Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer

2021 ◽  
Author(s):  
Ciara C O'Sullivan ◽  
Karla V Ballman ◽  
Linda McCall ◽  
Anuhya Kommalapati ◽  
Tyler Zemla ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Residual Disease ◽  
Disease Free Survival ◽  
The United States ◽  
Distant Recurrence ◽  
Primary Objective ◽  
Phase Iii ◽  
Her2 Positive ◽  
Free Survival ◽  
Disease Free

This report describes the rationale, purpose and design of A011801 (CompassHER2 RD), an ongoing prospective, multicenter, phase III randomized trial. Eligible patients in the United States (US) and Canada with high-risk (defined as ER-negative and/or node-positive) HER2-positive (HER2+) residual disease (RD) after a predefined course of neoadjuvant chemotherapy and HER2-directed treatment are randomized 1:1 to adjuvant T-DM1 and placebo, versus T-DM1 and tucatinib. Patients have also received adjuvant radiotherapy and/or endocrine therapy, if indicated per standard of care guidelines. The primary objective of the trial is to determine if the invasive disease-free survival (iDFS) with T-DM1 plus tucatinib is superior to iDFS with T-DM1 plus placebo; other outcomes of interest include overall survival (OS), breast cancer-free survival (BCFS), distant recurrence-free survival (DRFS), brain metastases-free survival (BMFS) and disease-free survival (DFS). Correlative biomarker, quality of life (QoL) and pharmacokinetic (PK) endpoints are also evaluated.

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.

The adjuvant use of capecitabine for residual disease following pre-operative chemotherapy for breast cancer: Challenges applying CREATE-X to a US population

2020 ◽  
pp. 107815522097175
Author(s):  
Kassidy Beyerlin ◽  
Rachel Jimenez ◽  
Mark Zangardi ◽  
Geoffrey G Fell ◽  
Christine Edmonds ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Side Effects ◽  
Residual Disease ◽  
Disease Free Survival ◽  
The United States ◽  
Free Survival ◽  
The Us ◽  
Tolerability Data ◽  
Hand Foot Syndrome ◽  
Disease Free

Introduction The CREATE-X study, conducted in Japan and South Korea, established capecitabine as an adjuvant treatment option for patients with triple negative breast cancer (TNBC) who have residual disease (RD) following neoadjuvant anthracycline or taxane-based chemotherapy. However, there are no reports on the tolerability and outcomes of adjuvant capecitabine in the US setting following publication of the CREATE-X data. Methods We retrospectively collected treatment and tolerability data from the medical records of the first 23 TNBC patients who received adjuvant capecitabine for RD post neoadjuvant chemotherapy at our institution. Disease-free survival was assessed using the Kaplan-Meier method. Results The median starting dosage of capecitabine was 1871 mg/m2/day, most commonly divided into two daily doses on days 1-14 of each 21 day cycle. 34.8% of patients completed the treatment as prescribed. Side effects associated with treatment were common with 69.6% of patients experiencing hand-foot syndrome, 39.1% of patients experiencing diarrhea, and 13.0% of patients requiring hospitalization for side effects. Of 23 patients treated with adjuvant capecitabine, 34.8% completed the planned dose, 30.4% completed with dose reduction, and 34.8% discontinued early. At a median follow-up time of 14 months, the median disease-free survival was 22 months, with 30.4% of patients experiencing recurrence. Conclusion Tolerability was poor overall compared to the CREATE-X cohort. Administering adjuvant capecitabine for TNBC patients with residual disease in the United States is challenging given differences in tolerability. More research is needed to understand how poor tolerability will affect the efficacy of this approach in the US population.

Phase III postneoadjuvant study evaluating sacituzumab govitecan, an antibody drug conjugate in primary HER2-negative breast cancer patients with high relapse risk after standard neoadjuvant treatment: SASCIA.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS602-TPS602
Author(s):  
Frederik Marmé ◽  
Elmar Stickeler ◽  
Jenny Furlanetto ◽  
Carsten Denkert ◽  
Marcus Schmidt ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Phase Iii ◽  
Nodal Involvement ◽  
Free Survival ◽  
Risk Of Recurrence ◽  
Disease Free

TPS602 Background: Women with triple-negative breast cancer (TNBC) having residual disease after neoadjuvant chemotherapy (NACT) as well as HR-positive/HER2-negative breast cancer (BC) with a CPS (clinical and post treatment pathological stage) +EG (estrogen receptor status and grade) score ≥ 3 or score 2 and nodal involvement after NACT (ypN+) are at high risk of recurrence. Sacituzumab govitecan is approved for the treatment of patients with metastatic TNBC who received at least two prior therapies for metastatic disease and has shown activity in heavily pretreated patients with metastatic HR-positive/HER2-negative BC. Therefore, sacituzumab govitecan may represent a new option against the resistant residual disease after standard NACT. Methods: SASCIA is a phase III, prospective, international, multi-center, randomized, open label, parallel group study in patients with HER2-negative BC with residual disease after NACT (NCT04595565). Eligible patients must have received taxane-based NACT for 16 weeks, including at least 6 weeks of a taxane. Patients should be at high risk of recurrence after treatment, defined as having centrally confirmed HER2-negative BC (IHC score 0-1 or FISH negative according to ASCO/CAP guideline) assessed preferably on tissue from postneoadjuvant residual invasive disease of the breast and either HR-negative (<1% positive stained cells), with any residual invasive disease > ypT1mi after NACT or HR-positive (≥1% positive stained cells), with a CPS+EG score ≥ 3 or CPS+EG score 2 and ypN+ using local ER and grade assessed on core biopsies taken before NACT. Radiotherapy should be delivered before the start of study treatment. Patients are randomized 1:1 to receive either sacituzumab govitecan 10 mg/kg body weight (days 1, 8 q3w for eight cycles) or treatment of physician´s choice (capecitabine 2000 mg/m² day 1-14 q21 or platinum-based chemotherapy i.e. carboplatin AUC 5 q3w or AUC 1.5 weekly for eight 3 weekly cycles or observation). Randomization is stratified by HR status (HR-positive vs negative) and nodal involvement after NACT (ypN+ vs ypN0). In patients with HR-positive BC, endocrine-based therapy will be administered according to local guidelines. The primary endpoint is invasive disease-free survival (iDFS). Secondary endpoints include comparison of overall survival (OS, key secondary endpoint), distant disease-free survival, locoregional recurrences-free interval, safety, compliance, iDFS and OS according to stratified and - predefined subgroups, patient reported outcome, and quality of life between treatment arms. As of February 2 2021, 7/1200 patients have been randomized in Germany. International study groups will join soon. Clinical trial information: NCT04595565.

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.

scholarly journals Adding pertuzumab to adjuvant therapy for high-risk HER2-positive early breast cancer in APHINITY: a GRADE analysis

2020 ◽  
Vol 9 (6) ◽  
pp. 423-430 ◽  
Author(s):  
Alberto Zambelli ◽  
Giovanni Pappagallo ◽  
Paolo Marchetti
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Adjuvant Therapy ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Her2 Positive ◽  
Free Survival ◽  
Distant Relapse ◽  
Disease Free

Aim: Adding pertuzumab to standard trastuzumab-based adjuvant therapy significantly improved invasive disease-free survival (IDFS) in the APHINITY trial. However, the magnitude of benefit was marginal in the overall population. Methods: We used GRADE (Grading of Recommendations Assessment, Development and Evaluation) analysis on data from APHINITY to build summary-of-findings tables to evaluate the efficacy, safety and quality of evidence of predefined clinical outcomes for the addition of pertuzumab to trastuzumab-based adjuvant therapy in patients with high-risk HER2-positive early breast cancer. Results: Pertuzumab significantly improved 3-year, event-free, absolute benefit in disease-free survival, IDFS and distant relapse-free interval (DFRI) in patients with node-positive or hormone receptor-negative disease. The analysis provides strength of evidence supporting the addition of pertuzumab in this patient population.

scholarly journals Body Mass Index and Weight Change in Patients With HER2-Positive Early Breast Cancer: Exploratory Analysis of the ALTTO BIG 2-06 Trial

2021 ◽  
Vol 19 (2) ◽  
pp. 181-189
Author(s):  
Samuel Martel ◽  
Matteo Lambertini ◽  
Dominique Agbor-Tarh ◽  
Noam F. Ponde ◽  
Andrea Gombos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Weight Loss ◽  
Early Breast Cancer ◽  
Weight Change ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Her2 Positive ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Background: The association between obesity and prognosis in HER2-positive early breast cancer remains unclear, with limited data available. This study aimed to determine the impact of body mass index (BMI) at baseline and weight change after 2 years on outcomes of patients with HER2-positive early breast cancer. Methods: ALTTO was a randomized phase III trial in patients with HER2-positive early breast cancer. BMI was collected at randomization and 2 years after. WHO BMI categories were used: underweight, <18.5 kg/m2; normal weight, 18.5 to <25 kg/m2; overweight, ≥25 to <30 kg/m2; and obese ≥30 kg/m2. A weight change from baseline of ≥5.0% and ≤5.0% was categorized as weight gain and weight loss. The impact of BMI at randomization and of weight change on disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were investigated with multivariate analyses, adjusting for baseline patients and tumor characteristics. Results: A total of 8,381 patients were included: 187 (2.2%), 3,797 (45.3%), 2,690 (32.1%), and 1,707 (20.4%) were underweight, normal weight, overweight, and obese at baseline, respectively. Compared with normal weight, being obese at randomization was associated with a significantly worse DDFS (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.04–1.50) and OS (aHR, 1.27; 95% CI, 1.01–1.60), but no significant difference in DFS (aHR, 1.14; 95% CI, 0.97–1.32). Weight loss ≥5.0% at 2 years after randomization was associated with significantly poorer DFS (aHR, 1.34; 95% CI, 1.05–1.71), DDFS (aHR, 1.46; 95% CI, 1.07–1.98), and OS (aHR, 1.83; 95% CI, 1.18–2.84). Hormone receptor and menopausal status but not anti-HER2 treatment type influenced outcomes. Toxicities were more frequent in obese patients. Conclusions: In patients with HER2-positive early breast cancer, obesity at baseline is a poor prognostic factor. Weight loss during treatment and follow-up negatively impacts clinical outcomes. Dietary counseling should be part of survivorship care programs.

scholarly journals Preoperative Systemic Therapy Versus Upfront Surgery in HER2-Positive Breast Cancer in the Real World

2021 ◽  
Vol 11 ◽  
Author(s):  
Xingfei Yu ◽  
Chen Wang ◽  
Yabing Zheng ◽  
Beibei Miao ◽  
Jiejie Hu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Real World ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Free Survival ◽  
Inverse Probability ◽  
Surgery Group ◽  
Significant Difference ◽  
Disease Free

PurposeTo compare survival in different strategies, preoperative systemic treatment versus upfront surgery, in HER2-positive early breast cancer patients in the real world.MethodsAccording to the actual upfront treatment, eligible patients from 2012 to 2015 were classified as preoperative systemic treatment or upfront surgery group prospectively. The primary endpoint is disease-free survival; the second endpoint is overall survival. All the outcomes were examined in the propensity score matching model and inverse probability of treatment weighting model.ResultsIncluded in the analysis were 1,067 patients (215 in the preoperative systemic treatment group, 852 in the upfront surgery group). In the propensity score matching model (matching at 1:1 ratio), the disease-free survival of the preoperative systemic treatment group was significantly higher than that of the upfront surgery group (hazard ratio, 0.572, 95%CI, 0.371–0.881, P, 0.012). In the inverse probability of treatment weighting model, there was no significant difference in disease-free survival between the two groups (hazard ratio, 0.946, 95%CI, 0.763–1.172, P, 0.609). For overall survival, there was no significant difference between the two groups.ConclusionThe HER2-positive patients who accepted preoperative systemic treatment had better disease-free survival than those who underwent upfront surgery by real-world statistic methods.Clinical Trial RegistrationClinicaltrials.gov, identifier NCT04249440.

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