Disease-free (DFS) and overall survival (OS) at 3.4 years (yrs) for neoadjuvant bevacizumab (Bev) added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC), for women with HER2 negative early breast cancer: The ARTemis trial.

Earl, Helena; Hiller, Louise; Dunn, Janet A.; Blenkinsop, Clare; Grybowicz, Louise; Vallier, Anne-Laure; Abraham, Jean; Hughes-Davies, Luke; McAdam, Karen; Chan, Stephen Y.; Ahmad, Rizvana; Hickish, Tamas; Houston, Stephen; Rea, Daniel; Bartlett, John M.S.; Caldas, Carlos; Cameron, David; Provenzano, Elena; Thomas, Jeremy; Hayward, Larry

doi:10.1200/jco.2016.34.15_suppl.1014

Cited by 7 publications

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“…In this analysis our study confirms this in both the 12-and the 6-month arms (OR 1.69, 95% CI 1.27 to 2.25, and OR 1.76, 1.27 to 2.43, respectively). Our previous publication on the first 2500 patients 73 suggested that the cardiac effects of more than three cycles of anthracyclines were not seen when 6 months of trastuzumab was given. However, this analysis, which includes all patients and limits cardiac effects to the quantifiable LVEF, does not confirm any differential effect between 6 and 12 months.…”

Section: Discussionmentioning

confidence: 99%

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

Earl

Hiller

Vallier

et al. 2020

Health Technol Assess

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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.

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Section: Discussionmentioning

confidence: 99%

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

Earl

Hiller

Vallier

et al. 2020

Health Technol Assess

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“…The primary endpoint analysis had already been published and a significantly higher pCR rate was observed when bevacizumab was added to neoadjuvant chemotherapy (22% vs. 17%, p = 0.03) [9]. As shown at this year's ASCO Annual Meeting, this difference did not translate into superior outcomes in terms of DFS and OS [10]. In patients receiving chemotherapy alone, pCR predicted a favorable long-term outcome (pCR 97% vs. non-pCR 76%, p = 0.0006) while no such correlation was seen in the bevacizumab group (pCR 84% vs. non-pCR 74%, p = 0.19).…”

Section: Neoadjuvant Therapymentioning

confidence: 94%

ASCO 2015: Highlights in breast cancer

Bartsch

Bergen

2015

memo

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“…Bevacizumab lost its FDA approval for the treatment for metastatic breast cancer in 2010 over safety concerns outweighing the possible PFS benefits 54 . In recent years, bevacizumab showed an improved response rate in combination with carboplatin 55 as well as in combination with etoposide and cisplatin in patients progressing post-WBRT 56 , although the response rate was not associated with OS/PFS improvements as shown in the ARTemis trial 57 .…”

Section: Srsmentioning

confidence: 97%

Brain Metastases: A Modern Multidisciplinary Approach

O'Halloran

Gutiérrez

Kalyvas

et al. 2020

Can. J. Neurol. Sci.

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Brain metastases (BM) are the most common intracranial neoplasm and represent a major clinical challenge across many medical disciplines. The incidence of BM is increasing, largely due to improvements in primary disease therapeutics conferring greater systemic control, and advancements in neuroimaging techniques and availability leading to earlier diagnosis. In recent years, the landscape of BM treatment has changed significantly with the advent of personalized targeted chemotherapies and immunotherapy, the adoption of focal radiotherapy (RT) for higher intracranial disease burden, and the implementation of new surgical strategies. The increasing permutations of options available for the treatment of patients diagnosed with BM necessitate coordinated care by a multidisciplinary team. This review discusses the current treatment regimens for BM as well as examines the salient features of a modern multidisciplinary approach.

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Disease-free (DFS) and overall survival (OS) at 3.4 years (yrs) for neoadjuvant bevacizumab (Bev) added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC), for women with HER2 negative early breast cancer: The ARTemis trial.

Cited by 7 publications

References 0 publications

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

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

ASCO 2015: Highlights in breast cancer

Brain Metastases: A Modern Multidisciplinary Approach

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