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 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 Six versus 12 months’ adjuvant trastuzumab in patients with HER2-positive early breast cancer: the PERSEPHONE non-inferiority RCT

2020 ◽  
Vol 24 (40) ◽  
pp. 1-190 ◽  
Author(s):  
Helena Earl ◽  
Louise Hiller ◽  
Anne-Laure Vallier ◽  
Shrushma Loi ◽  
Karen McAdam ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Confidence Interval ◽  
Early Breast Cancer ◽  
Disease Free Survival ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Free Survival ◽  
Life Years ◽  
Disease Free

Background The addition of adjuvant trastuzumab to chemotherapy has significantly improved outcomes for people with human epidermal growth factor receptor 2 (HER2)-positive, early, potentially curable breast cancer. Twelve months’ trastuzumab, tested in registration trials, was adopted as standard adjuvant treatment in 2006. Subsequently, similar outcomes were demonstrated using 9 weeks of trastuzumab. Shorter durations were therefore tested for non-inferiority. Objectives To establish whether or not 6 months’ adjuvant trastuzumab is non-inferior to 12 months’ in the treatment of HER2-positive early breast cancer using a primary end point of 4-year disease-free survival. Design This was a Phase III randomised controlled non-inferiority trial. Setting The setting was 152 NHS hospitals. Participants A total of 4088 patients with HER2-positive early breast cancer who it was planned would receive both chemotherapy and trastuzumab took part. Intervention Randomisation (1 : 1) to 6 months’ or 12 months’ trastuzumab treatment. Main outcomes The primary end point was disease-free survival. The secondary end points were overall survival, cost-effectiveness and cardiac function during treatment with trastuzumab. Assuming a 4-year disease-free survival rate of 80% with 12 months’ trastuzumab, 4000 patients were required to demonstrate non-inferiority of 6 months’ trastuzumab (5% one-sided significance, 85% power), defining the non-inferiority limit as no worse than 3% below the standard arm. Costs and quality-adjusted life-years were estimated using a within-trial analysis and a lifetime decision-analytic model. Results Between 4 October 2007 and 31 July 2015, 2045 patients were randomised to 12 months’ trastuzumab and 2043 were randomised to 6 months’ trastuzumab. Sixty-nine per cent of patients had ER-positive disease; 90% received anthracyclines (49% with taxanes; 41% without taxanes); 10% received taxanes without anthracyclines; 54% received trastuzumab sequentially after chemotherapy; and 85% received adjuvant chemotherapy (58% were node negative). At 6.1 years’ median follow-up, with 389 (10%) deaths and 566 (14%) disease-free survival events, the 4-year disease-free survival rates for the 4088 patients were 89.5% (95% confidence interval 88.1% to 90.8%) in the 6-month group and 90.3% (95% confidence interval 88.9% to 91.5%) in the 12-month group (hazard ratio 1.10, 90% confidence interval 0.96 to 1.26; non-inferiority p = 0.01), demonstrating non-inferiority of 6 months’ trastuzumab. Congruent results were found for overall survival (non-inferiority p = 0.0003) and landmark analyses 6 months from starting trastuzumab [non-inferiority p = 0.03 (disease-free-survival) and p = 0.006 (overall survival)]. Six months’ trastuzumab resulted in fewer patients reporting adverse events of severe grade [365/1929 (19%) vs. 460/1935 (24%) for 12-month patients; p = 0.0003] or stopping early because of cardiotoxicity [61/1977 (3%) vs. 146/1941 (8%) for 12-month patients; p < 0.0001]. Health economic analysis showed that 6 months’ trastuzumab resulted in significantly lower lifetime costs than and similar lifetime quality-adjusted life-years to 12 months’ trastuzumab, and thus there is a high probability that 6 months’ trastuzumab is cost-effective compared with 12 months’ trastuzumab. Patient-reported experiences in the trial highlighted fatigue and aches and pains most frequently. Limitations The type of chemotherapy and timing of trastuzumab changed during the recruitment phase of the study as standard practice altered. Conclusions PERSEPHONE demonstrated that, in the treatment of HER2-positive early breast cancer, 6 months’ adjuvant trastuzumab is non-inferior to 12 months’. Six months’ treatment resulted in significantly less cardiac toxicity and fewer severe adverse events. Future work Ongoing translational work investigates patient and tumour genetic determinants of toxicity, and trastuzumab efficacy. An individual patient data meta-analysis with PHARE and other trastuzumab duration trials is planned. Trial registration Current Controlled Trials ISRCTN52968807, EudraCT 2006-007018-39 and ClinicalTrials.gov NCT00712140. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 40. See the NIHR Journals Library website for further project information.

Impact of body mass index (BMI) on the efficacy of zoledronic acid in premenopausal patients with hormone receptor positive breast cancer: An analysis of the ABCSG-12 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 514-514
Author(s):  
Georg Pfeiler ◽  
Robert Konigsberg ◽  
Christian Fesl ◽  
Brigitte Mlineritsch ◽  
Herbert Stoger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Zoledronic Acid ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Obese Patients ◽  
Free Survival ◽  
Premenopausal Patients ◽  
The Impact ◽  
Disease Free

514 Background: Zoledronic acid (ZOL) improves disease outcome in premenopausal patients with breast cancer (BC), especially in those with low estrogen environment. Obesity is associated with increased estrogen serum levels, which might influence the efficacy of ZOL. We investigated the impact of BMI on the efficacy of ZOL in premenopausal patients with BC. Methods: ABCSG-12 examined the efficacy of ovarian suppression using goserelin (3.6 mg q28d SC) in combination with anastrozole (ANA) or tamoxifen (TAM) ± ZOL 4 mg IV q6mo) in premenopausal women with endocrine-responsive BC. BMI was calculated using the prospectively collected data on patients’ height and weight at study entry. BMI definitions of the WHO were used: normal 18.5-24.9 kg/m2, overweight: BMI 25-29.9 kg/m2, obese BMI ≥ 30 kg/m2). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method and results were compared by using the log-rank test and Cox proportional hazard modeling. Results: Two thirds of the patients were normal weight (1,111) and one third was overweight (391) or obese (182). Normal weight patients treated with ZOL experienced the same benefit as overweight/obese patients treated with ZOL compared to patients without ZOL regarding disease free survival (HR 0.75, 95%CI 0.53 1.05 p = 0.09 and HR 0.71, 95%CI 0.46 1.1, p=0.12, respectively) as well as overall survival (HR 0.67, 95% CI 0.37 1.22, p=0.19 and HR 0.64, 95%CI 0.32 1.28, p=0.19, respectively). No difference regarding DFS and OS could be detected between normal weight and overweight/ obese patients treated with ZOL (HR 1.05, 95%CI 0.69 1.59, p=0.83 and HR 1.27, 95%CI 0.62 2.61, p= 0.51). Comparing normal weight patients with ZOL to obese patients with ZOL, again no difference could be observed. Conclusions: The significant outcome benefit of adjuvant zoledronic acid in ABCSG-12 can be demonstrated both in normal weight and overweight/obese premenopausal patients with early breast cancer, indicating that the bone marrow microenvironment changing impact of adjuvant bisphopshonate treatment does not correlate with patients’ BMI.

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.

Sign in / Sign up

Export Citation Format

Share Document