Frederik Marmé

• MD, PhD
• Sektionsleiter Translationale Gynäkologische Onkologie at Heidelberg University

Background: The randomized, open-label phase 3 TROPiCS-02 study demonstrated that sacituzumab govitecan (SG) was associated with significantly improved overall survival (OS) and progression-free survival (PFS) vs chemotherapy for patients with previously treated hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–...

Background: Nearly 30% of HR+ early breast cancer (eBC) patients (pts) treated with neoadjuvant chemotherapy (NACT) and surgery will experience BC recurrence, many with incurable distant metastatic disease. There is currently no blood-based biomarker that can identify pts with residual disease and at high risk of recurrence before and during adjuva...

Background: Axillary nodal status is an important prognostic factor in breast cancer (BC), guiding (neo)adjuvant systemic treatment and postoperative radiotherapy. As axillary surgery does not significantly affect BC mortality itself, it is considered as a staging procedure in clinically node-negative patients. The replacement of axillary lymph nod...

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis. The current first-line treatment for advanced TNBC (aTNBC) is determined by the expression of programmed cell death-ligand 1 (PD-L1). In the ATRACTIB trial—a multicenter, single-arm, phase 2 study—we evaluated the combination of atezolizumab, p...

5538 Background: Therapeutic cancer vaccines combined with immune checkpoint inhibitors offer a promising strategy to enhance anti-tumor responses. We recently demonstrated the safety and clinical efficacy of VB10.16, a DNA-based therapeutic cancer vaccine encoding HPV16 E6/E7 oncoproteins fused to CCL3L1 for antigen-presenting cell targeting, in H...

Background Progression-free survival (PFS) for patients with metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) breast cancer significantly improved with cyclin-dependent kinase 4/6 inhibitors as part of first-line treatment. No data is available for these patients on how the risk of progression ev...

This review summarizes the latest developments for the treatment of patients with early-stage breast cancer. Most of the clinically relevant changes were the result of using immune checkpoint inhibitors to treat patients with triple-negative breast cancer (TNBC) and CDK4/6 inhibitors to treat patients with hormone receptor-positive, HER2-negative (...

The use of CDK4/6 inhibitors, the new PI3K/AKT-kinase inhibitors, selective estrogen receptor-degraders (SERDs), antibody-drug conjugates, immune therapies and PARP inhibitors in recent years has resulted in a marked change in the therapy landscape for patients with advanced stage breast cancer. CDK4/6 inhibitors, trastuzumab deruxtecan, and sacitu...

Breast cancer diagnosed during pregnancy (PrBC) is a rare occurrence but may become more prevalent as women nowadays tend to postpone childbearing until later in life. Further understanding of how pregnancy affects the tumor microenvironment (TME) is essential. We constructed Tissue Microarrays (TMA) of tumor specimens from 126 pregnant breast canc...

Medical advancements in breast cancer are truly remarkable. Especially in recent years, numerous new therapeutics have been approved and surgical strategies have been de-escalated for specific patient groups. In the therapeutic setting, CDK4/6 inhibitors as oral maintenance therapy in early breast cancer and immune checkpoint inhibitors (Pembrolizu...

Background SG is approved in pretreated HR+/HER2- mBC based on the TROPiCS-02 study (NCT03901339). Mutations in specific genes may affect efficacy of SG, including PIK3CA/TP53 (common in BC, may impact outcomes) and TACSTD2/TOP1 (may confer resistance to Trop-2-directed ADCs like SG). We assessed specific mutations at BSL and EOT in TROPiCS-02 to i...

PURPOSE The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746 ) recruited patients with hormone receptor+/human epidermal growth factor receptor 2– early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 1...

In TROPiCS-02, sacituzumab govitecan (SG) demonstrated significantly longer overall survival and progression-free survival with improved quality of life vs. chemotherapy treatment of physician’s choice (TPC) in patients with HR+/HER2− metastatic breast cancer (mBC). The safety profile was consistent with previous studies of SG. We assessed the bene...

Importance Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose-limiting adverse effect of taxane-based chemotherapies. Currently, there is no established strategy for prevention or treatment. Objective To compare the effectiveness of 1-sided hand cooling and compression for preventing CIPN in patients with primary breast cancer rec...

Plain Language Summary What is this summary about? This is a summary about the TROPiCS-02 trial, which was a study of a drug called sacituzumab govitecan (brand name: TRODELVY®) used for the treatment of breast cancer. The most common type of breast cancer is called HR-positive/HER2-negative breast cancer. HR-positive means the cancer cells have re...

Objectives The German quality assurance program (QS-Ovar) representatively documents treatment and survival for patients with first diagnosis of primary ovarian cancer in the third quarters of 2004, 2008, 2012, 2016, and 2021. We evaluate lymphadenectomy (LNE) rates in dependence on histologic subtype and outcome for early ovarian cancer FIGO I. Me...

PURPOSE To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC). METHODS Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We...

Background Second-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cance...

Background and Objectives Dose-dense anthracycline-based chemotherapy has emerged as a critical strategy in managing high-risk breast cancer, offering survival benefits through increased dose intensity or shortened intervals. While short-term studies report preserved left ventricular ejection fraction (LVEF), the long-term cardiotoxicity of such re...

Purpose The randomized GeparOLA trial reported comparable pathologic complete response (pCR) rates with neoadjuvant treatment containing olaparib versus carboplatin. In this study, we evaluate the association between functional homologous recombination deficiency (HRD) by RAD51 foci and pCR and the potential of improving patient selection by combin...

Background In PAOLA-1/ENGOT-ov25, the addition of olaparib to bevacizumab maintenance improved overall survival in patients with newly diagnosed advanced ovarian cancer. We describe the safety profile and quality of life (QoL) of this combination in older patients in PAOLA-1. Methods Safety (CTCAE v4.03) and QoL (EORTC QoL Questionnaires Core 30 a...

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expressi...

Zielsetzung: QS-Ovar dokumentierte 2004/2008/2012/2016 und 2021 alle Ovarialkarzinomerstdiagnosen (OC) im 3. Quartal. Diese repräsentative Datenerhebung evaluiert Therapiestandardumsetzung und Outcome für FIGO I Ovarialkarzinome. Materialien/Methoden: Die Therapiequalität orientierte sich an gültigen Therapiestandards und Leitlinien. OP-Qualität wu...

Background Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies. Methods On-treatment biopsies from 297 patients with invasive B...

Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ri...

GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients ( n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-base...

Background Treatment of elderly ovarian cancer (OC) patients follows a fine line between risk and benefit and is often below recommended standards. The German quality assurance program QS Ovar provides a deep and representative insight into the treatment of elderly OC patients and their outcome during the past decade. Methods All German hospitals w...

Background Recent and detailed data regarding treatment quality of patients with AOC in the era of precision medicine are largely unknown in Germany. Methods All German hospitals treating patients with ovarian cancer were asked to document prospectively all patients with first diagnosis in the third quarter in 2021. Details of tumor, treatment and...

LBA5501 Background: Paclitaxel or pegylated liposomal doxorubicin (PLD) in combination with bevacizumab (bev) are standard treatment options in patients with relapsed ovarian cancer not candidates for platinum, but responses are usually short-lived. Recently, two trials have reported a numerical but non-significant advantage from the addition of at...

Purpose The PI3K signaling pathway is frequently dysregulated in breast cancer, and mutations in PIK3CA are relevant for therapy resistance in HER2-positive (HER2pos) breast cancer. Mutations in exons 9 or 20 may have different impacts on response to neoadjuvant chemotherapy-based treatment regimens. Experimental Design We investigated PIK3CA muta...

566 Background: The concept of intrinsic subtyping has been an important step for understanding of breast cancer (BC) as a heterogenous disease. However, these subtypes are not adapted to therapy-induced molecular plasticity. We have evaluated a high-risk luminal BC clinical trial cohort to identify new additional adaptive BC subtypes based on mole...

1075 Background: In the phase 3 TROPiCS-02 study, SG, a Trop-2–directed antibody-drug conjugate coupled to SN-38 as the payload, demonstrated clinically meaningful improvement in survival outcomes over chemotherapy in patients (pts) with pretreated HR+/HER2- mBC. SN-38 leads to double-stranded DNA damage, therefore we hypothesized that in tumors wi...

Background The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. Patients and methods Patients with hormone re...

Background The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study. Methods First-line endocrine-sensitive, hormone receptor-pos...

3029 Background: SG is an antibody-drug conjugate targeted to Trop-2 that received approval for treatment of previously treated metastatic triple negative breast cancer (mTNBC) and HR+/HER2- mBC in multiple countries and accelerated approval for previously treated metastatic urothelial cancer (mUC) in the US. In multiple clinical trials, SG has dem...

e17542 Background: Maintenance monotherapy with PARP-inhibitor (PARPi), olaparib has previously shown good effectiveness and tolerability in total population of patients with PSROC who were in response to platinum-based chemotherapy (PBC) in the C-PATROL study. Here we present the overall survival (OS) data in different subgroups. Methods: The pros...

Background Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies. Methods On-treatment biopsies from 297 patients with invasive B...

Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore,...

Background The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician’s choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2−) metastatic breast cancer (mBC). Here, we present health-related qu...

Background: Despite recent advances in personalized medicine, conventional chemotherapy remains a backbone in breast cancer therapy. Thus, identifying markers predicting sensitivity or resistance to individual chemotherapeutics is of great importance. Methods: In the EpiTax neoadjuvant trial, enrolling patients between 1997-2003, patients with prim...

BACKGROUND Triple-negative breast cancer (TNBC) is an aggressive tumor characterized by poor outcomes and new treatment strategies are urgently required. The programmed cell death-ligand 1 (PD-L1) antibody (Ab) atezolizumab (ATZ) combined with first-line (1L) nab-paclitaxel (nab-PTX) is approved in multiple countries for the treatment of PD-L1-posi...

Background: In the PENELOPEB trial, the addition of 1-year of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib to standard endocrine therapy (ET) for women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer at high risk of recurrence after neoadjuvant chemotherapy (NACT) did...

Background Sacituzumab govitecan (SG) is a Trop-2directed antibody-drug conjugate approved for second-line or later (2L+) treatment of metastatic triple-negative breast cancer in multiple countries and for 2L+ treatment of HR+/HER2‒ (IHC 0, 1+, or 2+/ISH) metastatic breast cancer (mBC) in the US. SG significantly improved progression-free surviva...

[This corrects the article DOI: 10.1055/a-2238-3153.].

The PHERGain trial investigated the potential of metabolic imaging to identify candidates for chemotherapy deescalation in human epidermal growth factor receptor 2 (HER2)-positive, invasive, operable breast cancer with at least 1 breast lesion evaluable by [18F]FDG PET/CT. [18F]FDG PET/CT responders were defined as patients with an SUVmax reduction...

Introduction/Background AGO-OVAR 2.21 is the first phase III trial in recurrent ovarian cancer that compared two bevacizumab-containing combination chemotherapy regimens independent of prior anti-angiogenic therapy. As safety and efficacy data on bevacizumab re-challenge is limited, this present exploratory analysis focuses on patients with prior a...

Introduction/Background Immune checkpoint inhibitors have generally shown disappointing results in phase 3 trials in ovarian cancer and their role in combination with standard therapy is unclear; however, subgroup analyses have yielded unexpected results. We explored clinical outcomes according to investigator-selected chemotherapy in the ANITA (NC...

Introduction/Background The standard therapy for advanced/recurrent endometrial cancer includes carboplatin and paclitaxel (CP). Robust biological rationale suggested a synergy between immunotherapy and chemotherapy in this setting. Methodology AtTEnd is an academic study in advanced or recurrent endometrial carcinoma/carcinosarcoma patients with...

Molecular factors play a crucial role in the development of targeted therapies for metastatic breast cancer. This study aimed to explore new specific and targeted therapies for metastatic breast cancer. The latest findings on treatment of metastatic breast cancer with antibody–drug conjugates (ADC) are presented. Prolonged progression-free survival...

Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice. Therefore,...

What is this summary about? Sacituzumab govitecan (brand name: TRODELVY ® ) is a new treatment for certain types of advanced or metastatic breast cancer. One common type of breast cancer has at least 1 of 2 hormone receptors (HR positive) and does not have human epidermal growth factor 2 (HER2 negative). The HR and HER2 receptors are known to influ...

Purpose Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor–positive, HER2-negative metastatic...

Introduction/Background Primary results from the ENGOT-OV16/NOVA study showed that niraparib maintenance therapy significantly prolonged progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PSROC) regardless of germline BRCA (gBRCA) mutation or homologous recombination deficiency (HRD) biomarker status. Here...

Background: Sacituzumab govitecan demonstrated significant progression-free survival benefit over chemotherapy in the phase 3 TROPiCS-02 trial in patients with pretreated, endocrine-resistant hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+ and HER2-) metastatic breast cancer with limited treatment options. Here, w...

Purpose Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubi...

TPS5618 Background: Besides PARP inhibitors and bevacizumab, there are no approved maintenance therapies after platinum based chemotherapy for patients with a platinum sensitive relapsed epithelial ovarian cancer (OC). Immune checkpoint inhibitors (ICI) as single agents have limited activity in OC. One attractive strategy is to turn OC from immunog...