Rupert Bartsch (Vienna, Austria)
Medical University of ViennaAuthor Of 5 Presentations
Clinical Case in TNBC discussion (ID 467)
75P - Interim analysis (n=150) of the multi-national, prospective, non-interventional ELEANOR study observing real-life extended adjuvant treatment with neratinib in patients with HER2+ / HR+ early breast cancer (eBC) (ID 90)
- Nadia Harbeck (Munich, Germany)
- Denise Wrobel (Bamberg, Germany)
- Matthias Zaiss (Freiburg im Breisgau, Germany)
- Dagmar Guth (Plauen, Germany)
- Andrea Distelrath (Plauen, Germany)
- Jürgen Terhaag (Eggenfelden, Germany)
- Andreas Lorenz (Hildburghausen, Germany)
- Rupert Bartsch (Vienna, Austria)
- Urs Breitenstein (Zurich, Switzerland)
- Michael Schwitter (Chur, Switzerland)
- Marija Balic (Graz, Austria)
- Christian Jackisch (Offenbach am Main, Germany)
- Volkmar Müller (Hamburg, Germany)
- Gabriel Rinnerthaler (Salzburg, Austria)
- Marcus Schmidt (Mainz, Germany)
- Khalil Zaman (Lausanne, Switzerland)
- Timo Schinköthe (Kirchheim, Germany)
- Diana Luftner (Berlin, Germany)
Abstract
Background
Neratinib is registered in Europe as extended adjuvant treatment for adult patients with Human Epidermal Growth Factor Receptor 2-positive (HER2+) and Hormone receptor-positive (HR+) eBC within one year after completed adjuvant trastuzumab-based therapy (“EMA-/Swiss-label” population). In the ExteNET trial, extended adjuvant neratinib improved the absolute 5-year invasive disease-free survival rate by 5.1% vs. placebo in this population (90.8% vs. 85.7%; HR 0.58 [95% CI 0.41-0.82]). More pronounced benefit was observed in patients with non-pCR after neoadjuvant trastuzumab-based therapy and/or in patients who completed one year of neratinib (descriptive post-hoc analyses). In the absence of primary prophylaxis, grade 3 diarrhea occurred in 39% of patients in the ExteNET trial. ELEANOR is the first study to investigate real-world use of neratinib and its management in eBC patients in Germany, Austria and Switzerland.
Methods
300 patients with HER2+/HR+ eBC will be enrolled in accordance with the specifications of the local Summary of Product Characteristics. Primary objective is the proportion of patients adherent to neratinib treatment (i.e., neratinib intake for ≥75% of treatment days). Secondary objectives include analysis of prior trastuzumab-based therapies (including pertuzumab and T-DM1), neratinib dosing and management, relapses, safety / tolerability, and health-related quality of life (using the CANKADO eHealth application).
Results
Between July 2020 and Feb 2022, 206 patients were enrolled at 59 sites; patient enrollment is ongoing. We will present results from the interim analysis on the first 150 enrolled patients who have been observed for at least 3 months (data cut Nov 2021, analyses ongoing). Baseline demographics and tumor characteristics, prior trastuzumab-based treatments, and neratinib safety and tolerability will be reported.
Conclusions
ELEANOR will help to characterize adherence to neratinib and use of extended adjuvant HER2-targeted therapy in the current treatment landscape focusing on neratinib management after different prior therapies.
Editorial acknowledgement
Editorial assistance was provided by Anna Resch, Pierre Fabre Pharma GmbH, Freiburg, Germany.
Legal entity responsible for the study
Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).
Funding
Pierre Fabre Pharma GmbH (Freiburg, Germany), Pierre Fabre Pharma Austria (Wels, Austria) and Pierre Fabre Pharma AG (Allschwil, Switzerland).
Disclosure
N. Harbeck: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Exact Sciences, Eli Lilly, Gilead, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Sandoz, Seagen, WSG; Financial Interests, Institutional, Other: clinical trials. D. Wrobel: Financial Interests, Personal, Other: Roche, Novartis. M. Zaiss: Financial Interests, Personal, Other: Celgene, AstraZeneca, RG, AKS, Vifor, Pfizer, Janssen, Novartis, AbbVie; Financial Interests, Personal and Institutional, Other: Roche, Eli Lilly; Financial Interests, Institutional, Other: GBG. R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. U. Breitenstein: Financial Interests, Institutional, Other: Novartis, Roche, AstraZeneca, Eli Lilly, Pierre Fabre, Pfizer, SAKK; Non-Financial Interests, Personal, Other: SGMO, SGS, SAKK. M. Schwitter: Financial Interests, Personal and Institutional, Other: Pierre Fabre. M. Balic: Financial Interests, Personal, Other: Amgen, Pierre Fabre, Daiichi Sankyo, Bayer, Samsung, Seagen; Financial Interests, Personal and Institutional, Other: Novartis, Eli Lilly, Pfizer, Celgene, AstraZeneca, MSD, Roche; Financial Interests, Institutional, Other: ABCSG, IBCSG, BIG. C. Jackisch: Financial Interests, Personal, Other: Roche, AstraZeneca, Eisai, Pfizer, Eli Lilly, Novartis, Exact Sciences; Non-Financial Interests, Personal, Other: Roche. V. Müller: Financial Interests, Personal, Other: Amgen, AstraZeneca, Daiichi Sankyo, Eisai, GSK, Pfizer, MSD, Medac, Novartis, Roche, Teva, Seagen, Onkowissen, high5 Oncology, Medscape, Gilead; Financial Interests, Institutional, Other: Novartis, Roche, Seattle Genetics, Genentech. G. Rinnerthaler: Financial Interests, Personal and Institutional, Other: Roche, Pierre Fabre; Financial Interests, Personal, Other: AstraZeneca, Novartis, BMS, Roche, Pfizer, Eli Lilly, MSD, Daiichi Sankyo. M. Schmidt: Financial Interests, Personal, Other: Amgen, Seagen; Financial Interests, Personal and Institutional, Other: Pierre Fabre, Roche, Pfizer, Novartis, AstraZeneca, Eisai, Pantarhei, BioNTech; Financial Interests, Institutional, Other: Genentech; Non-Financial Interests, Personal, Other: Roche, Pfizer, Pantarhei, BioNTech; Non-Financial Interests, Personal, Other, Issued patent EP: 2951317, Issued patent EP: 2390370: Other. K. Zaman: Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Institutional, Other: Eli Lilly, Novartis, MSD Oncology, Mylan, Daiichi Sankyo, Pierre Fabre, Genentech. T. Schinköthe: Financial Interests, Personal, Full or part-time Employment: CANKADO Service GmbH; Financial Interests, Personal, Ownership Interest: CANKADO Service GmbH. D. Lüftner: Financial Interests, Institutional, Other: Novartis; Financial Interests, Personal, Other: Amgen, Pfizer, GSK, Loreal, Teva, Gilead, Sanofi Aventis, Daiichi Sankyo, Samsung, AstraZeneca, Novartis. All other authors have declared no conflicts of interest.
165MO - Trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients (pts) with active brain metastases: Primary outcome analysis from the TUXEDO-1 trial (ID 13)
- Rupert Bartsch (Vienna, Austria)
- Anna Sophie Berghoff (Vienna, Austria)
- Julia Furtner (Vienna, Austria)
- Maximilian Marhold (Vienna, Austria)
- Elisabeth S. Bergen (Vienna, Austria)
- Sophie Roider-Schur (Vienna, Austria)
- Angelika M. Starzer (Vienna, Austria)
- Heidrun Forstner (Vienna, Austria)
- Beate Rottenmanner (Vienna, Austria)
- Karin Dieckmann (Vienna, Austria)
- Zsuzsanna A. Bago-Horvath (Vienna, Austria)
- Georg Widhalm (Vienna, Austria)
- Aysegül Ilhan-Mutlu (Vienna, Austria)
- Christoph Minichsdorfer (Vienna, Austria)
- Thorsten Fuereder (Vienna, Austria)
- Christian F. Singer (Vienna, Austria)
- Ansgar Weltermann (Linz, Austria)
- Rainer Puhr (Vienna, Austria)
- Matthias Preusser (Vienna, Austria)
Abstract
Background
Brain metastases (BM) are a frequent and devastating complication of HER2-positive breast cancer (BC). T-DXd is an antibody-drug conjugate with high activity in pretreated pts but information regarding activity in active BM is limited. Therefore, the prospective, single-arm, phase II TUXEDO-1 trial investigated T-DXd in HER2-positive BC pts with active BM.
Methods
TUXEDO-1 included adult pts with HER2-positive BC and newly diagnosed untreated BM or BM progressing after local therapy, prior exposure to trastuzumab and pertuzumab, and no indication for immediate local therapy. The primary endpoint was intracranial response rate (RR) centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria. Secondary endpoints consisted of extracranial RR, progression-free survival (PFS), overall survival, safety, and quality-of-life. Based on a Simon’s two-stage design (RR under alternative hypothesis >60%; RR under null hypothesis <26%), a total number of 15 pts were enrolled. The null hypothesis was to be rejected with a type I error rate of 5% and a power of 80% if at least 7 responses were observed.
Results
As of December 29th, 2021, all 15 pts had received at least one dose of T-DXd (60% progressive BM, 70% prior T-DM1). One patient initially assessed as having parenchymal BM was found to have dural metastasis upon restaging and was excluded from efficacy analyses. In the intention-to-treat population, intracranial RR was 73.3% (11/15) (per protocol population: 78.6% [11/14]). At 11 months median follow-up, PFS was 14 months (95% CI 8.48-19.52); two pts died from disease progression. Main non-haematological toxicities consisted of grade 1/2 fatigue (86.7%), nausea (46.7%), and diarrhoea (26.7%). Dose reductions were required in 9 pts; 4 pts had serious adverse events. Grade 2 interstitial lung disease and a symptomatic drop of left-ventricular ejection fraction were observed in one patient each.
Conclusions
In the TUXEDO-1 study, T-DXd yielded high intracranial response rates. Data suggest that T-DXd achieves significant therapeutic effects in the central nervous system and should thus be further explored in this context.
Clinical trial identification
NCT04752059.
Legal entity responsible for the study
Medical University of Vienna, Department of Medicine 1.
Funding
Daiichi Sankyo.
Disclosure
R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. M. Marhold: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: MEDmedia; Financial Interests, Personal and Institutional, Other: Amgen; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Daiichi; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Eisai. Z.A. Bago-Horvath: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal and Institutional, Other: Daiichi. T. Fuereder: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Accord; Financial Interests, Personal, Invited Speaker: Merck Darmstadt; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Darmstadt. C.F. Singer: Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Advisory Board, ADVISORY FUNCTION: NOVARTIS; Financial Interests, Personal, Advisory Board, ADVISORY ROLE: ROCHE; Financial Interests, Personal, Other, STUDY SUPPORT: PFITZER; Financial Interests, Personal, Advisory Board, ADVISORY, SPEAKER HONORARIES, STUDY SUPPORT: ASTRAZENECA; Financial Interests, Personal, Invited Speaker, STUDY COORDINATOR: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: ASTRAZENECA; Non-Financial Interests, Project Lead, REGISTER: PFITZER. M. Preusser: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: GLG; Financial Interests, Personal, Invited Speaker: CMC contrast; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Mundipharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other: BMJ journals; Financial Interests, Personal, Writing Engagements: MedMedia; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MEDahead; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Tocagen; Financial Interests, Personal, Invited Speaker: Adastra; Financial Interests, Personal, Invited Speaker: Gan & Lee Pharmaceuticals. All other authors have declared no conflicts of interest.
177P - Low HER2 expression does not influence prognosis in metastatic triple-negative breast cancer: results from an international, multicenter analysis coordinated by the Austrian Group Medical Tumor Therapy (AGMT) (ID 185)
- Simon Peter Gampenrieder (Salzburg, Austria)
- Vincent Dezentjé (Amsterdam, Netherlands)
- Matteo Lambertini (Genoa, Italy)
- Alexandre De Nonneville (Marseille, France)
- Maximilian Marhold (Vienna, Austria)
- Fanny Le Du (Rennes, France)
- Cristina Saavedra Serrano (Madrid, Spain)
- Diogo Alpuim Costa (Lisbon, Portugal)
- Eva Blondeaux (Genova, Italy)
- Lucia Del Mastro (Genova, Italy)
- François Bertucci (Marseille, France)
- Anthony Gonçalves (Marseille, France)
- Rupert Bartsch (Vienna, Austria)
- Antoine Deleuze (Rennes, France)
- Alfonso Cortes Salgado (Madrid, Spain)
- Marina Vitorino (Amadora, Portugal)
- Christoph Tinchon (Leoben, Austria)
- Ladislav Pecen (Prague, Czech Republic)
- Gabriel Rinnerthaler (Salzburg, Austria)
- Richard Greil (Salzburg, Austria)
Abstract
Background
Triple-negative breast cancer (TNBC) is associated with poor prognosis. Therefore, new treatment options are urgently needed. About 35% of triple-negative primary tumors show a low expression of HER2 (HER2-low), a potential target for anti-HER2-drugs currently under investigation. In contrast to early breast cancer, little is known about the frequency and the prognostic value of HER2-low in metastatic TNBC.
Methods
In this international, multicenter analysis, we retrospectively evaluated TNBC patients from five European countries (Austria, France, Italy, Portugal, and Spain). Triple-negativity had to be shown in a metastatic site or in the primary breast tumor diagnosed simultaneously or within 3 years prior to metastatic disease. HER2-low was defined as immunohistochemically (IHC) 1+ or 2+ and lack of HER2 gene amplification measured by in-situ hybridization. HER2-0 was defined as IHC 0+. Univariable survival probabilities were calculated by the Kaplan-Meier method and compared by the log-rank test. Multivariable hazard ratios were estimated by Cox regression models.
Results
In total, 691 patients, diagnosed between Jan/2006 and Feb/2021, were evaluable. The incidence of HER2-low was 32.0% (95%CI 28.5-35.5%), with similar proportions in samples from metastatic sites (n=265; 29.8%; 95%CI 24.3-35.3%) and primary tumors (n=425; 33.4%; 95%CI 28.9-37.9%; P=0.324). Median OS in HER2-low and HER2-0 TNBC was 18.6 months (95% CI 16.5-20.3) and 16.1 months (95% CI 14.5-18.6), respectively, which was not statistically significantly different (HR 1.00; 95%CI 0.83-1.19; P=0.969). Similarly, in multivariable analysis HER2-low had no significant impact on OS (HR 0.95; 95%CI 0.79-1.13; P=0.545). In addition, we did not identify a difference in prognosis between HER2 IHC 0/1+ and IHC 2+ tumors (median OS 16.8 vs. 18.2 months; HR 0.89; 95%CI 0.69-1.17; P=0.414).
Conclusions
In this dataset of metastatic TNBC, the largest published until now, the frequency of HER2-low was 32.0%, which is similar as reported in early TNBC populations. In contrast to the early stages, HER2-low did not influence OS in metastatic TNBC.
Legal entity responsible for the study
Austrian Study Group of Medical Tumor Therapy (AGMT).
Funding
Austrian Study Group of Medical Tumor Therapy (AGMT), Grant for statistics by Daiichy Sankyo.
Disclosure
S.P. Gampenrieder: Financial Interests, Personal, Invited Speaker: Travel Grant; Financial Interests, Personal, Advisory Board: Novartis, Roche, BMS, AstraZeneca, MSD, Pfizer, Lilly, Seagen, Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Personal, Other, Travel Grant: Roche, Amgen, Shire, Novartis, Pfizer, Bayer, Celgene, Daiichi Sankyo. V. Dezentjé: Financial Interests, Personal, Other, Honoraria: Roche, Daiichi Sankyo. M. Lambertini: Financial Interests, Personal, Other, Honoraria: Roche, Sandoz, Takeda, Pfizer, Eli Lilly, and Novartis; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Eli Lilly, and Novartis. A. de Nonneville: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly; Financial Interests, Institutional, Other, Travel Grant: Amgen, Daiichi Sankyo. M. Marhold: Financial Interests, Personal, Other, Honoraria: Roche, Eli Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Pfizer, MSD, Medmedia; Financial Interests, Personal, Advisory Board: Roche, Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Other, Travel grant: Amgen, Roche, Novartis, Pierre Fabre, Daiichi Sankyo. F. Le Du: Financial Interests, Personal, Other, Honoraria: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Sandoz, AMGEN; Financial Interests, Personal, Advisory Board: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Sandoz; Financial Interests, Personal, Other, Travel Grant: Novartis, Roche, Daiichi, Pfizer, Lilly, Seagen, Pierre Fabre, Amgen. C. Saavedra Serrano: Financial Interests, Personal, Other, Travel Grant: Lilly, Pfizer. D. Alpuim Costa: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Merck KGaA, Novartis, NTT DATA, Pfizer, Uriage; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme, Novartis, Pfizer; Financial Interests, Personal, Research Grant: Cuf Oncologia, AstraZeneca; Financial Interests, Personal, Other, Travel Grant: Daiichi Sankyo, Merck KGaA, Merck Sharp & Dohme, Novartis, OM Pharma; Financial Interests, Personal, Full or part-time Employment: NTT DATA. L. Del Mastro: Financial Interests, Personal, Other, Honoraria: Roche, Novartis, Pfizer, MSD, Genomic Health, Takeda, Ipsen, Eisai, Eli Lilly and Celgene. F. Bertucci: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly. A. Gonçalves: Financial Interests, Institutional, Research Grant: Pfizer, Novartis, Lilly; Financial Interests, Personal and Institutional, Other, Travel Grant: Novartis. R. Bartsch: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Daiichi Sankyo, Eisai, Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Puma, Roche, Seagen; Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Personal, Research Grant: Daiichi Sankyo, MSD, Novartis, Roche; Financial Interests, Personal, Other, Travel Grant: Roche, Daiichi Sankyo, Lilly, Pfizer. A. Cortés Salgado: Financial Interests, Personal, Other, Honoraria: GSK, AstraZeneca, Roche, MSD, Eisai; Financial Interests, Personal, Advisory Board: Clovis, Lilly, Pfizer, GSK, Ferrer, Roche; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel Grant: Roche, Daiichi Sankyo, Pfizer. L. Pecen: Financial Interests, Personal, Other, Honoraria: Daiichi Sankyo, SOTIO Biotech, Beckman-Coulter. G. Rinnerthaler: Financial Interests, Personal, Other, Honoraria: Roche, Gilead, Pfizer, Eli Lilly, Novartis; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Daiichi Sankyo, Pfizer, Pierre Fabre, Eli Lilly, MSD, Novartis, Amgen, Merk. R. Greil: Financial Interests, Personal, Other, Honoraria: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen C., MSD, Merck, Gilead, Daiichi Sankyo, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board: Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen C., MSD, Merck, Gilead, Daiichi Sankyo, Sanofi, Pfizer; Financial Interests, Personal, Other, Travel Grant: Roche,Amgen,Janssen,AstraZeneca. All other authors have declared no conflicts of interest.
195P - REACH AUT: Efficacy and safety of first line (1L) ribociclib (RIB) + endocrine therapy (ET) in HR+, HER2? metastatic breast cancer (MBC) from a real-world (RW) study - 3rd interim analysis (ID 203)
- Christian F. Singer (Vienna, Austria)
- Daniel Egle (Innsbruck, Austria)
- Richard Greil (Salzburg, Austria)
- Edgar Petru (Graz, Austria)
- Leopold Ohler (Vienna, Austria)
- Marija Balic (Graz, Austria)
- Christoph Tinchon (Leoben, Austria)
- Georg Pfeiler (Vienna, Austria)
- Maximilian Marhold (Vienna, Austria)
- Christine Brunner (Innsbruck, Austria)
- Karin Haider (Wiener Neustadt, Austria)
- Arik Galid (Vienna, Austria)
- Ursula Pluschnig (Klagenfurt, Austria)
- Ferdinand Haslbauer (Vöcklabruck, Austria)
- Michael Hubalek (Schwaz, Austria)
- Andreas Redl (Vienna, Austria)
- Julia Flatschacher (Vienna, Austria)
- Shanow Uthman (Vienna, Austria)
- Bernhard Mraz (Vienna, Austria)
- Rupert Bartsch (Vienna, Austria)
Abstract
Background
In 1L setting, RIB is the only CDK4/6 inhibitor that showed a significant overall survival benefit across three phase 3 trials. REACH AUT — the only non-interventional trial on a CDK4/6 inhibitor in Austria to date, evaluated the RW clinical experience of RIB+ET (aromatase inhibitor [AI] or Fulvestrant [FUL]) in pre-, peri- or postmenopausal patients (pts) with HR+, HER2– MBC.
Methods
Pts with HR+, HER2‒ MBC with no prior ET for advanced disease were enrolled at 13 sites in Austria. Up to 1L chemotherapy (CT) for MBC was allowed.
Results
At data cutoff (8-Oct-2021), out of 283 analyzed pts (12.4% pre/peri- and 85.2% postmenopausal, 2.4% not known) 52.3% pts received ongoing treatment on RIB+ET. Median duration of follow-up was 14.4 months. Median age was 63 years (<65, n=158; ≥65, n=125); ECOG PS 0: 72.4%; 1: 14.8%; 2: 1.4% 3: 0.4%. Visceral (lung, liver) metastases (mets) were recorded in 116 pts (41.0%) and bone only mets in 81 pts (28.6%). De novo disease was reported in 38.5% pts. Prior adjuvant therapy was received by 48.1% pts (AI: n=72 [25.4%]; tamoxifen: n=62 [21.9%]; CT: n=52 [18.4%]). In the advanced setting, 49 pts (17.3%) received RIB+FUL and 222 pts (78.4%) RIB+AI. Prior CT was received by 5 pts (1.8%). In pts evaluable for response, the objective response rate was 31.4%, clinical benefit rate 45.9% and disease control rate 61.1%. Median progression-free survival (mPFS) was 29.7 months in the overall population and 32.7 months in pts with visceral mets. The 12-month OS rate was 90.3%. Majority of adverse events (AEs) were grade 1 (51.9%) or grade 2 (29.7%). Grade 1 AEs were seen in 214 pts (75.6%), grade 2 in 202 pts (71.4%), grade 3 in 140 pts (49.5%), and grade 4 in 13 pts (4.6%). The most common AE was neutropenia (45.9%). 11.7% pts had hepatobiliary AEs (grade 1: n=9 [3.2%]; grade 2: n=14 [4.9%]; grade 3: n=21 [7.4%]). 11.0% of pts had QTcF prolongation (grade 1: n=24 [8.5%]; grade 2: n=10 [3.5%]; grade 3: n=1 [0.4%]). Therapy interruption was needed in 152 pts (53.7%) and ≥1 dose reduction in 113 pts (39.9%).
Conclusions
In RW setting, RIB+ET shows tolerable safety and a mPFS for 1L pts that is in line with MONALEESA trials. The study follow up is immature to show median OS.
Clinical trial identification
CLEE011AAT01.
Editorial acknowledgement
The authors wish to thank Priscilla Joys MDS and Moumita Samanta PhD of Novartis Healthcare Pvt Ltd (Hyderabad, India), for providing medical editorial assistance in the preparation of this abstract.
Legal entity responsible for the study
Novartis Pharma GmbH, Vienna, Austria.
Funding
Novartis Pharma GmbH, Vienna, Austria.
Disclosure
C.F. Singer: Financial Interests, Research Grant: Novartis, AstraZeneca, Amgen; Financial Interests, Advisory Role, Personal fee: Novartis, AstraZeneca, Amgen, Seagen; Financial Interests, Invited Speaker, Speakers' honorarium: Novartis, AstraZeneca, Amgen, Roche, Seagen, Daiichi Sankyo. D. Egle: Financial Interests, Advisory Role, Consulting fee: AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Roche; Financial Interests, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Amgen, AstraZeneca, Daiichi Sankyo, Gilead, Lilly, MSD, Novartis, Pfizer, Roche, Sandoz; Financial Interests, Other, Support for attending meetings and/or travel: Novartis, Pfizer, Roche. R. Greil: Financial Interests, Research Grant: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Sanofi; Financial Interests, Other, Personal fee, Honoraria, Travel, Accommodations, Expenses: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Sanofi;Financial Interests, Advisory Role: Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, Daiichi Sankyo, Sanofi. E. Petru: Financial Interests, Advisory Board, Payment or honoraria: Novartis; Financial Interests, Other, Payments for Presentations, Support for Attending Several Meetings: Novartis; Other, Member: Frauenkrebshilfe Österreich. M. Balic: Financial Interests, Research Grant: ABCSG, AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Roche, Pfizer, Samsung, Seagen;Financial Interests, Other, Consulting fees, Support for attending meetings and/or travel: AstraZeneca, Eli Lilly, MSD, Pfizer, Roche; Financial Interests, Other, Consulting fees: Daiichi Sankyo, Samsung; Financial Interests, Other, Consulting fees, Support for attending meetings and/or travel, Receipt of drugs: Novartis, Pierre Fabre; Financial Interests, Other, Consulting fees, Receipt of drugs: Seagen; Financial Interests, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Samsung, Seagen; Financial Interests, Advisory Board, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Daiichi Sankyo, Eli Lilly, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen. C. Tinchon: Financial Interests, Research Grant: Novartis. G. Pfeiler: Financial Interests, Research Grant: AstraZeneca, Pfizer, Accord Healthcare, Bondimed, Roche; Financial Interests, Speaker’s Bureau, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Novartis, AstraZeneca, Daiichi, MSD, Merck, Pfizer, Amgen, Accord, Roche, UCB; Financial Interests, Expert Testimony, Payment: Novartis, AstraZeneca, Daiichi, MSD, Merck, Pfizer, Amgen, Accord, Roche, UCB; Financial Interests, Other, Support for attending meetings and/or travel: Novartis, AstraZeneca, Daiichi, MSD, Merck, Pfizer, Amgen, Accord, Roche, UCB. M. Marhold: Financial Interests, Speaker’s Bureau, Payment or Honoraria for Lectures, Presentations, Speakers Bureaus, Manuscript Writing or Educational Events: Roche, Pfizer, MSD, Eli Lilly, Novartis, AstraZeneca, Daiichi Sankyo, Medmedia; Financial Interests, Other, Support for Attending Meetings and/or Travel: Roche, Novartis, Pierre Fabre, Daiichi Sankyo, Eisai. U. Pluschnig: Financial Interests, Advisory Board, Participation in Virtual Scientific Expert Meeting and Payment or Honoraria for Expert Meeting: Novartis. F. Haslbauer: Financial Interests, Speaker’s Bureau, Payment or Honoraria for Lectures, Presentations, Speakers Bureaus, Manuscript Writing or Educational Events: Roche, BMS, Servier; Financial Interests, Other, All support for the present manuscript: Novartis. J. Flatschacher, S. Uthman: Financial Interests, Full or part-time Employment: Novartis. B. Mraz: Financial Interests, Full or part-time Employment: Novartis; Financial Interests, Stocks/Shares, Owner of stocks: Novartis. R. Bartsch: Financial Interests, Other, Personal fees: AstraZeneca, Daiichi, Eisai, Eli Lilly, MSD, Novartis, Pfizer, Pierre Fabre, Roche, Seagen; Financial Interests, Research Grant: Daiichi; Non-Financial Interests, Other, Personal fees: Daiichi. All other authors have declared no conflicts of interest.
Presenter Of 2 Presentations
Clinical Case in TNBC discussion (ID 467)
165MO - Trastuzumab-deruxtecan (T-DXd) in HER2-positive breast cancer patients (pts) with active brain metastases: Primary outcome analysis from the TUXEDO-1 trial (ID 13)
- Rupert Bartsch (Vienna, Austria)
- Anna Sophie Berghoff (Vienna, Austria)
- Julia Furtner (Vienna, Austria)
- Maximilian Marhold (Vienna, Austria)
- Elisabeth S. Bergen (Vienna, Austria)
- Sophie Roider-Schur (Vienna, Austria)
- Angelika M. Starzer (Vienna, Austria)
- Heidrun Forstner (Vienna, Austria)
- Beate Rottenmanner (Vienna, Austria)
- Karin Dieckmann (Vienna, Austria)
- Zsuzsanna A. Bago-Horvath (Vienna, Austria)
- Georg Widhalm (Vienna, Austria)
- Aysegül Ilhan-Mutlu (Vienna, Austria)
- Christoph Minichsdorfer (Vienna, Austria)
- Thorsten Fuereder (Vienna, Austria)
- Christian F. Singer (Vienna, Austria)
- Ansgar Weltermann (Linz, Austria)
- Rainer Puhr (Vienna, Austria)
- Matthias Preusser (Vienna, Austria)
Abstract
Background
Brain metastases (BM) are a frequent and devastating complication of HER2-positive breast cancer (BC). T-DXd is an antibody-drug conjugate with high activity in pretreated pts but information regarding activity in active BM is limited. Therefore, the prospective, single-arm, phase II TUXEDO-1 trial investigated T-DXd in HER2-positive BC pts with active BM.
Methods
TUXEDO-1 included adult pts with HER2-positive BC and newly diagnosed untreated BM or BM progressing after local therapy, prior exposure to trastuzumab and pertuzumab, and no indication for immediate local therapy. The primary endpoint was intracranial response rate (RR) centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria. Secondary endpoints consisted of extracranial RR, progression-free survival (PFS), overall survival, safety, and quality-of-life. Based on a Simon’s two-stage design (RR under alternative hypothesis >60%; RR under null hypothesis <26%), a total number of 15 pts were enrolled. The null hypothesis was to be rejected with a type I error rate of 5% and a power of 80% if at least 7 responses were observed.
Results
As of December 29th, 2021, all 15 pts had received at least one dose of T-DXd (60% progressive BM, 70% prior T-DM1). One patient initially assessed as having parenchymal BM was found to have dural metastasis upon restaging and was excluded from efficacy analyses. In the intention-to-treat population, intracranial RR was 73.3% (11/15) (per protocol population: 78.6% [11/14]). At 11 months median follow-up, PFS was 14 months (95% CI 8.48-19.52); two pts died from disease progression. Main non-haematological toxicities consisted of grade 1/2 fatigue (86.7%), nausea (46.7%), and diarrhoea (26.7%). Dose reductions were required in 9 pts; 4 pts had serious adverse events. Grade 2 interstitial lung disease and a symptomatic drop of left-ventricular ejection fraction were observed in one patient each.
Conclusions
In the TUXEDO-1 study, T-DXd yielded high intracranial response rates. Data suggest that T-DXd achieves significant therapeutic effects in the central nervous system and should thus be further explored in this context.
Clinical trial identification
NCT04752059.
Legal entity responsible for the study
Medical University of Vienna, Department of Medicine 1.
Funding
Daiichi Sankyo.
Disclosure
R. Bartsch: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Daiichi; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Seagen; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Institutional, Funding, Investigator Initiated Trial: Daiichi; Financial Interests, Institutional, Invited Speaker, Drug support for investigator initiated trial: MSD. M. Marhold: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: MEDmedia; Financial Interests, Personal and Institutional, Other: Amgen; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Daiichi; Financial Interests, Personal and Institutional, Other: Roche; Financial Interests, Personal and Institutional, Other: Eisai. Z.A. Bago-Horvath: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal and Institutional, Other: Daiichi. T. Fuereder: Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Accord; Financial Interests, Personal, Invited Speaker: Merck Darmstadt; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck Darmstadt. C.F. Singer: Financial Interests, Personal, Other, consultancy: Amgen; Financial Interests, Personal, Advisory Board, ADVISORY FUNCTION: NOVARTIS; Financial Interests, Personal, Advisory Board, ADVISORY ROLE: ROCHE; Financial Interests, Personal, Other, STUDY SUPPORT: PFITZER; Financial Interests, Personal, Advisory Board, ADVISORY, SPEAKER HONORARIES, STUDY SUPPORT: ASTRAZENECA; Financial Interests, Personal, Invited Speaker, STUDY COORDINATOR: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: AMGEN; Non-Financial Interests, Principal Investigator, STUDY: ASTRAZENECA; Non-Financial Interests, Project Lead, REGISTER: PFITZER. M. Preusser: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: GLG; Financial Interests, Personal, Invited Speaker: CMC contrast; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Invited Speaker: Mundipharma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Other: BMJ journals; Financial Interests, Personal, Writing Engagements: MedMedia; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Invited Speaker: Lilly; Financial Interests, Personal, Invited Speaker: MEDahead; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Tocagen; Financial Interests, Personal, Invited Speaker: Adastra; Financial Interests, Personal, Invited Speaker: Gan & Lee Pharmaceuticals. All other authors have declared no conflicts of interest.