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Background: Eligibility criteria are a critical part of clinical trials, as they define the patient population under investigation. Besides certain patient characteristics, clinical trials often include biomarker testing for eligibility. However, patient-identification mostly relies on the trial site itself and is often a time-consuming procedure, which could result in missing out on potentially eligible patients. Pre-selection of those patients using a registry could facilitate the process of eligibility testing and increase the number of identified patients. One aim with the PRAEGNANT registry (NCT02338167) is to identify patients for therapies based on clinical and molecular data. Here, we report eligibility testing for the SHERBOC trial using the German PRAEGNANT registry.
Methods:Heregulin (HRG) has been reported to identify patients with better responses to therapy with the anti-HER3 monoclonal antibody seribantumab (MM-121). The SHERBOC trial investigated adding seribantumab (MM-121) to standard therapy in patients with advanced HER2-negative, hormone receptor–positive (HR-positive) breast cancer and HRG overexpression. The PRAEGNANT registry was used for identification and tumor testing, helping to link potential HRG positive patients to the trial. Patients enrolled in PRAEGNANT have invasive and metastatic or locally advanced, inoperable breast cancer. Patients eligible for SHERBOC were identified by using the registry. Study aims were to describe the HRG positivity rate, screening procedures, and patient characteristics associated with inclusion and exclusion criteria.
Results: Among 2769 unselected advanced breast cancer patients, 650 were HER2-negative, HR-positive and currently receiving first- or second-line treatment, thus potentially eligible for SHERBOC at the end of current treatment; 125 patients also met further clinical eligibility criteria (e.g. menopausal status, ECOG). In the first/second treatment lines, patients selected for SHERBOC based on further eligibility criteria had a more favorable prognosis than those not selected. HRG status was tested in 38 patients, 14 of whom (36.8%) proved to be HRG-positive.
Conclusion: Using a real-world breast cancer registry allowed identification of potentially eligible patients for SHERBOC focusing on patients with HER3 overexpressing, HR-positive, HER2-negative metastatic breast cancer. This approach may provide insights into differences between patients eligible or non-eligible for clinical trials.
Trial registration: Clinicaltrials, NCT02338167, Registered 14 January 2015 - retrospectively registered.
This study presents comprehensive real-world data on the use of anti-human epidermal growth factor receptor 2 (HER2) therapies in patients with HER2-positive metastatic breast cancer (MBC). Specifically, it describes therapy patterns with trastuzumab (H), pertuzumab + trastuzumab (PH), lapatinib (L), and trastuzumab emtansine (T-DM1). The PRAEGNANT study is a real-time, real-world registry for MBC patients. All therapy lines are documented. This analysis describes the utilization of anti-HER2 therapies as well as therapy sequences. Among 1936 patients in PRAEGNANT, 451 were HER2-positive (23.3%). In the analysis set (417 patients), 53% of whom were included in PRAEGNANT in the first-line setting, 241 were treated with H, 237 with PH, 85 with L, and 125 with T-DM1 during the course of their therapies. The sequence PH → T-DM1 was administered in 51 patients. Higher Eastern Cooperative Oncology Group (ECOG) scores, negative hormone receptor status, and visceral or brain metastases were associated with more frequent use of this therapy sequence. Most patients received T-DM1 after treatment with pertuzumab. Both novel therapies (PH and T-DM1) are utilized in a high proportion of HER2-positive breast cancer patients. As most patients receive T-DM1 after PH, real-world data may help to clarify whether the efficacy of this sequence is similar to that in the approval study.
Update Mammakarzinom 2018 (Teil 2) – fortgeschrittenes Mammakarzinom, Lebensqualität und Prävention
(2018)
Die Behandlung des metastasierten Mammakarzinoms hat bei immer neu zu testenden Therapien deutlich an Komplexität zugenommen. Therapien werden nunmehr nur noch für spezielle klinische oder molekulare Subgruppen entwickelt. Hierbei spielen die intrinsischen, molekularen Subtypen zwar immer noch die größte Rolle, jedoch gibt es zunehmend auch Therapien, die subgruppen- oder sogar histologieübergreifend entwickelt werden, wie z. B. der PARP-Inhibitor bei BRCA-mutierten Patientinnen (Mamma- und Ovarialkarzinom). Aber auch Supportivtherapien entwickeln sich weiter, sodass Probleme wie die Alopezie besser behandelt werden können und neue Therapiearten von Übelkeit und Erbrechen etabliert werden. In einem engen Zusammenhang mit den Supportivtherapien stehen die Nebenwirkungen, welche bei Patientinnen mit einem metastasierten Mammakarzinom einen direkten Einfluss auf die Prognose haben. Hier könnten digitale Werkzeuge helfen, um ein besseres Patientinnenmanagement zu etablieren. Diese Übersichtsarbeit soll diese Aspekte vor dem Hintergrund neuer, aktuell publizierter Studien beleuchten und einen Einblick geben, wie sich diese Studien zu etablierten Routinetherapien verhalten. Zusätzlich werden aktuelle Aspekte der Mammakarzinomprävention beleuchtet.
The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented.
In dieser Übersichtsarbeit wird dargestellt, wie neue Therapien oder neue Aspekte etablierter Therapien in Zusammenhang mit neuesten, aktuellen Erkenntnissen stehen. Neoadjuvanz, Lokaltherapie, neue Aspekte der Systemtherapie und Prognose- sowie Prädiktivfaktoren werden beleuchtet. In der Neoadjuvanz ist nach wie vor der Zusammenhang zwischen pCR und Prognose von Interesse, ebenso wie neue molekulare Prädiktoren für neue Therapien wie CDK4/6-Inhibitoren zu identifizieren. Bei der operativen Behandlung wird weiter nach einer Reduktion der Aggressivität gestrebt. Insbesondere das duktale Carcinoma in situ muss dafür noch besser verstanden werden. Bei den Systemtherapien wächst die Datenlage zum Verständnis der besten Kombinationen und Therapieabläufe für bestehende Therapieverfahren. Letztendlich muss mithilfe von Prognose- und Prädiktivfaktoren vermieden werden, dass Übertherapien stattfinden und nur die Patientin spezifische Therapien erhält, welche bei dieser individuellen Patientin eine nachgewiesene Wirksamkeit mit wenig Nebenwirkungen haben.
This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.
Uterine fibroids are the most frequent benign tumours in women of child-bearing age. Their symptoms are diverse and the quality of life of the women affected can be significantly impaired. While treatment to date has been primarily by means of surgical intervention, selective progesterone receptor modulators (SPRMs) open up new medication-based treatment options. EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recently completed its review of ESMYA® (ulipristal acetate, 5 mg), following reports of serious liver injury, including liver failure leading to transplantation in postmarketing settings. We will provide some information on the PRAC’s recommendations to minimize this risk. Nevertheless, the effectiveness and safety of the SPRM ulipristal acetate (UPA), both with regard to preoperative administration and with regard to an intermittent administration as long-term treatment for patients with symptomatic uterine fibroids, have been shown in several clinical studies (PEARL I–IV).
Adenomyosis or endometriosis genitalis interna is a frequent benign disease of women in fertile age. It causes symptoms like bleeding disorders and dysmenorrhea and seems to have a negative effect on fertility. Adenomyosis can be part of a complex genital and extragenital endometriosis but also can be found as a solitary uterine disease. While peritoneal endometriosis can be easily diagnosed by laparoscopy with subsequent biopsy, the determination of adenomyosis is difficult. In the following literature review, the diagnostic methods clinical history and symptoms, gynecological examination, 2D and 3D transvaginal ultrasound, MRI, hysteroscopy, and laparoscopy will be discussed step by step in order to evaluate their predictive value in the diagnosis of adenomyosis.
In the article titled "Selective Progesterone Receptor Modulators for the Medical Treatment of Uterine Fibroids with a Focus on Ulipristal Acetate", the affiliation of the third author was incorrect. The corrected affiliation is shown above. In addition, the Conflicts of Interest section should be updated as follows ...
The goal of this special issue is to address research concerning risks and problems related to the diagnosis and therapy of adenomyosis and myomata. During the last years, there have been several controversies in the scientific community regarding these topics. The original papers gathered in this special issue highlight and inform the readers about the innovations made in this field. ...
