, Helmut Forstbauer, Thomas Göhler, Oliver Hoffmann, Christian Jackisch, Jan Janssen, Andreas Köhler, Kerstin Lüdtke-Heckenkamp, Diana Lüftner, Frederik Marmé, Arnd Nusch, Toralf Reimer, Christian Roos, Marcus Schmidt, Rudolf Weide, Peter Fasching. Real-world efficacy of ribociclib + aromatase inhibitor/fulvestrant, or endocrine monotherapy, or chemotherapy as first-line treatment in women with HR-positive, HER2-negative locally advanced or metastatic breast cancer: Third interim analysis from the RIBANNA study [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 PS10-16.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    URL: Article
    DOI: 10.1158/1538-7445.SABCS20-PS10-16
    RVK:
    XA 36000
    RVK:
    XA 10000
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2021
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    Cetuximab, docetaxel, and cisplatin versus platinum, fluorouracil, and cetuximab as first-line treatment in patients with recurrent or metastatic head and neck squamous-cell carcinoma (GORTEC 2014-01 TPExtreme): a multicentre, open-label, randomised, phase 2 trial
    Elsevier BV ; 2021
    In:  The Lancet Oncology Vol. 22, No. 4 ( 2021-04), p. 463-475
    Details
    In: The Lancet Oncology, Elsevier BV, Vol. 22, No. 4 ( 2021-04), p. 463-475
    Type of Medium: Online Resource
    ISSN: 1470-2045
    URL: Article
    DOI: 10.1016/S1470-2045(20)30755-5
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2049730-1
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    Fractalkine Is an Epithelial and Endothelial Cell-Derived Chemoattractant for Intraepithelial Lymphocytes in the Small Intestinal Mucosa
    The American Association of Immunologists ; 2000
    In:  The Journal of Immunology Vol. 164, No. 6 ( 2000-03-15), p. 3368-3376
    Details
    In: The Journal of Immunology, The American Association of Immunologists, Vol. 164, No. 6 ( 2000-03-15), p. 3368-3376
    Abstract: Fractalkine is a unique chemokine that combines properties of both chemoattractants and adhesion molecules. Fractalkine mRNA expression has been observed in the intestine. However, the role of fractalkine in the healthy intestine and during inflammatory mucosal responses is not known. Studies were undertaken to determine the expression and function of fractalkine and the fractalkine receptor CX3CR1 in the human small intestinal mucosa. We identified intestinal epithelial cells as a novel source of fractalkine. The basal expression of fractalkine mRNA and protein in the intestinal epithelial cell line T-84 was under the control of the inflammatory mediator IL-1β. Fractalkine was shed from intestinal epithelial cell surface upon stimulation with IL-1β. Fractalkine localized with caveolin-1 in detergent-insoluble glycolipid-enriched membrane microdomains in T-84 cells. Cellular distribution of fractalkine was regulated during polarization of T-84 cells. A subpopulation of isolated human intestinal intraepithelial lymphocytes expressed the fractalkine receptor CX3CR1 and migrated specifically along fractalkine gradients after activation with IL-2. Immunohistochemistry demonstrated fractalkine expression in intestinal epithelial cells and endothelial cells in normal small intestine and in active Crohn’s disease mucosa. Furthermore, fractalkine mRNA expression was significantly up-regulated in the intestine during active Crohn’s disease. This study demonstrates that fractalkine-CX3CR1-mediated mechanism may direct lymphocyte chemoattraction and adhesion within the healthy and diseased human small intestinal mucosa.
    Type of Medium: Online Resource
    ISSN: 0022-1767 , 1550-6606
    URL: Article
    DOI: 10.4049/jimmunol.164.6.3368
    RVK:
    XA 54100
    RVK:
    XA 10000
    Language: English
    Publisher: The American Association of Immunologists
    Publication Date: 2000
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  • 10
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    Real-world efficacy of ribociclib (RIB) plus aromatase inhibitor (AI)/fulvestrant (FUL), or endocrine monotherapy (ET), or chemotherapy (CT) as first-line (1L) treatment (tx) in patients (pts) with hormone receptor–positive (HR+), human epidermal growth factor receptor-2–negative (HER2–) advanced breast cancer (ABC): Results of fourth interim analysis (IA) from RIBANNA.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 1065-1065
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 1065-1065
    Abstract: 1065 Background: RIBANNA is a real-world, noninterventional study conducted in Germany evaluating efficacy, safety, and tolerability of RIB in combination with AI/FUL aiming to gain insights into routine clinical practice for pts with HR+, HER2– ABC. Here, we present results of the fourth IA from RIBANNA. Methods: Pre-, peri- and postmenopausal pts who received 1L tx with RIB+AI/FUL, or ET or CT for HR+, HER2– ABC were included in accordance with the German tx guideline. The effect of baseline demographic characteristics, including histological grade, age, previous adjuvant tx, Eastern Cooperative Oncology Group-performance score (ECOG-PS), and metastatic sites on progression-free survival was evaluated using Cox regression model. Results: At data cutoff October 11, 2021, 2598 pts were enrolled in the study (RIB+AI/FUL, n = 2177; ET, n = 239; CT, n = 182). Data from 1L tx were available for 2492 pts (95.9%), second-line tx for 689 pts (26.5%), third-line tx for 263 pts (10.1%), and fourth-line tx for 94 pts (3.6%). Significant differences were observed in baseline mean age and metastatic sites for pts in RIB+AI/FUL cohort vs ET and CT cohorts (both 〈 0.001). At baseline, the mean (SD) ages of pts were 65.5 (11.6), 70.7 (11.5) and 61.6 (11.6) years in RIB+AI/FUL, ET, and CT cohorts, respectively. While comparing the performance status, 44.2% of pts in RIB+AI/FUL, 34.7% of pts in ET and 42.1% of pts in CT cohort were fully active with ECOG-PS = 0. CNS, liver, or lung metastases were recorded in 42.6% of pts in RIB+AI/FUL, 26.8% of pts in ET and 67.1% of pts in CT cohort. Bone only metastases were reported in 30.8%, 47.9% and 15.0% of pts in RIB+AI/FUL, ET, and CT cohorts, respectively. Overall, 32.1%, 37.7%, and 52.7% of pts discontinued the study in RIB+AI/FUL, ET, and CT cohorts, respectively, the most common reasons being deaths (16.1%,17.2%, and 31.9%, respectively) and lost to follow-up (5.9%, 8.8%, and 9.3%, respectively). The most common tx-emergent adverse event (grade 3 or 4) observed in RIB+AI/FUL cohort was neutropenia (14.8%), while 6.6% and 6.9% of pts in ET and CT cohorts, respectively, experienced neutropenia. The efficacy results from all 3 cohorts, including Kaplan-Meier curves, will be presented during ASCO 2022. Conclusions: RIBANNA study showed diverse population characteristics among pts who received RIB tx in a real-world setting. Overall higher number of pts were treated in 1L with RIB+AI/FUL followed by ET and CT. The differences in baseline characteristics on metastatic pattern, age, and ECOG-PS reflect different selection strategies for 1L tx decision. No new safety signals were identified. Clinical trial information: CLEE011ADE03.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.1065
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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