scholarly journals Prognostic role of distant disease-free interval from completion of adjuvant trastuzumab in HER2-positive early breast cancer: analysis from the ALTTO (BIG 2-06) trial

ESMO Open ◽  
2020 ◽  
Vol 5 (6) ◽  
pp. e000979
Author(s):  
Matteo Lambertini ◽  
Dominique Agbor-Tarh ◽  
Otto Metzger-Filho ◽  
Noam F Ponde ◽  
Francesca Poggio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
First Line ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Distant Disease ◽  
Free Interval ◽  
Group A ◽  
Group B ◽  
Disease Free

BackgroundIn HER2-positive breast cancer, time elapsed between completion of (neo)adjuvant trastuzumab and diagnosis of metastatic disease (‘trastuzumab-free interval’, TFI) is crucial to choose the optimal first-line treatment. Nevertheless, there is no clear evidence to support its possible prognostic role.MethodsIn the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) trial, patients with HER2-positive early breast cancer were randomised to 1 year of either trastuzumab alone, lapatinib alone, their sequence or their combination. This exploratory analysis included only patients in the trastuzumab alone or trastuzumab plus lapatinib arms who developed a distant disease-free survival (DDFS) event. Overall survival (OS) was defined as time between date of DDFS event and death; age at diagnosis, tumour size and hormone receptor status were the variables included in the multivariate models.ResultsOut of 8381 patients included in ALTTO, 404 patients in the trastuzumab alone and trastuzumab plus lapatinib arms developed a DDFS event, of which 201 occurred <12 months (group A) and 203 >12 months (group B) after completion of adjuvant trastuzumab. No significant difference in location of first DDFS event was observed (p=0.073); a numerically higher number of patients in group A than in group B developed brain metastasis (26% vs 15%). Choice of first-line therapy differed between the two groups (p=0.022): in group A, more patients received lapatinib (25% vs 11%) and less pertuzumab (8% vs 17%). Median OS was 29.3 and 18.4 months in groups B and A, respectively (adjusted HR 0.69; 95% CI 0.54–0.89; p=0.004). The longer OS for patients in group B was observed across the analysed subgroups without interaction according to hormone receptor status (p=0.814) nor type of administered adjuvant anti-HER2 treatment (p=0.233).ConclusionsTFI has prognostic value in patients with HER2-positive early breast cancer treated with adjuvant trastuzumab-based therapy. TFI is a valid tool to better individualise clinical recommendations and to design future first-line treatment trials for metastatic patients.

Prognostic analysis according to the expression of hormone receptors in HER2-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11075-e11075
Author(s):  
Inmaculada Gallego Jimenez ◽  
David Morales Pancorbo ◽  
Jose Fuentes Pradera ◽  
Javier Salvador ◽  
Juan L. Bayo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Hormone Receptor ◽  
Hormone Receptors ◽  
Cerebral Disease ◽  
Disease Free Interval ◽  
Free Interval ◽  
Group A ◽  
Group B ◽  
Disease Free

e11075 Background: Overexpression HER 2 + + + is a distinct group within the breast cancer with different treatments in both the adjuvant and advanced setting. However, from the clinical point of view, there are significant differences within this group HER2 + + + referred to response to trastuzumab, metastatic sites and survival intervals. Recently reported data guides to a worse prognosis in the subgroup expressing hormone receptors. We propose to study these differences in HER2 + + + between subgroups hormone receptor positive and negative. Methods: Retrospective observational study of all patients diagnosed with HER2 + + + at the Hospital Virgen de Valme between the years 2005-2011. We studied the disease-free interval (DFS) and global survival (OS). We also studied the frequency of brain metastases and cerebral disease-free interval (BDFS). We explore differences between the hormone receptor-negative groups (group A) and positive (group B). All patients have been treated with at least one line of trastuzumab. Results: N = 73 (40 group A and 33 group B). Median age was 58 and 55 respectively. 33 patients had metastases in the course of the disease. 7 patients initially diagnosed with metastatic stage. There is a difference of 5.0 months in group A favorable DFS (p = 0.28). The OS was 52 months in group A versus 48 months in group B (difference of 4 months p = 0.18). The BDFS was 57 months for group A and 15 months for group B (p = 0.1). The incidence of brain metastases was 27% versus 9%. Conclusions: Our data suggests a better prognosis in terms of DFS, OS and BDFS in hormone receptor-negative group. Likewise, the incidence of brain metastases was three times lower. We need well design clinical trials, monitoring and therapeutic strategies for this subgroup of patients.

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.

One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis

2018 ◽  
Vol 173 (2) ◽  
pp. 247-254 ◽  
Author(s):  
Alessandro Inno ◽  
Sandro Barni ◽  
Antonio Ghidini ◽  
Alberto Zaniboni ◽  
Fausto Petrelli
Keyword(s):  
Breast Cancer ◽  
Systematic Review ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
One Year

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients

2015 ◽  
Vol 11 (10) ◽  
pp. 1493-1500 ◽  
Author(s):  
G Mustacchi ◽  
F Puglisi ◽  
AM Molino ◽  
D Crivellari ◽  
C Ghiotto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Observational Study ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

Cost-effectiveness of six months versus 1-year adjuvant trastuzumab in HER2 positive early breast cancer in Egypt

2020 ◽  
Vol 23 (6) ◽  
pp. 575-580
Author(s):  
Gihan Hamdy Elsisi ◽  
Yousery Nada ◽  
Noha Rashad ◽  
João Carapinha ◽  
Ahmad O. Noor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Early Breast Cancer ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab

Trastuzumab emtansine: a game changer in HER2-positive early breast cancer

2020 ◽  
Vol 16 (32) ◽  
pp. 2595-2609
Author(s):  
Max S Mano
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Pathological Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Trastuzumab Emtansine ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Epidermal Growth ◽  
Game Changer

Trastuzumab emtansine (T-DM1), given postoperatively for 14 cycles to patients with human epidermal growth factor receptor 2-positive (HER2-positive) early breast cancer (EBC) who failed to achieve a pathological complete response after standard chemotherapy and HER2 blockade, represents probably the greatest progress in the management of this aggressive form of breast cancer since the adjuvant trastuzumab pivotal trials. This article addresses the rationale behind the conception of the KATHERINE trial, T-DM1’s structure and pharmacokinetics data, clinical efficacy data of the KATHERINE trial and of other EBC trials with T-DM1, safety aspects, implications of the KATHERINE trial results to clinical practice and future perspectives in the management of HER2-positive EBC.

Sign in / Sign up

Export Citation Format

Share Document