Abemaciclib in Combination With Endocrine Therapy as First Line Therapy in Metastatic Breast Cancer Patients With Symp-tomatic Visceral Metastases or High Tumor Burden
Indikation (Clinical Trials):
Technische Universität München
Eli Lilly and Company
Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Frauenheilkunde
E-Mail: firstname.lastname@example.org» Kontaktdaten anzeigen
Against the above discussed background there is a clear rationale to further collect real
world data confirming that the use of endocrine based therapy in metastatic breast cancer is
beneficial for the patient cohort with symptomatic visceral metastases and high tumor burden.
Data recently presented, showed that Abemaciclib in combination with Letrozole leads to
substantial reduction in tumor size after only two cycles of therapy. Since Abemaciclib is
the only CDK4/6-inhibitor that can be given "steady state" without a "one-week-off"-period
and since there has been beginning evidence that Abemaciclib is penetrating the blood brain
barrier in patients with brain metastases, it seems reasonable to choose Abemaciclib in
combination with endocrine therapy for an observational study whose objective will be to
collect efficacy data within clinical routine on Abemaciclib in combination with endocrine
therapy within a cohort of ERpos/HER2neg breast cancer patients with symptomatic visceral
metastases or high tumor burden.
LDH-levels above 400 U/l as well as abnormal levels of breast cancer specific tumor markers
CA 15-3 and CEA have been proven to correlate with disease extent in metastatic breast cancer
and thus can be used to identify metastatic breast cancer patients with high tumor burden.
Recently it could be shown that circulating tumor DNA (ctDNA) bares greater correlation with
changes in tumor burden than CA 15-3 and can provide the earliest measure of treatment
response in women with metastatic breast cancer. This warrants further research to evaluate
ctDNA as a tool for measuring early tumor response in MBC patients.
Translational research part:
In the era of personalized cancer therapy, testing for genetic alterations has become an
essential tool in clinical practice. It allows clinicians to identify patients who are most
likely to benefit from molecularly targeted treatments. Currently, evaluation of response to
targeted drugs is largely based on imaging (CT or MRT), an approach unable to reveal
mechanistic details on individual treatment effects. Sequential biopsies of tumors and their
molecular analysis could yield additional information, but repetitive sampling of tissue that
is representative and adequate in quantity and quality is rarely feasible, especially in the
metastatic disease setting.
Liquid biopsies (LBs) represent a minimally-invasive alternative of great potential in this
setting. Although recent technical advances allow very sensitive detection of LB-based tumor
biomarkers, only few LB assays have yet entered into clinical routine.
Blood plasma samples from patients treated with Abemaciclib will be analyzed to identify
predictive cell-free (cf) DNA-based biomarkers as indicators for treatment efficacy and early
detection of resistance. To this end, cfDNA will be screened for mutations using a targeted
next-generation sequencing panel (AVENIO ctDNA Expanded Kit, Roche). This panel is covering a
total of 192 kb and consists of 77 genes, including those currently in the US National
Comprehensive Cancer Network guidelines as well as emerging biomarkers currently being
investigated in clinical trials.
For each plasma sample, concentration of cfDNA as well as presence and allelic frequencies of
tumor mutations will be measured. Additionally, associations with progression-free survival
and overall survival will be evaluated using Cox regression models. Clinical variables will
be used as covariates in multivariable regression models to evaluate the independence of the
As a result, the investigators hope to identify minimally invasive LB-based biomarkers for
serial monitoring of metastatic breast cancer patients. These biomarkers could add to the
prediction of therapy response as well as the early detection of therapy resistance towards
endocrine therapy and Abemaciclib.
1. Age ≥18 years
2. Female patients who will start endocrine therapy (aromatase inhibitor or Fulvestrant)
in combination with Abemaciclib as first line treatment for metastatic breast cancer
within clinical routine
3. Signed informed consent
4. Life expectancy greater or equal to 12 weeks
5. Histologically proven diagnosed estrogen receptor positive, HER2 negative metastatic
breast cancer not amenable to curative treatment
6. Radiographic evidence of measurable or evaluable visceral disease
7. Visceral involvement must fulfil one of the following criteria:
1. Presence of any clinical sign or symptom from visceral disease (at least one of
the following: pleural effusion, ascites, abdominal pain from liver or peritoneal
metastases, dyspnea from pleural effusion or lymphangiosis of the lung, elevated
liver enzymes (> 2x ULN), elevated bil-irubin)
2. Signs of high tumor burden (at least one of the following: LDH >399 U/l with K in
normal range, abnormal (> 2x ULN) CEA or CA15-3 level, radiographic signs of
lymphangiosis of the lung, cytologically proven bone marrow infiltration)
1. Contraindications for treatment with Abemaciclib, aromatase inhibitor or Fulvestrant
according to current SmPC
2. Prior first line therapy (endocrine or chemotherapy) for metastatic breast cancer
3. Prior treatment with any CDK4/6 inhibitor (or participation in any CDK4/6 inhibitor
clinical trial for which treatment assignment is still blinded)
4. Bone-only disease
5. Participation in clinical trials using an IMP within the last four weeks prior to
6. Treatment with a drug that has not received regulatory approval for any indication
within 28 days of initiation of study treatment for a non-myelosuppressive or
myelosuppressive agent, respectively
7. Patients who are pregnant or breast-feeding
1. objective response rate (ORR) while being on study treatment using RECIST V1.1. (Time Frame - Maximum time frame will be 48 months):
Aim of this observational study is to collect efficacy data within clinical routine on Abemaciclib in combi-nation with endocrine therapy in estrogen receptor (ER) positive, HER2 negative metastatic breast cancer patients with symptomatic visceral disease or disease with high tumor burden.
1. ORR at first, second and third time point of tumor evaluation (Time Frame - Maximum time frame will be 48 months):
ORR at first, second and third time point of tumor evaluation (according to clinical routine every 8 weeks) defined as the proportion of patients with having partial or complete response at first, second and third time point of tumor evaluation after initiation of study treatment using RECIST V1.1.
2. Disease control rate (DCR= CR+PR+SD) at first, second and third time point of tumor evaluation (Time Frame - Maximum time frame will be 48 months):
Disease control rate (DCR= CR+PR+SD) at first, second and third time point of tumor evaluation after initiation of study treatment (according to clinical routine every 8 weeks)
3. Duration of response (DoR) (Time Frame - Maximum time frame will be 48 months):
Duration of response (DoR), defined as the time from first documentation of OR to first documentation of PD according to RECISTV1.1 or death of any cause
4. Clinical response rate (CRR) at 4, 8, 16 and 24 weeks after initiation of study treatment (Time Frame - zp to 24 weeks):
Clinical response rate (CRR) at 4, 8, 16 and 24 weeks after initiation of study treatment defined as the proportion of patients assessed by the investigator as having at least one sign or symptom of clinical response.
5. Clinical benefit rate (CBR) (Time Frame - Maximum time frame will be 48 months):
Clinical benefit rate (CBR), defined as the percentage of patients with CR, PR or SD for at least 24 weeks [Time frame: initiation of study treatment to PD or death of any cause
6. Time to initial response (TTR) (Time Frame - Maximum time frame will be 48 months):
Time to initial response (TTR), defined as the time from initiation of study treatment to first documentation of objective response
7. Progression-free survival (PFS) (Time Frame - Maximum time frame will be 48 months):
Progression-free survival (PFS), defined as the time from initiation of study treatment until objective tumor progression or death, whichever occurs first
8. Time to treatment failure (TTF) (Time Frame - Maximum time frame will be 48 months):
Time to treatment failure (TTF), defined as the time from initiation of study treatment to discon-tinuation of treatment for any reason, including disease progression, treatment toxicity, and death
9. Change in tumor size (Time Frame - Maximum time frame will be 48 months):
Change in tumor size, defined as change of largest tumor-diameter on baseline tumor evaluation during the course of study treatment
10. Frequency of AE/SAE during study (Time Frame - Maximum time frame will be 48 months):
occurenec of AE/SAE during study
11. Patient reported outcomes (PRO) (Time Frame - Maximum time frame will be 48 months):
Patient reported outcomes (PRO): change from baseline to end of study in symptom burden and quality of life using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Minimum score =0 Maximum score = 100. Higher score would mean a better outcome
Abemaciclib tablets 150 mg, 100 mg, 50 mg as clinical routine: 150 mg twice daily per os, in-label administration in combination with endocrine therapy (aromatase inhibitor or Fulvestrant)
In Rheinland-Pfalz erhalten jedes Jahr über 22.000 Menschen die Diagnose Krebs. Für die Betroffenen hat dies eine hohe psychische Belastung zufolge und sie werden zudem mit vielen Fragen konfrontiert. Wichtig ist es in diesem Fall, gut informiert zu sein, beispielsweise über Therapieoptionen und Strategien zur Alltagsbewältigung.
Eine seltene Krebsart bringt nicht nur Patienten, sondern auch Ärzte an ihre Grenzen. Dabei sind seltene Krebsarten gar nicht so selten wie die Bezeichnung vermuten lässt. Rund 100.000 Menschen erkranken in Deutschland jedes Jahr an einer solchen Krebserkrankung. Im aktuellen Monatsthema stellt das ONKO-Internetportal die wichtigsten seltenen Krebsarten, die damit verbundenen Herausforderungen bei der Therapie sowie Initiativen...
Das Klinikum Herford bietet seinen gynäkologischen Krebs-Patientinnen ab sofort einen digitalen Therapiebegleiter an, der sie im Umgang mit der Erkrankung unterstützt. Die Smartphone-App MIKA begleitet Betroffene durch die Behandlung und hilft ihnen unter anderem mit Gesundheitsmonitoring und psychosozialem Coaching. Mit dem neuen digitalen Assistenten geht das Klinikum Herford einen weiteren Schritt, um Erkrankte zu mehr...
Am 18./19. Juli 2015 fand der Lauf ins Leben in Eckernförde statt. Dieser Lauf wurde dort bereits zum 11. Mal von der Schleswig-Holsteinischen Krebsgesellschaft durchgeführt. Außerdem hat die Krebsgesellschaft in den letzten Jahren bereits erfolgreiche Laufevents in anderen Städten Schleswig-Holsteins wie z.B. Flensburg, Itzehoe und Lütjenburg durchgeführt.
Warmes, sonniges Frühlingswetter: „Balsam für die Seele“ nach entbehrungsreichen Winterwochen im Pandemie-Lockdown. Neben wohltuender Wärme und sichtbarem Licht gehören allerdings auch unsichtbare ultraviolette (UV-) Strahlen zum Spektrum der Sonne. Viele Menschen unterschätzen gerade im Frühjahr die Gefahren der schon jetzt intensiven Sonnenbestrahlung. Die Deutsche Krebshilfe und die...