Author Archives: Jessica Ngyuen

EvoPAR-Breast01

EvoPAR-Breast01 Study

STUDY TO EVALUATE THE EFFICACY AND SAFETY OF A COMBINATION THERAPY WITH SARUPARIB AND CAMIZESTRANT IN THE TREATMENT OF PATIENTS WITH HER2-NEGATIVE, ER-POSITIVE, ADVANCED BREAST CANCER

Studiendesign EvoPAR-Breast01

Die EvoPAR-Breast01 ist eine offene (Behandelnde und Patient:innen wissen, welche Therapie verabreicht wird), randomisierte Phase-III-Studie. In der Studie wird eine neue Kombinationstherapie aus Saruparib und Camizestrant mit der bisherigen Standardtherapie verglichen. Die Studie richtet sich an Patient:innen mit metastasiertem oder lokal fortgeschrittenem, hormonrezeptor-positivem, HER2-negativem Brustkrebs, die eine bestimmte genetische Veränderung (BRCA1-, BRCA2- oder PALB2-Mutation) in ihren Krebszellen tragen. Für das frühe Erkrankungsstadium (Adjuvanz) durften die Patientinnen unter bestimmten Voraussetzungen bereits Therapien erhalten haben, aber noch nicht für das fortgeschrittene bzw. metastasierte Stadium (siehe Teilnahmebedingungen).

Was wird in dieser Studie untersucht?

Bei etwa 70 % aller Brustkrebserkrankungen handelt es sich um Hormonrezeptor-positiven (HR+) und HER2-negativen Brustkrebs. Viele dieser Tumore wachsen durch das Hormon Östrogen. Aktuelle Standardtherapien bei fortgeschrittenem Brustkrebs kombinieren eine endokrine Therapie (also eine Antihormontherapie) mit einem Medikament, das bestimmte Wachstumssignale in den Tumorzellen blockiert – sogenannte CDK4/6-Inhibitoren.

Die EvoPAR-Breast01-Studie richtet sich speziell an Patient:innen, bei denen im Tumor eine genetische Veränderung (Mutation) im BRCA1-, BRCA2- oder PALB2-Gen nachgewiesen wurde. Diese Gene sind normalerweise dafür zuständig, Schäden an der DNA zu reparieren. Ist ihre Funktion gestört (auch „Loss of Function“ genannt), kann das zur Entstehung und zum Wachstum von Krebszellen beitragen.

Saruparib gehört zu der Medikamentenklasse der PARP-Inhibitoren, welche gezielt Krebszellen mit DNA-Reparaturdefekten (z. B. durch BRCA-Mutationen) angreifen und zum Absterben bringen können.
Camizestrant ist ein sogenannter Estrogen-Rezeptor-Degrader, ein modernes Medikament, das den Östrogenrezeptor auf Krebszellen zerstört und so das Tumorwachstum bremsen kann.

Was ist das Ziel der Studie?

Hauptziel der Studie ist es zu untersuchen, wie lange der Krebs unter der jeweiligen Behandlung nicht weiter wächst – auch progressionsfreies Überleben (PFS) genannt. Die Untersuchung erfolgt dabei durch ein unabhängiges Expertenteam mittels bildgebender Verfahren (z. B. CT, MRT). Außerdem wird die gesamte Überlebenszeit, sowie die Zeit bis zum zweiten Progress, die Zeit bis zur Verabreichung der nächsten Chemotherapie und weitere wichtige Fragestellungen beobachtet.

Wie ist der Ablauf der Studie?

An der Studie nehmen etwa 500 Patient:innen teil. Sie werden nach dem Zufallsprinzip in drei Gruppen, sogenannte Behandlungsarme, aufgeteilt (randomisiert im Verhältnis 2:2:1):

  • Arm 1 (neue Kombinationstherapie)
    Saruparib + Camizestrant

  • Arm 2 (Standardtherapie)
    CDK4/6-Inhibitor (z. B. Palbociclib, Ribociclib oder Abemaciclib) + Standard-Endokrine Therapie (z. B. Fulvestrant oder einen Aromatasehemmer: Letrozol, Anastrozol oder Exemestan)
  • Arm 3 (Kombinationsvergleich)
    CDK4/6-Inhibitor (z. B. Palbociclib, Ribociclib oder Abemaciclib) + Camizestrant

Alle Medikamente werden entweder als Tablette oder Infusion verabreicht, abhängig vom jeweiligen Studienarm. Die Gabe der jeweiligen Therapie erfolgt in jedem Studienarm bis zum Voranschreiten der Erkrankung.

Die Patient:innen werden regelmäßig während der Studie und bis zu 30 Tage nach der letzten Medikamenteneinnahme beobachtet, um die Wirksamkeit und Verträglichkeit der Therapien zu erfassen. Auch danach erkundigen sich die Behandler:innen etwa alle 12 Wochen über den Zustand der Patient:in, bis die Studie offiziell abgeschlossen ist.

Gibt es Risiken?

Über mögliche Risiken bzw. Nebenwirkungen, die mit der Teilnahme verbunden sind, werden Sie im Rahmen eines Aufklärungsgesprächs informiert.

Teilnahmevoraussetzungen

An dieser Studie können Frauen und Männer ab einem Alter von 18 Jahren teilnehmen, mit:

  • Metastasiertem Brustkrebs (mBC); dabei kann der Brustkrebs entweder:

(1) von Anfang an als metastasiert oder lokal fortgeschritten diagnostiziert worden sein oder

(2) der Brustkrebs kann zuvor in der Adjuvanz (= zusätzliche Behandlung nach der Operation, z. B. Chemotherpie oder Hormontherapie) mit dem Ziel auf Heilung therapiert worden sein.

– Falls eine Chemotherapie in der Adjuvanz gegeben wurde, muss diese jedoch mehr als 84 Tage her sein.

– Falls in der Adjuvanz PARP-Inhibitoren, CDK4/6-Inhibitoren oder orale SERDs gegeben wurden, müssen diese diese Therapien mehr als 365 Tage zurückliegen.

  • Für die metastasierte Situation durfte noch keine Therapie (also Erstlinientherapie) gegeben worden sein
  • Der Tumor muss HR-positiv, HER-2 negativ sein
  • Der Tumor muss eine BRCA1- oder BRCA2- oder PALB2 Mutation aufweisen, die entweder in der Keimbahn (angeboren oder vererbbar) oder im Tumor (somatisch) nachgewiesen werden kann

Darüber hinaus gibt es aber auch noch weitere Kriterien, die für eine Teilnahme an der Studie erfüllt sein müssen. Interessierte Patient:innen sollten mit den Prüfärzt:innen an einem Studienzentrum sprechen, ob diese Studie für Sie in Frage kommt.

Wo kann ich an dieser Studie teilnehmen?
Weitere Informationen zu teilnehmende Zentren finden Sie hier:
https://studienportal-brustkrebs.de/deutschlandkarte

Diese Studie wird unterstützt von:

Astra Zeneca Firmenlogo

CAPItello-292

CAPItello-292 Study

THERAPY STUDY TO EVALUATE A NEW COMBINATION THERAPY WITH CAPIVASERTIB, FULVESTRANT AND A CDK4/6 INHIBITOR IN PATIENTS WITH HER2-NEGATIVE, HORMONE RECEPTOR-POSITIVE ADVANCED BREAST CANCER

Studiendesign der CAPItello-292 Studie

Die CAPItello-292 ist eine offene (Behandelnde und Patient:innen wissen, welche Therapie verabreicht wird), randomisierte Phase-III-Studie. Untersucht wird eine neue Kombinationstherapie mit Capivasertib, Fulvestrant und einem CDK4/6-Inhibitor (entweder Palbociclib oder Ribociclib). Diese Kombination wird verglichen mit der bisherigen Standardtherapie aus Fulvestrant und einem CDK4/6-Inhibitor – bei Patient:innen mit einem fortgeschrittenen oder metastasierten, Hormonrezeptor-positiven (HR+), HER2-negativen Brustkrebs, der nach einer vorherigen Antihormonbehandlung erneut aufgetreten ist oder fortgeschritten war.

Was wird in dieser Studie untersucht?

Hormonrezeptor-positiver, HER2-negativer Brustkrebs ist die häufigste Form von Brustkrebs. Diese Tumore wachsen oft unter dem Einfluss von Hormonen wie Östrogen. In der Behandlung fortgeschrittener Erkrankungen ist eine Kombination aus Antihormontherapie (z. B. Fulvestrant) und einem CDK4/6-Inhibitor (z. B. Palbociclib oder Ribociclib) heute der Behandlungsstandard.

In der CAPItello-292-Studie wird zusätzlich das neue Medikament Capivasertib getestet. Es gehört zur Gruppe der AKT-Inhibitoren. AKT ist ein Protein, das eine zentrale Rolle in Signalwegen spielt, die das Wachstum und Überleben von Tumorzellen fördern können. Capivasertib blockiert dieses Protein und könnte so das Wachstum von Krebszellen bei bestimmten Patient:innen zusätzlich hemmen.

Capivasertib wurde bereits in früheren Studien (z. B. CAPItello-291) in Kombination mit Fulvestrant untersucht und zeigte dort vielversprechende Ergebnisse, insbesondere bei Patient:innen mit bestimmten genetischen Veränderungen (z. B. Veränderung im PIK3CA-/AKT1- oder im PTEN-Gen).

Was ist das Ziel der Studie?

Hauptziel der Studie ist es zu untersuchen, wie lange die Krankheit unter der jeweiligen Therapie nicht weiter fortschreitet (sogenanntes progressionsfreies Überleben, kurz PFS). Diese Untersuchung erfolgt durch ein unabhängiges Expertenteam anhand bildgebender Verfahren (z. B. CT, MRT). Die Ergebnisse sollen zeigen, ob Capivasertib in Kombination mit der Standardtherapie eine bessere Kontrolle des Tumors ermöglicht als die Standardtherapie allein. Außerdem wird die gesamte Überlebenszeit, die gesundheitsbezogene Lebensqualität der Patient:innen und weitere wichtige Fragestellungen beobachtet.

Wie ist der Ablauf der Studie?

Insgesamt sollen Patient:innen in zwei Gruppen (Arme) aufgeteilt werden – per Zufallsprinzip (randomisiert) im Verhältnis von 1:1.

  • Arm A (neue Kombinationstherapie):
    • Capivasertib (Tablette) +
    • Fulvestrant (Antihormontherapie, Injektion) +
    • CDK4/6-Inhibitor: Palbociclib oder Ribociclib (Tablette)
    • + ggf. LHRH-Agonist*
  • Arm B (Standardtherapie):
    • Fulvestrant +
    • CDK4/6-Inhibitor: Palbociclib oder Ribociclib
    • + ggf. LHRH-Agonist*

*Prä- und perimenopausale Frauen sowie Männer erhalten zusätzlich einen sogenannten LHRH-Agonisten, der die körpereigene Hormonproduktion vorübergehend unterdrückt – es sei denn, bei Frauen wurde bereits eine operative Entfernung der Eierstöcke (Ovarektomie) durchgeführt.

In beiden Studienarmen erfolgt die Therapie bis zum Voranschreiten der Erkrankung, dem Auftreten unakzeptabler Nebenwirkungen oder dem Widerruf der Einverständniserklärung.

Gibt es Risiken?

Über mögliche Risiken bzw. Nebenwirkungen, die mit der Teilnahme verbunden sind, werden Sie im Rahmen eines Aufklärungsgesprächs informiert.

Teilnahmevoraussetzungen

An dieser Studie können Frauen und Männer ab einem Alter von 18 Jahre teilnehmen, mit:

  • lokal fortgeschrittenem oder metastasiertem Brustkrebs
  • HR-positiv, HER-2 negativ
  • einem Krankheitsrückfall während oder innerhalb von 12 Monaten nach Abschluss einer (neo-) adjuvanten Antihormontherapie (im Rahmen der Behandlung eines frühen, noch nicht metastasiertem Brustkrebs)
  • keine vorherige Behandlung mit einem CDK4/6-Inhibitor bei metastasiertem Brustkrebs (mind. 12 Monate krankheitsfreies Intervall, wenn ein CDK4/6-Inhibitor adjuvant gegeben worden ist)
  • keine Vorbehandlung mit systemischen AKT Inhibitoren, PI3KInhibitoren (z.B. Alpelisib) und mTOR Inhibitoren (z.B. Everolimus)
  • maximal einer vorangegangenen Chemotherapie

Hinweis: Auch Patient:innen mit Typ-2-Diabetes können teilnehmen, wenn ihre Blutzuckerwerte gut eingestellt sind und sie nicht mit Insulin behandelt werden.

Darüber hinaus gibt es aber auch noch weitere Kriterien, die für eine Teilnahme an der Studie erfüllt sein müssen. Interessierte Patient:innen sollten mit den Prüfärzt:innen an einem Studienzentrum sprechen, welche prüfen können, ob diese Studie für Sie in Frage kommt.

Wo kann ich an dieser Studie teilnehmen?
Weitere Informationen zu teilnehmende Zentren finden Sie hier:
https://studienportal-brustkrebs.de/deutschlandkarte

Diese Studie wird unterstützt von:

Astra Zeneca Firmenlogo

New Approaches against Metastatic Breast Cancer: Mini-Tumors from Circulating Tumor Cells

New Approaches against Metastatic Breast Cancer: Mini-Tumors from Circulating Tumor Cells

On January 3, 2025, the German Cancer Research Center (DKFZ) published an exciting press release on the results of a DKFZ research team that was able to develop a new approach to specifically eliminate tumor cells using blood samples from breast cancer patients.

Here is the press release:

Circulating tumor cells in the blood are the “germ cells” of breast cancer metastases. They are very rare and could not be propagated in cell culture dishes until now, which made the research of therapy resistances difficult. A team from the German Cancer Research Center (DKFZ), the Heidelberg Stem Cell Institute HI-STEM*, and the NCT Heidelberg** has now succeeded for the first time in cultivating stable tumor organoids directly from blood samples of breast cancer patients. Using these mini-tumors, the researchers were able to decipher a molecular signaling pathway that ensures the survival and therapy resistance of cancer cells. With this knowledge, the researchers succeeded in developing an approach to specifically eliminate the tumor cells in laboratory experiments.

Metastases are dangerous offshoots of tumors that spread to vital organs such as the liver, lungs, or brain and are usually difficult to treat. Even though the prognosis for breast cancer patients has significantly improved in recent decades, metastatic breast cancer still poses a major challenge, as metastases often respond only temporarily to therapies.
Cancer cells that detach from the primary tumor and migrate into other organs via the bloodstream are considered triggers of breast cancer metastases. These circulating cancer cells (CTCs) are extremely rare and hide among the billions of blood cells circulating in the blood vessels.

Andreas Trumpp, head of department at DKFZ and HI-STEM director, had already shown several years ago that only a few of the circulating tumor cells are capable of forming a new secondary tumor in another organ. These mostly therapy-resistant “germ cells” of metastases are very rare, difficult to isolate, and could not be propagated in the laboratory until now. “This makes it difficult to specifically develop new therapies that directly attack the metastasis-causing cells. However, if we understand how these cells survive the initial therapy and what drives their growth, we could combat the formation of breast cancer metastases at the root and perhaps even prevent them entirely one day,” explains the first author of the work, Roberto Würth from Trumpp’s research department.
The team around Andreas Trumpp has succeeded for the first time worldwide in propagating CTCs from blood samples of breast cancer patients and cultivating them as stable tumor organoids in cell culture. Until now, an detour was always necessary, namely the complex and lengthy propagation of CTCs in immunodeficient mice. To understand how tumor cells become resistant to therapies, researchers need tumor material from different time points in the course of the disease. Unlike surgical removal of tissue samples (biopsy), blood draws are simple and can be performed repeatedly.

The three-dimensional and patient-specific mini-tumors can be cultivated multiple times during the disease from blood samples and are excellently suited to investigate the molecular mechanisms that enable the survival of tumors despite therapy. Preclinical tests for the effectiveness of already available cancer drugs can also be carried out quickly and on a large scale on organoids in cell culture.
The clinical registry study CATCH (ClinicalTrials.gov ID: NCT05652569) at NCT Heidelberg analyzes the genetic diversity of tumor cells from breast cancer patients. Thanks to the successful cultivation of the organoids, the interdisciplinary research team around Trumpp, in close cooperation with the CATCH study, was able to identify a key signaling pathway that ensures the growth and survival of breast cancer CTCs in the blood. The protein NRG1 (Neuregulin 1) acts like a vital ‘fuel’. It binds to the HER3 receptor on the cancer cells and, together with the HER2 receptor, activates signaling pathways that ensure cell growth and survival. What’s also exciting: Even if this fuel runs out or the receptors are blocked by medication, the cells find new tricks. An alternative signaling pathway, controlled by the Fibroblast Growth Factor Receptor 1 (FGFR1), steps in and ensures growth and survival.

“Tumors react to external influences, for example, targeted therapies against HER2, by using such ‘bypass roads’. This is a crucial mechanism in the development of therapy resistance,” explains Roberto Würth. But there are ways out: The researchers showed on the organoids that a combined blockade of both signaling pathways (NRG1-HER2/3 and FGFR) can effectively stop the proliferation of tumor cells and induce cell death.

Andreas Trumpp summarizes: “The ability to cultivate CTCs from the blood of breast cancer patients at different time points as tumor organoids in the laboratory is a decisive breakthrough. This allows us to investigate much better how tumor cells become resistant to therapies. On this basis, we can develop new treatments that may also specifically kill resistant tumor cells. Another conceivable approach is to adapt existing therapies in such a way that the development of resistances and metastases is reduced or even prevented from the outset. Since the organoids are specific for each patient, the method is suitable for identifying or developing individually tailored therapies that are optimally adapted to the individual disease.” Before the method can be used in the care of breast cancer patients, it must first be tested in clinical studies.

*The Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH was founded in 2008 as a public-private partnership by DKFZ and Dietmar Hopp Foundation

** The National Center for Tumor Diseases (NCT) Heidelberg is a long-term cooperation between the German Cancer Research Center (DKFZ), the University Hospital Heidelberg (UKHD), the Medical Faculty of Heidelberg University, and the Thoraxklinik Heidelberg.

Source: DKFZ

CAMBRIA-2

CAMBRIA-2 Study

THERAPEUTIC STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CAMIZESTRANT IN THE TREATMENT OF PATIENTS WITH ER-POSITIVE, HER2-NEGATIVE EARLY BREAST CANCER

Die CAMBRIA-2 ist eine offene (behandelnde Ärzt:innen und Patient:innen kennen den zugeordneten Behandlungsarm), randomisierte (zufällige Zuteilung in einen Behandlungsarm) Phase-3-Studie zur Bewertung der Wirksamkeit und Sicherheit des Medikaments Camizestrant mit oder ohne Kombination mit Abemaciclib, im Vergleich zur Standard-Antihormontherapie bei Patient:innen mit frühem Brustkrebs, welcher Östrogenrezeptoren aufweist (ER+), aber keine humanen epidermalen Wachstumsfaktor-Rezeptoren-2 (HER2-) und die ein mittleres oder hohes Risiko für einen Krankheitsrückfall (Rezidiv) aufweisen. Die Patient:innen müssen bereits die Operation mit oder ohne Radiotherapie/Chemotherapie abgeschlossen haben und es darf kein Hinweis auf ein Fortschreiten der Erkrankung vorliegen.

Was wird in dieser Studie untersucht?

Hormonrezeptor-positive (HR+, dazu zählt auch ER+), HER2- Tumore machen nach aktuellem Stand mehr als 75 % aller Brustkrebsfälle aus. Aktuelle Leitlinien empfehlen für diese Tumore eine kombinierte Behandlung mit einer endokrinen Therapie, z. B. mit einem Aromatasehemmer und einem Hemmstoff gegen bestimmte Proteine, die sogenannten Cyclin-abhängigen Kinasen 4 und 6 (CDK4/6i).

Abemaciclib ist ein solcher CDK4/6i, welcher die Aktivität der CDK4 und CDK6 Proteine in Tumorzellen hemmt, somit den Zellzyklus der Tumorzelle stört und das Tumorwachstum einschränken kann. Das Medikament wird bereits eingesetzt als Erstlinien-Behandlung von metastasiertem (in andere Organe gestreuten) HR+/HER2-Brustkrebs.

Camizestrant ist ein orales Medikament (Tablette) der nächsten Generation, das Östrogenrezeptoren in Brustkrebszellen zerstört (Östrogen Degrader). Tumore mit Hormonrezeptoren können durch natürlich im Körper vorkommende Hormone (z. B. Östrogen) Wachstumssignale bekommen. Camizestrant soll diese Signalübertragung stören und somit das Tumorwachstum stoppen. In vorangegangenen Studien war dieses Medikament bereits gegen Brustkrebs wirksam (z. B. SERENA-1).

Was ist das Ziel der Studie?

Das primäre Ziel der Studie ist es, die Wirksamkeit, Sicherheit und Verträglichkeit der Therapie mit Camizestrant mit der aktuellen Standard-Antihormontherapie bei Patient:innen mit einem HER2-, ER+ Brustkrebs im Frühstadium zu vergleichen. Dafür wird die Zeit, in der die Krankheit nicht fortschreitet (Auftreten eines Rezidivs oder einer Fernmetastase) gemessen. Zudem werden auch die Gesamtüberlebenszeit und die Verträglichkeit der Therapie untersucht.

Wie ist der Ablauf der Studie?

Patient:innen, die an der Studie teilnehmen können, werden im Verhältnis 1:1 zufällig einem der zwei Behandlungsarme zugeordnet und erhalten:

Arm 1 (Kontrollgruppe)
Standard-Antihormontherapie (mögliche Therapien: Tamoxifen oder Aromataseinhibitoren (Anastrozol, Letrozol, Exemestan)) ( +/- LHRH-Agonisten*) +/- Abemaciclib für 7 Jahre

oder

Arm 2
Camizestrant (+/- LHRH-Agonisten*) +/- Abemaciclib für 7 Jahre

* prä- und perimenopausale Frauen sowie Männer erhalten einen LHRH (Frauen obligatorisch in beiden Armen, bei Männern nur mit Aromataseinhibitoren)

Die Nachbeobachtungszeit für beide Arme beträgt mindestens 7 Jahre.

Gibt es Risiken?

Über mögliche Risiken bzw. Nebenwirkungen, die mit der Teilnahme verbunden sind, werden Sie im Rahmen eines Aufklärungsgesprächs informiert.

Teilnahmevoraussetzungen

An dieser Studie können Frauen und Männer ab einem Alter von 18 Jahre teilnehmen, mit:

  • ER+, HER2− Brustkrebs im Frühstadium
  • Einem mittleren oder hohem Risiko für ein Rezidiv
  • Vollständig abgeschlossener Operation (+/-Radiotherapie) mit oder ohne Chemotherapie
  • Ohne Hinweise auf ein Rezidiv

Darüber hinaus gibt es aber auch noch weitere Kriterien, die für eine Teilnahme an der Studie erfüllt sein müssen. Interessierte Patient:innen sollten mit den Prüfärzt:innen an einem Studienzentrum sprechen, welche prüfen können, ob diese Studie für Sie in Frage kommt.

Wo kann ich an dieser Studie teilnehmen?
Weitere Informationen zu teilnehmende Zentren finden Sie hier:
https://studienportal-brustkrebs.de/deutschlandkarte

Diese Studie wird unterstützt von:

Astra Zeneca Firmenlogo

CAMBRIA-1

CAMBRIA-1 Study

THERAPY STUDY TO EVALUATE THE EFFICACY AND SAFETY OF CAMIZESTRANT IN THE TREATMENT OF PATIENTS WITH ER-POSITIVE, HER2-NEGATIVE EARLY BREAST CANCER

Die CAMBRIA-1 ist eine offene (behandelnde Ärzt:innen und Patient:innen kennen den zugeordneten Behandlungsarm), randomisierte (zufällige Zuteilung in einen Behandlungsarm) Phase-3-Studie zur Bewertung der Wirksamkeit und Sicherheit des Medikaments Camizestrant als verlängerte Antihormontherapie im Vergleich zur Standard-Antihormontherapie bei Patient:innen mit frühem Brustkrebs, welcher Östrogenrezeptoren aufweist (ER+), aber keine humanen epidermalen Wachstumsfaktor-Rezeptoren 2 (HER2-) und die ein mittleres oder hohes Risiko für einen Krankheitsrückfall (Rezidiv) aufweisen. Die Patient:innen müssen bereits die Operation abgeschlossen und danach mit einer Antihormontherapie begonnen haben (für mind. 2 bis max. 5 Jahre) mit oder ohne Cyclin-abhängigem Kinase-4- und -6(CDK4/6)-Inhibitor, unter der die Krankheit nicht fortgeschritten ist.

Was wird in dieser Studie untersucht?

Camizestrant ist ein orales Medikament (Tablette) der nächsten Generation, das Östrogenrezeptoren in Brustkrebszellen zerstört (Östrogen Degrader). Tumore mit Hormonrezeptoren können durch natürlich im Körper vorkommende Hormone (z. B. Östrogen) Wachstumssignale bekommen. Camizestrant soll diese Signalübertragung stören und somit das Tumorwachstum stoppen. In vorangegangenen Studien war dieses Medikament bereits gegen Brustkrebs wirksam (z. B. SERENA-1).

Was ist das Ziel der Studie?

Das primäre Ziel der Studie ist es, die Wirksamkeit, Sicherheit und Verträglichkeit der Therapie mit Camizestrant zu vergleichen mit der aktuellen Standard-Antihormontherapie (Aromatasehemmer oder Tamoxifen) bei Patient:innen mit einem HER2-negativem, ER-positivem Brustkrebs im Frühstadium. Primär wird die Zeit, in der die Krankheit nicht fortschreitet (Auftreten eines Rezidivs oder einer Fernmetastase) gemessen. Zudem werden auch die Gesamtüberlebenszeit und die Verträglichkeit der Therapie untersucht.

Wie ist der Ablauf der Studie?

Patient:innen, die an der Studie teilnehmen können, werden im Verhältnis 1:1 zufällig einem der zwei Behandlungsarme zugeordnet und erhalten:

Arm 1 (Kontrollgruppe)
Fortführung der Standard-Antihormontherapie (mögliche Therapien: Tamoxifen oder Aromataseinhibitoren (Anastrozol, Letrozol, Exemestan) ( +/- LHRH-Agonisten*) für weitere 5 Jahre

oder

Arm 2
Camizestrant 75 mg ( +/- LHRH-Agonisten*) für weitere 5 Jahre

* prä- und perimenopausale Frauen sowie Männer erhalten einen LHRH (Frauen obligatorisch in beiden Armen, sofern die Eierstöcke noch vorliegen, bei Männern nur mit Aromataseinhibitoren)

Die Nachbeobachtungszeit für beide Arme beträgt mindestens 10 Jahre.

Gibt es Risiken?

Über mögliche Risiken bzw. Nebenwirkungen, die mit der Teilnahme verbunden sind, werden Sie im Rahmen eines Aufklärungsgesprächs informiert.

Teilnahmevoraussetzungen

An dieser Studie können Frauen und Männer ab einem Alter von 18 Jahre teilnehmen, mit:

  • ER+, HER2− Brustkrebs im Frühstadium
  • Einem mittleren oder hohem Risiko für ein Rezidiv
  • Vollständig abgeschlossener Operation
  • Mindestens 2 bis maximal 5 Jahren Antihormontherapie (nach Operation)
  • Ohne Hinweise auf ein Rezidiv
  • Planung einer weiteren Behandlung mit Antihormontherapie für 5 Jahre

Darüber hinaus gibt es aber auch noch weitere Kriterien, die für eine Teilnahme an der Studie erfüllt sein müssen. Interessierte Patient:innen sollten mit den Prüfärzt:innen an einem Studienzentrum sprechen, welche prüfen können, ob diese Studie für Sie in Frage kommt.

Wo kann ich an dieser Studie teilnehmen?
Weitere Informationen zu teilnehmende Zentren finden Sie hier:
https://studienportal-brustkrebs.de/deutschlandkarte

Diese Studie wird unterstützt von:

Astra Zeneca Firmenlogo

EMBER-4

EMBER-4 Study

Endocrine therapy with Imlunestrant in high-risk patients
with early ER-positive and HER2-negative breast cancer and
completed endocrine therapy

EMBER-4 is a randomized, unblinded (patients and physicians know the treatment arm at the start of the study) Phase 3 therapy study comparing two endocrine therapies in patients with early estrogen receptor-positive (ER+), HER2-receptor-negative (HER2-) breast cancer who have an increased risk of disease recurrence and who have previously received 2 to 5 years of endocrine therapy after surgery.

What is being investigated in this study?

Breast cancer is diagnosed in most patients at an early stage of the disease. Currently, the standard treatment is surgery followed by endocrine therapy, administered for 5 to 10 years, if the tumor has the following characteristics: early stage, estrogen receptor-positive, and human epidermal growth factor receptor-2-negative (HER2-). If patients have a high risk of recurrence, Abemaciclib (a drug with an inhibitor for a specific protein significantly involved in cell division) can additionally be administered in combination during the first two years. Despite the current standard treatment, a significant proportion of patients experience disease recurrence. Consequently, there is a need to further optimize post-operative treatment and prevent disease recurrence, especially in those patients who have an increased risk of such recurrence. The risk for these patients to develop distant recurrence after 5 years of endocrine therapy depends on the clinico-pathological features at diagnosis, i.e., tumor size, grade, and nodal status.

Imlunestrant belongs to the so-called targeted estrogen receptor degraders. Active substances of this drug class promote the degradation of estrogen receptors on the surface of tumors and thus inhibit their estrogen-dependent growth. Previous studies have indicated that Imlunestrant can specifically stop the cell division of tumor cells, provided the tumor is estrogen receptor-positive.

What is the goal of the study?

The primary goal of this study is to demonstrate that treatment with Imlunestrant has a benefit in efficacy compared to current standard anti-hormone therapy. The study targets patients with an increased risk of disease recurrence, whose tumor is estrogen receptor-positive and HER2-receptor negative, and who have also previously received standard anti-hormone therapy for 2-5 years. Furthermore, the safety and tolerability of the treatments and the quality of life during therapy will be investigated.

How is the study conducted?

Within the study, there are two treatment arms to which patients are randomly assigned in a 1:1 ratio:

Arm 1:
Imlunestrant – oral intake for approx. 5 years

Arm 2:
Tamoxifen or Aromatase Inhibitor (as decided by the treating physicians) – for approx. 5 years

Follow-up for both arms: 5 years

Are there risks?

You will be informed about possible risks or side effects associated with participation during an informational discussion.

Eligibility requirements

Men and women aged 18 and older can participate in this study, with:

  • Diagnosis of ER+, HER2 receptor negative, invasive early-stage breast cancer
  • Increased risk of disease recurrence
  • Resection (surgical removal) without evidence of distant metastases
  • Previously completed standard anti-hormone therapy for 2-5 years

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

Where can I participate in this study?
Further information on participating centers can be found here:
https://studienportal-brustkrebs.de/deutschlandkarte

This study is supported by:

Schriftzug Lilly

SERENA-6 (Recruitment Completed)

SERENA-6 Study

Therapy study to evaluate the potential additional efficacy and safety of Camizestrant in the first-line treatment of patients with HER2-negative, HR-positive, ESR1-mutated breast cancer

Studiendesign für die Serena6-Brustkrebsstudie, eine Grafik

Study recruitment was completed at the end of 2024.

SERENA-6 is a double-blind (neither patient nor treating physicians know the treatment arm), randomized (random assignment to a treatment arm) Phase 3 study to evaluate the efficacy and safety of the drug Camizestrant compared to aromatase inhibitors (Letrozole or Anastrozole) in combination with Palbociclib or Abemaciclib or Ribociclib in patients with metastatic breast cancer that expresses hormone receptors (HR+) but not human epidermal growth factor receptor-2 (HER2-). The cancer must also show a detectable mutation in a specific gene (ESR1m) and the disease must not have progressed under first-line therapy.

What is being investigated in this study?

Hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) tumors currently account for more than two-thirds of all breast cancer cases. Current guidelines recommend a combined treatment for these tumors with endocrine therapy, e.g., an aromatase inhibitor and a cyclin-dependent kinase 4 and 6 (CDK4/6i) inhibitor, as first-line treatment for metastatic (spread to other organs) HR+/HER2- breast cancer. However, in many cases, drug resistance develops over time, which can lead to disease progression. Tumors with mutations in the estrogen receptor-alpha gene (ESR1m) are known to develop resistance to aromatase inhibitors and are also associated with more aggressive disease characteristics, including the development of visceral (affecting abdominal organs) metastases. Consequently, the expected treatment outcomes of subsequent therapies in patients with ESR1m-positive breast cancer are relatively poor, and new approaches are needed to improve treatment outcomes and prevent further disease progression.

Camizestrant is a next-generation oral (tablet) drug that destroys estrogen receptors in breast cancer cells (estrogen degrader). Tumors with hormone receptors can receive growth signals from naturally occurring hormones in the body (e.g., estrogen). Camizestrant is intended to disrupt this signaling and thus stop tumor growth. In previous studies, this drug was already effective against breast cancer (e.g., SERENA-1).

What is the goal of the study?

The primary goal of the study is to compare the efficacy of therapy with Camizestrant along with concurrent administration of a CDK4/6i inhibitor to the current standard therapy in patients with HER2-negative, HR-positive, ESR1-mutated breast cancer in first-line treatment (first treatment of newly diagnosed metastases). Additionally, the patients’ quality of life will be assessed using questionnaires.

How is the study conducted?

Step 1:

First-line breast cancer patients are treated according to current standards (aromatase inhibitor = Anastrozole or Letrozole + CDK4/6i = Palbociclib, Abemaciclib or Ribociclib) and regularly monitored (every 2-3 months) for an ESR1 mutation in cancer cells (via blood samples).

Step 2:

Patients whose tumor cells show an ESR1 mutation during one of these control examinations will be randomly assigned 1:1 to one of two treatment arms and will receive:

Arm A

Camizestrant + the previously received CDK4/6i inhibitor + a placebo as a substitute for the aromatase inhibitor

or

Arm B (Standard Therapy)

The previously received aromatase inhibitor + CDK4/6i inhibitor + a placebo as a substitute for the estrogen receptor degrader

Are there risks?

You will be informed about potential risks or side effects associated with participation during an informational discussion.

Eligibility Criteria

Men and women aged 18 and older can participate in this study, with:

  • Hormone receptor-positive (HR+),
  • HER2-negative,
  • locally advanced (inoperable) or metastatic (spread) breast cancer
  • Current first-line treatment with an aromatase inhibitor (Anastrozole or Letrozole) + CDK4/6i (Palbociclib, Abemaciclib or Ribociclib)
  • ≥ 6 months without signs of disease progression
  • For treatment in Step 2: Confirmed ESR1 mutation of the tumor

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

Where can I participate in this study?
Further information on participating centers can be found here:
https://studienportal-brustkrebs.de/deutschlandkarte

This study is supported by:

Logo von AstaZeneca, eine Pharmafirma

MINERVA Study

MINERVA Study

Combination therapy with Abemaciclib and endocrine therapy in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer with a focus on digital side effect management

The MINERVA study investigates the efficacy and tolerability of Abemaciclib in combination with antihormonal therapy (aromatase inhibitor or Fulvestrant) in patients with locally advanced or metastatic breast cancer (Hormone Receptor +, HER2 -). As part of the study, therapy-related side effects are recorded in a digital patient diary using the free health app CANKADO, processed, and used as a basis for effective, personalized doctor-patient discussions to detect and alleviate symptoms early, thereby improving quality of life. The study includes an additional research project that examines biomarkers in your blood (e.g., tumor components and free tumor cells). The insights gained are intended to help assess the effectiveness of the therapy efficiently and promptly based on blood samples in the future.

What is being investigated in this study?

Abemaciclib is a medication used to treat certain types of breast cancer. It belongs to the group of so-called CDK4/6 inhibitors. CDK4/6 are proteins that play an important role in cell division. In some cancer cells, these proteins are overactive, causing the cells to grow uncontrollably. Abemaciclib inhibits these proteins and can thereby slow down the growth of cancer cells.

Abemaciclib is specifically used to treat hormone receptor-positive, HER2-negative breast cancer. This means that the cancer responds to certain hormones (hormone receptor-positive) and does not have a specific receptor called HER2 on the cell surface (HER2-negative).

The medication is used in combination with other therapies such as aromatase inhibitors or Fulvestrant. These therapies block the production or action of hormones that can promote the growth of cancer cells. Therefore, in the MINERVA study, therapy is carried out with the CDK4/6 inhibitor Abemaciclib in combination with an antihormonal therapy chosen by the physician (aromatase inhibitor or Fulvestrant), according to the approval of Abemaciclib. Thus, the patient always receives a therapy approved and well-studied for this situation.

Check-ups are carried out as part of routine examinations in accordance with guideline recommendations. Additional study-related effort is only required for the documentation of side effects and quality of life questionnaires in the free CANKADO PRO-React app, as well as, if applicable, the collection of blood samples for the translational research project.

What is the goal of the study?

The main focus of this investigation is the calculation of progression-free survival (PFS). Additional goals include the assessment of adverse events (side effects) and the daily documentation of these events through the CANKADO PRO-React health application, including a patient diary and quality of life questionnaires.

CANKADO is a useful digital companion for your breast cancer medication therapy, helping you keep track of your medication intake and your own health. The app combines medical and technical expertise to facilitate communication between doctors and patients and provide effective support during therapy. The parameters recorded in the diary provide a continuous picture of your therapy progress and support your treatment team in preparing for doctor-patient discussions. Extensive reports allow for timely and effective responses to your individual situation. This way, potential side effects can be detected early by the doctor, preventing severe courses. While the use of the app is a focus of the study, it is not mandatory for study participation.

What is the study procedure?

Within the study, there are two treatment arms to which patients are randomly assigned in a 1:1 ratio:

Arm 1:
Abemaciclib daily 2 x 150 mg (oral) + endocrine therapy of choice (aromatase inhibitor/Fulvestrant)

Arm 2:
Abemaciclib + Aromatase Inhibitor (Anastrozole, Letrozole, Exemestane) OR Fulvestrant (possibly GnRH analogues in premenopausal patients)

Are there risks?

You will be informed about possible risks or side effects associated with participation during an informational discussion.

Eligibility Requirements

Women aged 18 and older can participate in this study, with:

  • Initial diagnosis of locally advanced or metastatic breast cancer
  • Hormone receptor-positive, HER2-negative tumor
  • Indication for endocrine-based combination therapy with a CDK4/6 inhibitor

In addition, there are other criteria that must be met for study participation. Interested patients should speak with the investigators at a study center to determine if this study is suitable for them.

Where can I participate in this study?

Further information about the study and participating centers can be found at:
https://www.minerva-studie.de/

This study is conducted by:

https://www.astrazeneca.de/therapiebereiche/onkologie/brustkrebs.html

SURVIVE Study

SURVIVE Study

Breast cancer aftercare study for women and men with early-stage breast cancer, comparing standard aftercare with intensified aftercare

What is being investigated in this study?

The SURVIVE study aims to compare standard aftercare with intensified aftercare in 3,500 patients with early-stage breast cancer. Patients in both groups will receive guideline-compliant aftercare, as they currently do from their treating (gynecologist) physician.

Additionally, both groups will have regular visits to the study center, where, in the intervention group, tumor traces in the blood will be sought using a so-called liquid biopsy. Various tumor markers, circulating tumor cells (CTCs), and circulating tumor DNA will be examined. If an abnormal result is found, imaging (computed tomography of the breast and abdomen, as well as bone scintigraphy) will be arranged for the patient to look for potential recurrences or distant metastases. The liquid biopsy will be supplemented by the regular collection of questionnaires on health status and quality of life.

In the standard aftercare group, blood samples will also be taken, but these will be stored for future research projects and not examined for now. Should abnormal results appear in a later analysis, you will, of course, be contacted.

Assignment to one of the two groups is random.

What is the goal of the study?

Primarily, the SURVIVE study investigates whether there is a difference in overall survival between the study groups and whether distant metastasis can be detected earlier through liquid biopsy. This long-awaited study could lead to a significant change in our current standard aftercare in the future.

What is the study procedure?

Within the study, there are two investigation groups, to which patients are randomly assigned in a 1:1 ratio:

Standard Arm:

Blood samples are regularly collected and stored in a so-called biobank for later (retrospective) analyses. Further imaging diagnostics are performed symptom-oriented according to current guidelines.

Intervention Arm:

The collected blood samples are examined for specific tumor markers, circulating tumor cells (CTCs), and circulating tumor DNA (ctDNA). Should an abnormal finding occur, further examination will be performed using computed tomography of the breast and abdomen (CT Thorax/Abdomen) and bone scintigraphy to rule out disease recurrence.

The visits are the same for both study groups:

  • 2 baseline visits for data collection

thereafter

  • every 3 months in years 1-3
  • every 6 months in years 4-5

thereafter, annual contact (by phone, email, or study center visit) to complete a questionnaire on health status and quality of life, for 5 years.

Are there risks?

You will be informed about potential risks or side effects associated with participation during a detailed consultation.

Participation Requirements

Men and women between 18 and 75 years of age can participate in this study, with:

  • Primary breast cancer with a moderate to high risk of recurrence
  • First-line therapy (chemotherapy, surgery, or radiation therapy, whichever occurred last) completed a maximum of 24 months before study enrollment. Patients with luminal A/B breast cancer (hormone receptor+, HER2-/low) can participate up to 60 months after completion of primary therapy.
  • No evidence of distant metastasis

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the study physicians at a study center to determine if this study is suitable for them.

Where can I participate in this study?

Further information about the study and participating centers can be found at:
https://www.survive-studie.de/patienten.html

The study is conducted by:

https://www.astrazeneca.de/therapiebereiche/onkologie/brustkrebs.html

Funded by:

DESTINY-Breast11 (Recruitment Completed)

DESTINY-Breast11 Study

Therapy with antibody-drug conjugate alone or before chemotherapy plus antibodies compared to chemotherapy plus antibodies in high-risk patients with early-stage HER2-positive breast cancer

Study recruitment was completed in March 2024.

The DESTINY-Breast11 is a randomized, open-label, Phase 3 study on neoadjuvant therapy. Randomized means that treatment assignment is random. Open-label means that both the patient and the study center know the treatment arm, and neoadjuvant refers to medical treatments before surgery. Three different medical treatments (3 “study arms”) are compared in this study. In one study arm, an antibody-drug conjugate is administered. A chemotherapeutic agent is firmly linked to an antibody. This hybrid drug is absorbed by the tumor cell. Subsequently, the chemotherapeutic agent is released inside the tumor cell, thereby destroying the tumor cell. In the second study arm, this antibody-drug conjugate is administered followed by chemotherapy with antibodies. In the third study arm, for comparison with the other two study arms, a classical chemotherapy combined with two antibodies is used (“control arm”). This third treatment arm corresponds to the current standard therapy.

What is being investigated in this study?

In HER2-positive breast cancer, tumor cells show an above-average concentration of a protein called HER2 (human epidermal growth factor receptor). The current standard treatment for HER2-positive breast cancer that can be surgically removed is a combination of the antibodies Trastuzumab, Pertuzumab, and chemotherapy (control arm), followed by surgery. Even after this treatment, breast cancer can recur, which is why better treatments are being sought.

The DESTINY-Breast11 study investigates whether treatment with the antibody-drug conjugate Trastuzumab deruxtecan (T-DXd), either alone or followed by chemotherapy with antibodies, can prevent cancer recurrence. The complete eradication of all tumor cells by medication before surgery (pathological complete remission) indicates that the cancer is less likely to recur.

What is the goal of the study?

The primary goal of this study is to investigate whether treatment before surgery with Trastuzumab deruxtecan, with or without additional chemotherapy and antibodies, more frequently eradicates all tumor cells than standard therapy.

How is the study conducted?

Within the study, there are three treatment arms to which patients are randomly assigned in a 1:1:1 ratio:

Arm 1:
Trastuzumab deruxtecan – intravenous injection every 3 weeks for 8 cycles

Arm 2:
Trastuzumab deruxtecan – intravenous injection every 3 weeks for 4 cycles, followed by combination therapy with: weekly chemotherapy (Paclitaxel) + antibodies (Trastuzumab + Pertuzumab) every 3 weeks for 4 cycles

Arm 3:
Chemotherapy (Doxorubicin + Cyclophosphamide) every 2 weeks for 4 cycles, followed by combination therapy with: weekly chemotherapy (Paclitaxel) + antibodies (Trastuzumab + Pertuzumab) every 3 weeks for 4 cycles

Are there any risks?

You will be informed about potential risks or side effects associated with participation during an informational discussion.

Eligibility Requirements

Men and women aged 18 years or older can participate in this study, with:

  • Operable early-stage breast cancer that has not been previously treated
  • HER2 receptor-positive tumor
  • Hormone receptor-positive (estrogen and/or progesterone receptor-positive) or hormone receptor-negative

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center to determine if this study is suitable for them.

This study is supported by:

DAiichi-Sankyo Logo, Pharmafirma und Forschungsunterstützer für Brustkrebsstudien

PHERGain-2 – Study (Recruitment Completed)

PHERGain-2 Study

A PHASE 2 STUDY TO EVALUATE THE EFFICACY OF A CHEMOTHERAPY-FREE STRATEGY WITH SUBCUTANEOUS FIXED-DOSE TRASTUZUMAB, PERTUZUMAB, AND T-DM1 IN PATIENTS WITH PREVIOUSLY UNTREATED, HER2-POSITIVE EARLY BREAST CANCER

Studiendesign-PHERgain-2-Brustkrebsstudie-Ersttherapie

Recruitment for the study was completed in March 2024.

PHERGain-2 is a multicenter, unblinded, single-arm, single-stage Phase 2 study to evaluate the efficacy of a chemotherapy-free strategy, aiming for pathological complete response (pCR), with Trastuzumab and Pertuzumab (administered as a subcutaneous fixed-dose combination) and T-DM1 in patients with previously untreated HER2-positive early breast cancer.

What is being investigated in this study?

The study investigates the efficacy of a chemotherapy-free strategy that administers Trastuzumab and Pertuzumab as a fixed dose subcutaneously. Pertuzumab and Trastuzumab are antibodies that can bind to HER2 (a specific growth factor hormone receptor). HER2 causes tumor cells to grow faster and is present in large quantities in a quarter of breast cancer cases. By binding the antibodies to HER2, signals that stimulate tumor cell growth are prevented.

This is done in combination with T-DM1, Trastuzumab Emtansine, an antibody-drug conjugate where a drug is linked to an antibody. Antibodies are the “fighters” of the immune system, and in this context, they are also referred to as “armed” antibodies.

What is the goal of the study?

The study investigates the efficacy of this therapy strategy, with the goal being a “pathological complete response”, meaning the regression of invasive cancer cells. The primary analyses include recurrence-free interval, quality of life, and general health status.

What is the study procedure?

The study procedure has only one phase and one investigation arm. First, the HER2 status is examined and an MRI scan is performed. This is followed by the administration of Trastuzumab and Pertuzumab for 8 cycles (one cycle equals 3 weeks) as a fixed subcutaneous dose. After completion of the pre-operative (neoadjuvant) therapy, another MRI scan is performed, then the investigation arm is divided into 3 cohorts, depending on the pathological result:

  • Cohort A: 10 additional 3-week cycles with Trastuzumab and Pertuzumab and, depending on HR status, endocrine therapy (ET, anti-hormonal therapy)
  • Cohort B: T-DM1 with/without ET for 10 cycles
  • Cohort C: T-DM1 with/without ET for 10 cycles, with the option of prior chemotherapy, at the discretion of the physicians

Are there risks?

You will be informed about possible risks or side effects associated with participation during an informational discussion.

Participation Requirements

Women and men aged 18 and older can participate in this study with the following criteria:

  • Histologically confirmed, invasive breast cancer
  • HER2 positive (Immunohistochemistry [IHC] 3+)
  • Tumor size >5 to ≤ 25mm (≤ 30mm by MRI determination)
  • Previously untreated
  • No metastases

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

This study is supported by:

Logo_MEDSIR

PROVIDENCE Study

PROVIDENCE Study

A non-interventional study to collect clinical and quality of life data in patients with HER2+ or HER2-low inoperable or metastatic breast cancer who receive trastuzumab deruxtecan as second-line treatment (for HER2+) or trastuzumab deruxtecan in any line of therapy (for HER2-low) according to the professional information in routine clinical practice

Studiendesign-Providence-Brustkrebsstudie

The PROVIDENCE study is a purely observational study to evaluate the efficacy and safety of trastuzumab deruxtecan (T-DXd) in patients with documented human epidermal growth factor receptor 2 (HER2)-positive or HER2-low inoperable or metastatic breast cancer who receive T-DXd according to the applicable product information in routine clinical practice in Germany. In addition, the quality of life reported by the participating patients in this patient collective will be investigated. Furthermore, patients will be informed about the use of the digital health application (DiGA).

What is the aim of the study?

The primary objective of this study is to determine the time between the start of therapy with T-DXd and the start of a subsequent therapy. The observation period is a maximum of 5 years. Among other things, the health-related quality of life of the patients is also surveyed and their possible changes during the course of therapy are evaluated. In addition, the period in which the disease does not progress further is evaluated.

How is the study conducted?

Participants are divided into two cohorts based on their tumor biology (HER2 status):

Cohort 1 – Patients with confirmed HER2-positive inoperable or metastatic breast cancer who receive T-DXd according to routine clinical practice.

Cohort 2 – Patients with confirmed inoperable or metastatic breast cancer with low HER2 status (HER2-low) who are treated with T-DXd in routine clinical practice.

Are there any risks?

You will be informed about possible risks associated with participation during an explanatory discussion. Since this registry is purely a documentation of clinical routine without planned additional treatment, there is no additional health risk associated with participation.

Participation requirements

Women and men aged 18 years or older can participate in this study, with:

  • recurrent breast cancer that is inoperable or metastatic
  • HER2-positive or HER2-low
  • Pre-treatment for HER2-positive: anti-HER2 targeted therapy
  • Pre-treatment for HER2-low: chemotherapy

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the study doctors at a participating center. They will check whether the PROVIDENCE study is suitable for you.

This study is supported by:

Astra Zeneca Firmenlogo

DESTINY-Breast05 / GBG-103 (Recruitment Completed)

DESTINY-Breast05 / GBG-103

Immunotherapy with antibody-drug conjugates in high-risk patients with early, HER2-positive breast cancer and residual tumor after completed chemotherapy, antibody treatment, and surgery

Study recruitment was completed in March 2024.

DESTINY-Breast05 is a randomized (treatment assignment for the specific patient is by chance), controlled, Phase 3 therapy study comparing two immunotherapies in patients with HER2-positive, early (patient has no metastases except for axillary lymph node metastases) breast cancer. For these patients, chemotherapy + anti-HER2 therapy (antibody administration, a form of immunotherapy) before surgery and the surgery itself have already been performed. Due to a residual tumor in the breast or lymph nodes in the armpits, these patients have a high risk of disease recurrence.

What is being investigated in this study?

A previous study (KATHERINE) with an antibody-drug conjugate (ADC, Trastuzumab Emtansine, T-DM1) was positive and confirmed the benefit of ADCs for patients after completed chemotherapy with antibody administration before surgery (neoadjuvant treatment) and confirmed residual tumor tissue after this treatment and surgery. An antibody-drug conjugate is a compound of a drug bound to an antibody. Most antibody-drug conjugates are chemoimmunoconjugates, meaning that a cell-damaging drug is linked to the antibodies. In this case, they are also referred to as armed antibodies. ADCs specifically bind to tumor cells and then release the drug, which can disrupt tumor growth.

Despite the positive KATHERINE study, there remains an unmet medical need in this patient group, as not all patients could be cured with the previous treatment. Therefore, the DESTINY-Breast05 study is planned for patients who underwent surgery after completed neoadjuvant therapy (chemotherapy + HER2-targeted therapy, Trastuzumab) and in whom a residual tumor was detected despite treatment (in the breast or axillary lymph nodes). The study aims to investigate whether the ADC Trastuzumab Deruxtecan (T-DXd) is more effective than the ADC Trastuzumab Emtansine (T-DM1) in these patients. Treatment with T-DM1 is currently the standard of care and serves as the control in this study.

What is the goal of the study?

The primary goal of this study is to demonstrate that treatment with Trastuzumab Deruxtecan has an advantage in terms of breast cancer progression or recurrence compared to Trastuzumab Emtansine in HER2-positive patients who have a residual tumor after completed chemotherapy and subsequent surgery. Furthermore, the study aims to investigate whether there is a correlation between the individual biomarker status of the tumor (HER2 and hormone receptor status) and the efficacy and/or safety of the treatment.

What is the study procedure?

Within the study, there are two treatment arms to which patients are randomly assigned in a 1:1 ratio:

Arm 1:
Trastuzumab Deruxtecan – intravenous injection every 3 weeks for approx. 12 months

Arm 2:
Trastuzumab Emtansine – intravenous injection every 3 weeks for approx. 12 months

Are there risks?

You will be informed about possible risks or side effects associated with participation during an informed consent discussion.

Eligibility requirements

Men and women aged 18 years and older can participate in this study, with:

  • Initial diagnosis of breast cancer, without metastases except for axillary lymph node metastases
  • HER2-receptor positive tumor
  • Confirmed residual tumor in the breast or axillary lymph nodes
  • Previously completed neoadjuvant chemotherapy and immunotherapy (antibody therapy) including Trastuzumab (anti-HER2 therapy)

In addition, there are other criteria that must be met for study participation. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

Further studies by the GBG Study Group can be found here.

GeparPiPPa / GBG-105

GeparPiPPa / GBG-105

THERAPY STUDY TO EVALUATE THE POTENTIAL ADDITIONAL EFFICACY AND SAFETY OF INAVOLISIB IN THE PRE-OPERATIVE TREATMENT OF PATIENTS WITH HER2-POSITIVE, HR-POSITIVE, PIK3CA-MUTATED EARLY BREAST CANCER.

GeparPippa-GBG-105-Brustkrebsstudie

GeparPiPPa is a randomized (chance determines the treatment for each patient), non-blinded (doctor and patient know which medications are being used) Phase II study comparing pre-operative anti-hormone therapy in combination with the immunotherapeutics Trastuzumab, Pertuzumab with and without the PIK3 inhibitor Inavolisib in patients with HER2-positive, HR-positive, PIK3CA-mutated early (non-metastatic) breast cancer.

What is being investigated in this study?

The investigation of receptor status is a central aspect in the diagnosis of breast cancer. This status provides information about the presence of certain molecules in tumor cells or on their surface, which can serve as potential targets for drug treatments. One of these molecule groups is known as “HER2”. “HER2” stands for “Human Epidermal Growth Factor Receptor 2”. HER2 is a receptor on the cell surface of tumors that stimulates cell growth when activated. 20-30% of all patients with a high number of HER2 receptors (HER2 positive) on the tumor have a mutation in the PIK3CA gene. This gene is essential for the production of the enzyme PI3K, which is important for cell division, among other things. Tumors with PIK3CA mutations may have a poorer response to chemotherapy and anti-HER2 therapy. This is particularly true for breast cancer with positive hormone receptor expression (HR+). Inavolisib is an oral PI3KA inhibitor that is comparable to other drugs in the same class but is expected to have a better efficacy and tolerability profile.

What is the goal of the study?

The primary goal of the study is to compare the efficacy of therapy with Inavolisib along with concurrent endocrine therapy (anti-hormone therapy), Pertuzumab, and Trastuzumab versus endocrine therapy with Pertuzumab and Trastuzumab alone in patients with HER2-positive, HR-positive, PIK3CA-mutated early breast cancer. Additionally, the safety and tolerability of the treatment, as well as patient adherence, will be investigated.

How is the study conducted?

Breast cancer patients with a PIK3CA mutation will be randomly assigned 1:1 to one of two treatment arms and will receive:

Arm A
Anti-hormone therapy before surgery, in combination with immunotherapy (dual anti-HER2 blockade, consisting of Pertuzumab and Trastuzumab as an injection administered subcutaneously for 6 cycles (18 weeks)), combined with Inavolisib in tablet form for 6 cycles (18 weeks)

Arm B
Treatment regimen identical to Arm A, but without Inavolisib

Anti-hormone therapy consists of either Tamoxifen or an aromatase inhibitor (medication to inhibit estrogen production), possibly combined with a GnRH analog (medication to prevent ovulation) for premenopausal women and for all men. In both study arms, treatment will continue until surgery/biopsy is performed, or progressive, unacceptable side effects occur, or consent to the study is withdrawn.

Are there risks?

You will be informed about potential risks and side effects associated with participation during an informational discussion.

Participation Requirements

Men and women aged 18 and older can participate in this study, with:

  • Untreated primary breast cancer (unilateral, no metastases)
  • Breast tumor with a palpable diameter of ≥ 2 cm or an ultrasound diameter of ≥ 1 cm
  • HER2 receptor and hormone receptor positive
  • Confirmed PIK3CA mutation of the tumor

In addition, there are other criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can assess whether this study is suitable for them.

Further studies by the GBG Study Group can be found here.

New Approval for the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer

New Approval for the Treatment of Hormone Receptor-Positive, HER2-Negative Breast Cancer

Currently, the treatment of metastatic breast cancer that is hormone receptor-positive (HR+) and does not express human epidermal growth factor receptor-2 (HER2-) involves endocrine therapy (anti-hormone therapy) in combination with targeted agents, followed by mono-chemotherapy (with one agent). This treatment approach does not always provide optimal results and is often associated with a reduced quality of life. In the Phase III study “TROPiCS-02”, the antibody-drug conjugate sacituzumab govitecan was evaluated, and its efficacy and safety were compared with treatment of physician’s choice in patients with HR+ and HER2- metastatic breast cancer.

The active substance sacituzumab govitecan consists of an antibody (sacituzumab) to which a cytostatic (cell division inhibiting) substance is bound. After administration, the antibody specifically binds to a certain protein on the surface of the cancer cells. This binding ensures that the cytostatic agent detaches and is thereby activated. The thus released cytostatic then causes damage to the genetic material, leading to the death of the cancer cell.

Sacituzumab Govitecan is already approved in several countries for patients with metastatic triple-negative breast cancer who have received more than one prior systemic therapy, and in the USA for patients with pre-treated HR+/HER2- metastatic breast cancer. In the TROPiCS-02 study, patients who had been previously treated and whose metastatic breast cancer was resistant to endocrine therapy showed a clinically significant survival benefit when treated with sacituzumab govitecan, compared to the patient group receiving treatment of physician’s choice.

Based on these study results, the US Food and Drug Administration (FDA) has now also approved the antibody-drug conjugate sacituzumab govitecan (Trodelvy®) for the treatment of adult patients suffering from inoperable, locally advanced or metastatic HR+/HER2- breast cancer who have previously received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting.[/vc_column_text][/vc_column][/vc_row]

PROOFS – Registry Study

PROOFS – Registry Study

A REGISTRY STUDY FOR LONG-TERM FOLLOW-UP OF PATIENTS WITH EARLY-STAGE LUMINAL BREAST CANCER WHO ARE TREATED WITH ENDOCRINE THERAPY PLUS OVARIAN FUNCTION SUPPRESSION (OFS) OR STANDARD CHEMOTHERAPY, FOLLOWED BY ENDOCRINE THERAPY

The PROOFS registry collects real-world data on the long-term follow-up of premenopausal or perimenopausal (the year after the last menstrual period) patients with early-stage luminal breast cancer who have an intermediate to high clinical risk of recurrence and a low genomic recurrence risk, as determined by MammaPrint® (a genomic test that creates an individual tumor profile and thus provides information about the metastatic risk of breast cancer), and who are being treated or are planned to be treated with standard endocrine therapy plus ovarian function suppression (OFS) or with standard chemotherapy followed by endocrine therapy.

What is this study investigating?

For pre- and perimenopausal patients in general, there is limited data regarding optimal treatment. Currently, patients are treated with various therapies: chemotherapy + endocrine therapy (ET), ET + ovarian function suppression in premenopause, or ET with or without OFS in perimenopausal women, each based on the recommendation of the treating physician and for a duration of endocrine treatment of 5-10 years. Therefore, this registry collects current treatment data for this patient group to enable future statements about the treatment success of current standard therapies.

What is the aim of the study?

The primary objective of this study is to determine the frequency of the 5-year distant recurrence-free interval in all patients treated with (intensified) endocrine therapy alone (and with ovarian suppression in cases with increased clinical risk according to current AGO recommendations). Insights are to be gained regarding treatment with chemotherapy followed by endocrine therapy versus endocrine treatment alone. The results also aim to inform changes in the duration of endocrine treatment (especially up to 10 years for high-risk patients), as well as the introduction of intensified endocrine therapy in combination with OFS.

How is the study conducted?

In this registry study, only routine clinical data is collected – participation in the study has no influence on the patients’ treatment. Treatment is carried out independently of study participation, according to medical practice and applicable guidelines. Additional visits to the clinic/practice are not required. Data documentation begins after written consent to participate in the registry.

Initially, for example, demographic data of the patients and the status of the cancer (e.g., tumor status at initial diagnosis, genomic risk by MammaPrint®, planned/ongoing cancer treatment, quality of life) are documented. This is followed by the follow-up phase, during which the current status regarding any local recurrences or distant metastases, further cancer treatments, and patient adherence to therapy is documented at least once a year during routine follow-up visits. The follow-up phase within this registry is planned for up to 10 years after initial diagnosis (at least annual examinations in years 0-5, followed by year 7 and 10 or at the time of tumor recurrence).

Are there any risks?

You will be informed about potential risks associated with participation during an informational discussion. Since this registry is purely a documentation of clinical routine without planned additional treatment, there is no additional health risk associated with participation.

Eligibility Criteria

Women can participate in this study if they have:

  • early-stage primary breast cancer (without evidence of metastases)
  • intermediate to high clinical risk and low genomic risk of recurrence (determined by MammaPrint®)
  • pre- or perimenopausal
  • Estrogen and/or progesterone hormone receptor positive
  • HER2 receptor negative

In addition, there are further criteria that must be met for participation in the study. Interested patients should speak with the study physicians at a participating center, who can check if this study is suitable for them.

To the Study Centers