Author Archives: Robert Hickmann

Breast Cancer Study Showed Improved Progression-Free Survival in Advanced HR+, HER2- Breast Cancer

A new Phase III breast cancer study, led by Dr. Kümmel, shows promising results for the treatment of advanced HR+, HER2- breast cancer. The so-called postMONARCH study is the first of its kind to investigate the benefit of “treatment beyond progression” with CDK4/6 inhibitors. Patients whose disease had progressed despite prior therapy with CDK4/6 inhibitors and endocrine therapy benefited from continued treatment with abemaciclib. The study recorded a 27% risk reduction for disease progression and demonstrated a significant improvement in progression-free survival (PFS)

Study Design and Results

Study Lead: Dr. Kümmel

Design: Randomized, placebo-controlled Phase III study

Treatment: Abemaciclib

Results:

Abemaciclib showed a significant improvement in progression-free survival (PFS).
There was a 27% risk reduction for disease progression.
The control arm performed better than expected, but the results confirmed the benefit of continued CDK4/6 inhibitor therapy.

This study shows for the first time that continued treatment with CDK4/6 inhibitors after disease progression can be beneficial.

Epik-B5

EPIK-B5 Study

This study can enroll adult men and postmenopausal women with advanced HR-positive, HER2-negative breast cancer with a PIK3CA mutation

Breast cancer has various classifications, including by stage or growth rate. For treatment, it is important to determine whether certain proteins (receptors) are present on the tumor’s surface. This is referred to as hormone receptor status (estrogen and progesterone) and HER2 status. Treatment consists of various therapies. For example, surgery is often performed, supplemented by chemotherapy or radiation. Individualized hormone therapy can also be administered, adapted to the hormone receptor status.

What is being investigated in this study?

BYL719 – Investigational Drug: inhibits the activity of the protein PI3K (phosphatidylinositol-3-kinase), thereby influencing a specific signaling pathway. Changes in the PIK3CA gene (a gene that influences the PI3K protein) or the PTEN protein (phosphatase and tensin homolog) are responsible for the PI3K signaling pathway always being active. It is suspected that the activation of this pathway contributes to the onset and growth of tumors.

Fulvestrant – Standard Treatment: blocks the effect of the hormone estrogen in the body. This limits the promotion of tumor growth by estrogen.

What is the aim of the study?

The purpose of the study is to find out whether BYL719 in combination with the already approved active substance Fulvestrant is safe, well-tolerated, and effective.

How is the study conducted?

As part of the study, all participants receive Fulvestrant, either in combination with BYL719 or with a placebo (medication without active substance).
The probability of receiving BYL719 is 50% (1:1 chance).

The study is divided into the following sections:
Screening: a detailed check is performed to determine if the study is suitable for interested participants. During the screening, a molecular pre-examination to determine the PIK3CA mutation status also takes place. This phase can last up to 4 weeks.

Treatment Phase: If all participation requirements are met, patients are randomly assigned (randomization) to 2 treatment groups:

Group 1: receives the investigational drug BYL719
Group 2: receives a dummy drug (placebo)

The study takes place in treatment cycles of 28 days each. All participants receive Fulvestrant as an intramuscular injection on Day 1 and 15 of the first cycle, and on Day 1 of subsequent cycles. The study medication corresponding to the group, BYL719 or placebo, is taken by participants at home as a capsule.

Follow-up Phase: the health status of the participants continues to be observed, without medication being administered.

Are there risks?

Side effects may occur during study treatment. These can vary from person to person. Therefore, the health of study participants is closely monitored throughout the entire study. Those interested in participating should discuss the risks of study participation with the study physician beforehand. This allows them to make a well-informed, personal assessment of all advantages and disadvantages.

Eligibility Criteria

Eligibility includes:

for postmenopausal women
for adult men who are sterilized or use condoms for contraception
with diagnosed locally advanced or metastatic breast cancer
patients must have already undergone prior therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor

The study physician at a study center will provide information on the exact participation requirements, nature, significance, risks, and scope of the study. The study physician decides whether individual participation in the study is medically possible. This decision is made based on all medical specifications, which are precisely defined for each study.

This study is commissioned and financed by:

Prof. Kümmel – Methadone for Cancer?

Change from July 1 – Mammography Screening also for Women Aged 70-75

From July 1, 2024, the mammography screening program for early detection of breast cancer will be extended to women aged 70 to 75. Previously, the program was limited to women between 50 and 69 years of age. From this date, women can register for an appointment with the responsible central offices if their last examination was at least 22 months ago. A personal invitation is not yet being sent.

Further information can be found on the G-BA website.

What is a mammography screening?

SURVIVE Breast Cancer Study with Prof. Janni

Prof. Janni from Ulm University Hospital presented the SURVIVE study to us at the Post-ASCO, the 25th NOGGO Gynecological Oncology Update in Berlin. It summarized the most important and latest developments in gynecological cancer medicine that were discussed this year at the American Society of Clinical Oncology (ASCO) conference in Chicago, USA.

Zur SURVIVE-Studie

Merck’s Phase 3 Study Shows Success in Breast Cancer Treatment

Merck’s Phase 3 Study Shows Success in Breast Cancer Treatment

Merck announced that the Phase 3 KEYNOTE-522 study of Keytruda (anti-PD-1 therapy) met its overall survival endpoint in high-risk early-stage triple-negative breast cancer (TNBC). In combination with chemotherapy as a pre-operative treatment and subsequent monotherapy after surgery, Keytruda showed significant improvement compared to chemotherapy alone. No new safety concerns were identified. This is the first time an immunotherapy-based treatment has shown a survival benefit in TNBC patients.

More information…

TROPION-Breast04

TROPION-Breast04 Study

Therapy with antibody-drug conjugate and immunotherapy or standard therapy in previously untreated patients with early-stage triple-negative breast cancer

TROPION-Breast04 is a randomized (treatment assignment for the specific patient is by chance), controlled, Phase 3 therapy study. The study compares a new therapy against the current standard treatment and is aimed at patients with triple-negative (or hormone receptor-low, “HR-low”/ HER2-negative), early (Stage II or III) breast cancer. Furthermore, these patients have not yet received any treatment (treatment-naive).

What is being investigated in this study?

Datopotamab deruxtecan (Dato-DXd) is a drug consisting of two parts: Datopotamab (an antibody) and deruxtecan (a cancer drug), which are linked together. Datopotamab binds to a protein called Trophoblast Cell Surface Antigen 2 (TROP2), which is found on TNBC tumors. TNBC stands for “triple negative breast cancer”. This means that the breast cancer cells do not have receptors (protein compounds on the cell nucleus or cell membrane) for estrogen, progesterone, and HER2. Once bound, Dato-DXd is taken up into the tumor cell, where Deruxtecan is released to kill the tumor. Durvalumab is a drug that blocks the activity of a protein called PD-L1, making tumors more susceptible to being killed by the body’s own immune cells.

In previous studies with patients with TNBC who were treated with Dato-DXd alone (TROPION-PanTumor01) or in combination with Durvalumab (BEGONIA study), efficacy against breast cancer was observed.

What is the objective of the study?

The study targets patients with triple-negative breast cancer (TNBC), a type of breast cancer where the cells lack HER2, estrogen, or progesterone receptors. The current standard treatment for patients with TNBC is initial treatment with Pembrolizumab, combined with chemotherapy, followed by the removal of the tumor and lymph nodes from the armpit. Pembrolizumab is continued for a total of one year after surgery. Despite this highly effective tumor treatment, not all patients are cured. Therefore, this treatment needs to be improved so that more patients with TNBC can be cured.

Therefore, the TROPION-Breast04 study will investigate whether Dato-DXd combined with Durvalumab, followed by surgery and continued Durvalumab, is more effective than the current standard treatment for these patients. The study will evaluate how well Dato-DXd plus Durvalumab works and describe the side effects.

How is the study conducted?

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

Arm 1:
Before surgery (neoadjuvant):
Datopotamab deruxtecan together with Durvalumab as an intravenous infusion every 3 weeks for 8 cycles (infusions)
After surgery (adjuvant):
Durvalumab as an intravenous injection every 3 weeks for 9 cycles

Arm 2:
Before surgery (neoadjuvant):
Pembrolizumab as an intravenous infusion every 3 weeks together with Carboplatin and Paclitaxel for 4 cycles. Subsequently, Pembrolizumab and Cyclophosphamide and Doxorubicin or Epirubicin as an intravenous infusion every 3 weeks for 4 cycles
After surgery (adjuvant):
Pembrolizumab as an intravenous infusion every 3 weeks for 9 cycles

Are there any 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 years or older can participate in this study, with:

Triple-negative or HR-low & HER2-negative breast cancer without metastases
Stage II-III
No evidence of distant metastases
Previously untreated (no therapy started yet, e.g., surgery, radiotherapy, systemic therapy, immunotherapy, etc.)

In addition, there are further criteria that must be met for participation in the study. Interested patients should speak with the investigators at a study center, who can check if 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:

TROPION-Breast03 (Recruitment Completed)

TROPION-Breast03 Study

Antibody-drug conjugate therapy with or without immunotherapy in patients with triple-negative and early breast cancer and residual tumor in the breast or axilla after neoadjuvant chemotherapy and completed surgery

Study recruitment was completed in November 2024.

TROPION-Breast03 is an open-label, randomized (treatment assignment for the specific patient is by chance), controlled, Phase 3 therapeutic study. The study compares three different therapies and is aimed at patients with triple-negative (tumor cells have no estrogen, no progesterone, and no HER2 receptors), early (Stage I-III) breast cancer. In these patients, drug therapy was administered before surgery, and after surgery, residual tumor was found in the breast and/or axillary lymph nodes.

Triple-negative breast cancer is a type of breast cancer where the tumor cells have no estrogen or progesterone receptors in their nucleus and no HER2 receptors on their surface. Neoadjuvant chemotherapy is administered before the planned surgery. After neoadjuvant chemotherapy, the breast cancer and additional lymph nodes from the axilla are removed. If tumor cells are still detected in the removed tumor tissue, there is a high probability that tumor cells remain in the patient’s body and the breast cancer will recur. This necessitates further treatments.

What is being investigated in this study?

In patients with triple-negative breast cancer, the active substance Datopotamab deruxtecan (Dato-DXd) already showed efficacy against breast cancer in a previous study. Dato-DXd is an antibody-drug conjugate, i.e., a cancer drug linked to an antibody. Datopotamab deruxtecan binds to a protein called TROP2 located on cancer cells and is thereby taken up into the cancer cells, where the cancer drug is released and kills the cancer cells.

What is the aim of the study?

The TROPION-Breast03 study is designed for patients who underwent surgery after completing medicinal, neoadjuvant therapy and in whom residual tumor was detected despite treatment (in the breast or axillary lymph nodes). Patients with residual tumor generally have a higher risk of disease recurrence. The study investigates whether treatment with Dato-DXd in combination with the immunotherapy Durvalumab offers an advantage over the current, effective standard treatment (therapy choice by treating physicians).

Currently, there is no information available on whether all three treatments are equally effective or if one of the treatments is more effective than the others. To eliminate this uncertainty and to be able to provide patients with the most effective treatment in the future, studies like this TROPION-Breast03 study are being conducted.

What is the study procedure?

Within the scope of the study, there are three treatment options (“arms”) to which patients are randomly assigned in a 2:1:2 ratio:

Arm 1:
Datopotamab deruxtecan as an intravenous infusion every 3 weeks for 8 cycles (infusions) together with Durvalumab intravenous injection every 3 weeks for 9 cycles

Arm 2:
Datopotamab deruxtecan as an intravenous infusion every 3 weeks for 8 cycles

Arm 3:
Current therapy according to guidelines and at the discretion of treating physicians (Capecitabine and/or Pembrolizumab)

Are there any risks?

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

Eligibility criteria

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

triple-negative breast cancer, Stage I-III
Confirmed residual tumor in the breast or axillary lymph nodes
No mutation in BRCA1/2 genes (detection in patient’s blood cells)
Prior surgery and previously completed neoadjuvant therapy with anthracycline +/- taxane +/- carboplatin +/- pembrolizumab
Previously completed radiation therapy (if applicable)

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:

ADAPTlate – Study

ADAPTlate Study

Personalized therapy study in patients with hormone receptor-positive, HER2 receptor-negative early-stage breast cancer who have a clinically or genomically high risk of late recurrence

The ADAPTlate is a randomized, controlled, open-label, personalized Phase 3 therapy study adapted to dynamic tumor markers, targeting pre- and postmenopausal women with HR-positive and HER2-negative early-stage breast cancer who have a clinically or genomically high risk of late recurrence (late recurrence of the disease). This study compares the efficacy and safety of therapy with Abemaciclib plus standard endocrine therapy versus standard endocrine therapy alone after surgery.

Patients with intermediate clinical risk and unknown genomic risk can also be included and will receive genomic testing within the study. Furthermore, patients with isolated locoregional recurrence (re-occurrence of the tumor in the same breast or its vicinity) with a high-risk profile can participate in ADAPTlate.

What is being investigated in this study?

Patients with a high risk of recurrence are currently treated as standard with chemotherapy plus endocrine therapy (ET). However, this patient group cannot always optimally benefit from standard endocrine therapy. Furthermore, the tumor often develops resistance to ET at the time of recurrence. The ADAPTlate study aims to investigate whether patients derive additional benefit from treatment with Abemaciclib in combination with ET compared to ET alone.

Abemaciclib belongs to the so-called cyclin-dependent kinase inhibitors or CDK 4/6 inhibitors. Cyclin-dependent kinases are proteins that are significantly involved in cell cycle control and are often overactive in tumor cells. Inhibition of these proteins can lead to a reduction in tumor growth. Abemaciclib has been approved as a drug since September 2018 for women with hormone receptor-positive breast cancer that has metastasized or is locally advanced. In 2022, the combination therapy of Abemaciclib and ET was approved for women with HR-positive, HER2-negative, node-positive early-stage breast cancer with a high risk of recurrence.

What is the aim of the study?

The overarching goal of the study is to improve decision-making for individualized, tumor-specific treatment of early breast carcinomas. Specifically, the study examines the invasive disease-free survival of patients treated with Abemaciclib + ET compared to the control group treated with standard ET. Additionally, the study also investigates the quality of life of patients in both treatment arms.

What is the study procedure?

The study comprises two phases:

Phase 1:
2-year treatment phase in one of the two treatment arms

– Abemaciclib + endocrine therapy
– Standardized endocrine therapy according to clinical guidelines

Phase 2:
Follow-up phase of at least 1 year with standard ET for up to a maximum of 5.5 years

Are there any risks?

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

Eligibility Requirements

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

Primary early-stage breast cancer (without distant metastases) or
locoregional recurrence (re-occurrence of the tumor in the same breast) with a high-risk profile
Intermediate to high clinical or high genomic risk of breast cancer recurrence
(Post)menopausal or premenopausal status
Estrogen and/or progesterone hormone receptor positive
HER2 receptor negative
Initial diagnosis no more than 6 years ago

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 check if this study is suitable for them.

More about ADAPTlate: