The neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved ...with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort.
Patients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization followed by 4 cycles of epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0.
Higher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%,P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3–4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline.
In HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane–epirubicin–cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.
We evaluated the pathological complete response (pCR) rate after neoadjuvant epirubicin, (E) cyclophosphamide (C) and docetaxel containing chemotherapy with and without the addition of bevacizumab in ...patients with triple-negative breast cancer (TNBC).
Patients with untreated cT1c-4d TNBC represented a stratified subset of the 1948 participants of the HER2-negative part of the GeparQuinto trial. Patients were randomized to receive four cycles EC (90/600 mg/m(2); q3w) followed by four cycles docetaxel (100 mg/m(2); q3w) each with or without bevacizumab (15 mg/kg; q3w) added to chemotherapy.
TNBC patients were randomized to chemotherapy without (n = 340) or with bevacizumab (n = 323). pCR (ypT0 ypN0, primary end point) rates were 27.9% without and 39.3% with bevacizumab (P = 0.003). According to other pCR definitions, the addition of bevacizumab increased the pCR rate from 30.9% to 41.8% (ypT0 ypN0/+; P = 0.004), 36.2% to 46.4% (ypT0/is ypN0/+; P = 0.009) and 32.9% to 43.3% (ypT0/is ypN0; P = 0.007). Bevacizumab treatment OR 1.73, 95% confidence interval (CI) 1.23-2.42; P = 0.002, lower tumor stage (OR 2.38, 95% CI 1.24-4.54; P = 0.009) and grade 3 tumors (OR 1.68, 95% CI 1.14-2.48; P = 0.009) were confirmed as independent predictors of higher pCR in multivariate logistic regression analysis.
The addition of bevacizumab to chemotherapy in TNBC significantly increases pCR rates.
Compliance and persistence are often overlooked in adjuvant breast cancer treatment.
PACT was a prospective, multicenter, randomized, open, parallel-group study assessing whether educational ...materials (EMs) enhanced compliance with aromatase inhibitor (AI) therapy in postmenopausal women with early, hormone-receptor-positive (HR+) breast cancer. The primary end points were compliance (proportion taking ≥80% anastrozole) at 12 months and persistence (proportion reporting anastrozole intake during the study period).
Four thousand eight hundred and forty-four patients were randomly assigned 1:1 to receive standard therapy or standard therapy with EMs. There was no difference between arms in compliance (N = 2740; 88.5%/88.8%, respectively, P = 0.81) or persistence rates (N = 2740; 40.5%/43.0%, respectively, P = 0.18). Modified end point analyses found no differences in compliance between arms based on the classification of: (i) patients with missing documentation or follow-up visit <9 months as non-compliant (N = 4397, P = 0.15); (ii) patients with early (≤292 days) 12-month follow-up documentation excluded (N = 4091, P = 0.19); (iii) patients reaching ≥80% compliance during individual follow-up as compliant (N = 4397, P = 0.26). Modified persistence analyses found no difference between arms (N = 4397, P = 0.37).
Addition of EMs to standard therapy did not significantly affect compliance and persistence with adjuvant anastrozole.
NCT00555867.
The purpose of this analysis was to assess the long-term impact of adding bevacizumab to adjuvant chemotherapy for early triple-negative breast cancer (TNBC).
Patients eligible for the open-label ...randomized phase III BEATRICE trial had centrally confirmed triple-negative operable primary invasive breast cancer (pT1a–pT3). Investigators selected anthracycline- and/or taxane-based chemotherapy for each patient. After definitive surgery, patients were randomized 1:1 to receive ≥4 cycles of chemotherapy alone or with 1 year of bevacizumab (5 mg/kg/week equivalent). Stratification factors were nodal status, selected chemotherapy, hormone receptor status, and type of surgery. The primary end point was invasive disease-free survival (IDFS; previously reported). Secondary outcome measures included overall survival (OS) and safety.
After 56 months’ median follow-up, 293 of 2591 randomized patients had died. There was no statistically significant difference in OS between treatment arms in either the total population (hazard ratio 0.93, 95% confidence interval CI 0.74–1.17; P = 0.52) or pre-specified subgroups. The 5-year OS rate was 88% (95% CI 86–90%) in both treatment arms. Updated IDFS results were consistent with the primary IDFS analysis. Five-year IDFS rates were 77% (95% CI 75–79%) with chemotherapy alone versus 80% (95% CI 77–82%) with bevacizumab. From 18 months after first study dose to study end, new grade ≥3 adverse events occurred in 4.6% and 4.5% of patients in the two arms, respectively.
Final OS results showed no significant benefit from bevacizumab therapy for early TNBC. Late-onset toxicities were rare in both groups. Five-year OS and IDFS rates suggest that the prognosis for patients with TNBC is better than previously thought.
NCT00528567
Trastuzumab with a taxane as first‐line therapy is now the standard of care for patients with human epidermal growth factor receptor 2 (HER‐2)‐positive metastatic breast cancer (MBC). The search for ...additional and more effective trastuzumab‐based therapies continues. Novel combinations of trastuzumab with chemotherapeutic agents, including vinorelbine, gemcitabine, and capecitabine, and hormonal therapy agents, such as tamoxifen and aromatase inhibitors, are currently under investigation in clinical trials. Available data suggest these combinations will provide additional treatment options that may ultimately lead to better outcomes for patients with HER‐2‐positive MBC. Evidence is growing for the use of trastuzumab treatment beyond disease progression and retreatment after (neo)adjuvant relapse is being explored to assist in clinical decision making. Already, the use of trastuzumab in the metastatic setting has changed HER‐2‐positive status from a marker of poor prognosis to one of better overall outcome, and ongoing studies should expand further the treatment options for patients with HER‐2‐positive MBC.
The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete ...response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses.
Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years.
Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low.
Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.
NCT 00288002, www.clinicaltrials.gov.
We carried out a prospective clinical study to evaluate the impact of the Recurrence Score (RS) on treatment decisions in early breast cancer (EBC).
A total of 379 eligible women with estrogen ...receptor positive (ER+), HER2-negative EBC and 0–3 positive lymph nodes were enrolled. Treatment recommendations, patients' decisional conflict, physicians' confidence before and after knowledge of the RS and actual treatment data were recorded.
Of the 366 assessable patients 244 were node negative (N0) and 122 node positive (N+). Treatment recommendations changed in 33% of all patients (N0 30%, N+ 39%). In 38% of all patients (N0 39%, N+ 37%) with an initial recommendation for chemoendocrine therapy, the post-RS recommendation changed to endocrine therapy, in 25% (N0 22%, N+ 39%) with an initial recommendation for endocrine therapy only to combined chemoendocrine therapy, respectively. A patients' decisional conflict score improved by 6% (P = 0.028) and physicians' confidence increased in 45% (P < 0.001) of all cases. Overall, 33% (N0 29%, N+ 38%) of fewer patients actually received chemotherapy as compared with patients recommended chemotherapy pre-test. Using the test was cost-saving versus current clinical practice.
RS-guided chemotherapy decision-making resulted in a substantial modification of adjuvant chemotherapy usage in node-negative and node-positive ER+ EBC.
Abstract
Treatment with monoclonal antibodies (mabs) has become an established component of oncological
therapy. The monoclonal antibodies available for this purpose are mainly administered
...intravenously in individually adapted doses according to body weight over longer treatment
times. For other chronic diseases such as, for example, diabetes mellitus, the subcutaneous
administration of drugs is an established therapy option. For the subcutaneous administration of
larger volumes as needed for mab solutions the extracellular matrix of the subcutaneous tissue
represents a problem. The co-formulation with recombinant human hyaluronidase makes the
relatively pain-free administration of larger fluid volumes and thus the subcutaneous
administration of monoclonal antibodies possible, as illustrated by the development of a
subcutaneous formulation of trastuzumab. This constitutes a less invasive, time-optimised and
flexible form of administration for patients with HER2-positive breast cancer that, with its
fixed dosing possibilities, contributes to therapeutic safety. The example of trastuzumab shows
that the subcutaneous administration of monoclonal antibodies can simplify oncological long-term
therapy not only for the patients but also for the medical personnel.
Zusammenfassung
Hintergrund
Der nationale und globale Anstieg von Krebserkrankungen führt zu einer Vertiefung der praktischen Präventionsmaßnahmen. Es muss aber auch eine Bewusstseinsänderung in den ...verschiedenen Bevölkerungsschichten erfolgen, um diese Maßnahme erfolgreich umsetzen zu können. Auf Bundesebene werden nationale Strategien zur Stützung der Forschung eingeleitet und umgesetzt. Zudem fördert das Präventionsgesetz die Umsetzung der praktischen Maßnahmen in den Lebenswelten der verschiedenen Zielgruppen. Die strategische Ausrichtung der Maßnahmen stützt die individuelle Entscheidung zur Krebsprävention. Als reduzierende Interaktionen werden Lebensstilfaktoren, Vorsorge- und Früherkennungsmaßnahmen gestärkt.
Material und Methoden
Diese Arbeit basiert auf einer selektiven Literaturrecherche in der Datenbank PubMed zum Thema Prävention, Früherkennung und Verhaltensänderung.
Schlussfolgerung
Die Ausrichtung der Projekte der Krebsprävention haben sich in theoretischem Ansatz und in Bezug auf die Ansprache an die Zielgruppen verändert. Um Maßnahmen passgenau verhaltens- und verhältnispräventiv auszurichten, bedarf es einer spezifischen alltagsorientierten Ansprache und damit einhergehender Stärkung von Gesundheitskompetenz und -verhalten der Bevölkerung. Die strukturellen Interventionen auf Bundesebene werden durch die Nationale Dekade gegen Krebs gebündelt.
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