ADAPTcycle: Adjuvant dynamic marker-adjusted personalized therapy comparing endocrine therapy plus ribociclib versus chemotherapy in intermediate-risk HR+/HER2- early breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS596-TPS596
Author(s):  
Nadia Harbeck ◽  
Oleg Gluz ◽  
Matthias Christgen ◽  
Monika Graeser ◽  
Felix Hilpert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Intermediate Risk ◽  
Endocrine Response ◽  
Patient Reported ◽  
Disease Free

TPS596 Background: WSG (West German Study Group)-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, controlled (neo)adjuvant, non-blinded, randomized phase III trial (EudraCT 2018-003749-40). It investigates whether HR+/HER2- intermediate-risk patients (pts) (about 20 % of HR+/HER2- early breast cancer, EBC) identified during screening (OncotypeDX and 3-week endocrine therapy (ET)) derive additional benefit from 2-years of the CDK4/6 inhibitor ribociclib plus ET compared to chemotherapy (CT) (followed by adjuvant ET). Co-primary endpoints are disease-free and distant disease-free survival. Methods: Starting Q1 2019 (enrollment 36 months, 80 sites), 5600 pts will be screened and 1670 randomized in a 3:2 ratio (1002 to ribociclib + ET; 668 to standard CT followed by ET). Pre-/postmenopausal pts with histologically confirmed invasive HR+/HER2- EBC at clinically enhanced risk (cT2-4 or Ki67 > 20 % or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: Recurrence Score (RS) ≤ 25 and poor endocrine response or RS > 25 and good endocrine response in p/cN0-1 pts or RS ≤ 25 with good endocrine response in c/pN2-3 pts. Endocrine responsiveness is determined by Ki67 response (drop to ≤ 10 %) after 3-week ET. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment can be given in the neoadjuvant or adjuvant setting. 5-year follow-up consists of standard adjuvant ET. Patient reported outcomes (ePROs) are collected using CANKADO; ECG monitoring is performed using a novel CANKADO-based methodology. For translational analyses, tumor tissue will be collected at baseline (prior to ET), after 3-weeks ET (+/- 1w). Additional samples are required if residual tumor is diagnosed in case of neoadjuvant treatment and at time of recurrence. Exploratory tissue biomarker research will be conducted to assess alterations of molecular markers (e. g., ESR1, PIK3CA, CCND1, CDKN2A, RB1). Circulating DNA and tumor cells from blood samples will be used to assess mutations, gene expression, etc. Clinical trial information: 2018-003749-40.

BIG 1–98: A randomized double-blind phase III study comparing letrozole and tamoxifen given in sequence vs. alone as adjuvant endocrine therapy for postmenopausal women with receptor-positive breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA528-LBA528
Author(s):  
H. T. Mouridsen ◽  
A. Keshaviah ◽  
L. Mauriac ◽  
J. Forbes ◽  
R. Paridaens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Adjuvant Endocrine Therapy ◽  
Phase Iii ◽  
Study Entry ◽  
Second Primary ◽  
Efficacy Analysis ◽  
Disease Free

LBA528 Background: The Primary Core Analysis (PCA) of BIG 1–98 comparing letrozole (L) to tamoxifen (T) as initial adjuvant endocrine therapy showed that L significantly prolonged disease-free survival (DFS), particularly reducing the risk of relapse in distant sites, compared with T for postmenopausal women with endocrine-responsive breast cancer (BC). The aim of the Second Primary Analysis (SPA) is to compare L and T given in sequence vs. alone. On Mar 15, ‘06, the Data Safety Monitoring Committee (DSMC) will review the results of the 2nd interim analysis of the SPA. We will present safety and efficacy data from this analysis if the DSMC recommends release of the results. Methods: 8028 women were randomized upfront to Tx5 years (yrs) (A), Lx5 (B), Tx2→Lx3 (C), or Lx2→Tx3 (D); 1835 to the 2-arm option of the study (arm A vs. B; Mar ’98 - Mar ‘00) and 6193 to the 4-arm option (arm A vs. B vs. C vs. D; Apr ’99 - May ‘03). The primary endpoint was DFS (time from randomization to first occurrence of invasive BC recurrence, invasive contralateral BC, second non-breast malignancy, or death from any cause). The SPA is comprised of two pair-wise comparisons: arm A vs. C and B vs. D. Only 4-arm patients (pts) alive and disease-free at 2 yrs after study entry (corresponding to the treatment switch for arms C and D) are included. These analyses will determine if the risk of an event beyond 2 yrs is reduced by switching agents. Additional exploratory analyses based on all events and follow-up (FU) for 4-arm pts will be conducted, including the comparison of arm B vs. C. The final SPA is planned for Feb ‘08, after 662 events. In Jan ‘05, the 1st interim efficacy analysis was presented to the DSMC, after 162 events among 3641 pts (excluding those who had an event within 2 yrs or did not yet have at least 2 yrs of FU). The median SPA FU (from 2 yrs after study entry) was 11.1 months. The 2nd interim efficacy analysis will be presented to the DSMC on Mar 15, ‘06 based on data received as of a Dec 21, ‘05. Results: Conclusions: No significant financial relationships to disclose.

Palbociclib combined with endocrine treatment in breast cancer patients with high relapse risk after neoadjuvant chemotherapy: Subgroup analyses of premenopausal patients in PENELOPE-B.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 518-518
Author(s):  
Frederik Marmé ◽  
Miguel Martin ◽  
Michael Untch ◽  
Herve R. Bonnefoi ◽  
Sung-Bae Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Phase Iii ◽  
Endocrine Treatment ◽  
Hematologic Toxicity

518 Background: PENELOPE-B assessed efficacy of the CDK4/6 inhibitor 1-year palbociclib versus placebo added to endocrine therapy (ET) as post-neoadjuvant treatment in a high-risk breast cancer population. Palbociclib did not improve invasive disease-free survival (iDFS) compared to placebo (3-year iDFS 81.3% vs 77.7%) (Loibl et al. J Clin Oncol 2021). Here we report results from the subpopulation of premenopausal women. Methods: Patients with hormone receptor positive, HER2-negative breast cancer without pathological complete response after taxane‐containing neoadjuvant chemotherapy and at high risk of relapse (CPS‐EG score ≥3 or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 in a 28d cycle in addition to standard endocrine treatment including tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRH) and aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age ( < 50 vs ≥50 years), Ki-67, region, and CPS-EG score. Results: 616/1250 patients were premenopausal at the time of enrollment, 185 of these patients (30.0%) were younger than 40 years of age. 95.2% had ypN+ after surgery; 42.8% had ypT2 and 46.8% a CPS-EG score of 3. 23.1% of the premenopausal women had a Ki67 of > 15% in residual disease. 66.1% started with TAM alone; 19.3% with TAM and ovarian function suppression (OFS); and 13.6% received an AI+OFS. There was no difference in iDFS between palbociclib and placebo in the premenopausal women HR 0.948 (0.693-1.30). The 3-year iDFS was 80.6% and 78.3%, respectively. Palbociclib vs placebo in subgroups by endocrine treatment: TAM alone HR 1.05 (0.715-1.53) p = 0.817; TAM+GnRH HR 0.52 (0.267-1.02) p = 0.057 and AI+GnRH HR 1.58 (0.548-4.56) p = 0.397; pinteraction0.124. Hematologic toxicity was significantly more common with palbociclib. Non-hematological toxicity any grade palbociclib vs placebo were: fatigue 67.4% vs 51.3%; hot flushes 52.2% vs 54.8%; bone pain 15.6% vs 16.6%; and vaginal dryness 11.0% vs 11.5%. When receiving palbociclib fewer patients in the AI+GnRH group vs the TAM +/- GnRH cohort experienced anemia (54.1% vs 80.5%) and thrombocytopenia (37.8% vs 65.1%). Fatigue (75.7% vs 66.3%) and nausea (40.5% vs 24.9%) were more common with AI+GnRH than TAM +/-GnRH when palbociclib was added. Thromboembolic events were low with overall 9 events (4 vs 5; AI+GnRH 2.4% vs 1.3% TAM+/-GnRH). Conclusions: The addition of palbociclib to endocrine therapy did not improve iDFS in premenopausal women. These are the first safety results from a phase III study for the combination tamoxifen +/-GnRH and palbociclib. The addition of palbociclib to tamoxifen +/-GnRH in premenopausal women did not increase side effects compared to AI+GnRH and seems to be an alternative to AI+GnRH. Clinical trial information: NCT01864746.

The PERSEPHONE trial: Duration of trastuzumab with chemotherapy in women with HER2-positive early breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS660-TPS660
Author(s):  
Helena Margaret Earl ◽  
David A. Cameron ◽  
David Miles ◽  
Andrew M. Wardley ◽  
Emma Ogburn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Early Breast Cancer ◽  
Primary Outcome ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Disease Free

TPS660 Background: Persephone is a phase III randomised controlled trial comparing six months of trastuzumab to the standard 12 month duration in patients with HER2 positive early breast cancer in respect of disease free survival, safety and cost-effectiveness. A Persephone sister study, the PHARE trial run by the National Institute for Cancer, successfully closed to recruitment in 2010. A prospective meta-analysis is planned once each trial has reported individually. Methods: A total of 4000 patients will be randomised into each of the two treatment groups. The power calculations assume that the disease-free survival (DFS) of the standard treatment of 12 months trastuzumab will be 80% at 4 years. On this basis, with 5% 1-sided significance and 85% power, a trial randomising 2000 in each arm will have the ability to prove non-inferiority of the experimental arm defining non-inferiority as ‘no worse than 3%’ below the control arm 4 year DFS. Primary outcome is disease-free survival non-inferiority (equivalence) of 6 months trastuzumab compared with 12 months in women with early breast cancer. Secondary outcomes are overall survival non-inferiority (equivalence); expected incremental cost effectiveness; cardiology function and analysis of predictive factors for development of cardiac damage. Two mandatory sub-studies are: Tumour block collection to discover molecular predictors of survival with respect to duration of trastuzumab treatment and blood sample collection, used to discover single nucleotide polymorphisms (SNPs) as genetic/pharmaco-genetic determinants of prognosis, toxicity and treatment outcome. A third optional sub-study is the quality of life questionnaires. Results: Persephone opened to recruitment in October 2007. To date, 1847 patients (46%) of its total have been randomised from 147 UK sites. Recruitment is due to complete by December 2013 and the first planned interim analysis of the primary outcome will be mid-2016. The IDSMC last reviewed the trial in June 2011 and congratulated the Trial Management Group on the conduct of the trial and the quality of the data. No safety concerns were identified, and the IDSMC proposed that the trial continue to planned recruitment.

scholarly journals Patient-Reported Cognitive Impairment Among Women With Early Breast Cancer Randomly Assigned to Endocrine Therapy Alone Versus Chemoendocrine Therapy: Results From TAILORx

2020 ◽  
Vol 38 (17) ◽  
pp. 1875-1886 ◽  
Author(s):  
Lynne I. Wagner ◽  
Robert J. Gray ◽  
Joseph A. Sparano ◽  
Timothy J. Whelan ◽  
Sofia F. Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cognitive Impairment ◽  
Adjuvant Chemotherapy ◽  
Endocrine Therapy ◽  
Early Breast Cancer ◽  
Menopausal Status ◽  
Unique Contribution ◽  
End Point ◽  
Patient Reported ◽  
Chemoendocrine Therapy

PURPOSE Cancer-related cognitive impairment (CRCI) is common during adjuvant chemotherapy and may persist. TAILORx provided a novel opportunity to prospectively assess patient-reported cognitive impairment among women with early breast cancer who were randomly assigned to chemoendocrine therapy (CT+E) versus endocrine therapy alone (E), allowing us to quantify the unique contribution of chemotherapy to CRCI. METHODS Women with a 21-gene recurrence score of 11 to 25 enrolled in TAILORX were randomly assigned to CT+E or E. Cognitive impairment was assessed among a subgroup of 552 evaluable women using the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, administered at baseline, 3, 6, 12, 24, and 36 months. The FACT-Cog included the 20-item Perceived Cognitive Impairment (PCI) scale, our primary end point. Clinically meaningful changes were defined a priori and linear regression was used to model PCI scores on baseline PCI, treatment, and other factors. RESULTS FACT-Cog PCI scores were significantly lower, indicating more impairment, at 3, 6, 12, 24, and 36 months compared with baseline for both groups. The magnitude of PCI change scores was greater for CT+E than E at 3 months, the prespecified primary trial end point, and at 6 months, but not at 12, 24, and 36 months. Tests of an interaction between menopausal status and treatment were nonsignificant. CONCLUSION Adjuvant CT+E is associated with significantly greater CRCI compared with E at 3 and 6 months. These differences abated over time, with no significant differences observed at 12 months and beyond. These findings indicate that chemotherapy produces early, but not sustained, cognitive impairment relative to E, providing reassurance to patients and clinicians in whom adjuvant chemotherapy is indicated to reduce recurrence risk.

scholarly journals PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

2017 ◽  
Vol 3 (4) ◽  
pp. 289-303 ◽  
Author(s):  
Hiroji Iwata ◽  
Seock-Ah Im ◽  
Norikazu Masuda ◽  
Young-Hyuck Im ◽  
Kenichi Inoue ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Endocrine Therapy ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Asian Patients ◽  
Hormone Receptor Positive ◽  
Patient Reported ◽  
Epidermal Growth

Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

scholarly journals Rationale and description of a lifestyle intervention programme to achieve moderate weight loss in women with non-metastatic breast cancer: the lifestyle intervention part of the SUCCESS C Study

2020 ◽  
pp. bmjnph-2020-000119
Author(s):  
Dagmar Hauner ◽  
Brigitte Rack ◽  
Thomas Friedl ◽  
Philip Hepp ◽  
Wolfgang Janni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Lifestyle Intervention ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Phase Iii ◽  
Intervention Programme ◽  
Long Term Outcome ◽  
Free Survival ◽  
Disease Free

ObjectiveThere is growing evidence from observational studies that lifestyle factors such as obesity, an unhealthy diet and lack of physical activity are associated with poor long-term outcome in women with breast cancer. The primary objective of the lifestyle modification part of the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS C) Trial is to investigate the effect of an individualised lifestyle intervention programme aiming at moderate weight loss on disease-free survival in women with HER2/neu-negative breast cancer. Secondary objectives include the effect of the intervention on body weight, cardiovascular risk and quality of life.MethodsThe SUCCESS C Trial is an open-label, multicentre, randomised controlled phase III study using a 2×2 factorial design in women with newly diagnosed HER2/neu-negative intermediate-risk to high-risk breast cancer. The first randomisation served to compare disease-free survival in patients treated with two different chemotherapy regimens (3642 participants). The second randomisation served to compare disease-free survival in patients with a body mass index of 24–40 kg/m² (2292 participants) receiving either a telephone-based individualised lifestyle intervention programme for moderate weight loss or general recommendations for a healthy lifestyle for 2 years. Outcome analyses will be conducted after 5 years of follow-up.PerspectiveThis study will provide information on the efficacy and safety of a comprehensive lifestyle intervention programme on disease-free survival in a large cohort of women with breast cancer. EU Clinical Trials Identifier: 2008-005453-38.

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