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Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer—Reply 

In Reply Alliance A011502, a randomized trial of aspirin 300 mg daily compared with placebo among 3020 survivors of high-risk nonmetastatic breast cancer, was terminated early due to lack of benefit from aspirin. Dr Thorat and colleagues note that for some cancers (eg, colorectal cancer) and different settings (eg, primary prevention), the time course of benefit can differ. However, in the adjuvant setting, it would still be most appropriate to use the standard stopping rules applied to adjuvant treatments such as hormonal therapy for hormone receptor–positive cancers, which, as Thorat and colleagues point out, can have a more indolent course with late recurrences. In our trial, the futility bound was crossed with a numerically worse hazard ratio for invasive disease–free survival (hazard ratio, 1.27; 95% CI, 0.99-1.63; P = .06), making it unlikely that a benefit would have been observed with further follow-up.

Aspirin vs Placebo as Adjuvant Therapy for Breast Cancer 

To the Editor The Alliance A011502 trial was stopped early for futility at a median duration of just over 1.5 years and a follow-up of less than 3 years. The mechanisms of action and optimal dose associated with aspirin’s cancer-preventive effect remain an area of active research. Trials such as Add-Aspirin and CaPP3 (ISRCTN16261285) are comparing different doses of aspirin in both the adjuvant setting and among individuals with Lynch syndrome. However, prior data make clear that aspirin’s beneficial effect on cancer incidence and mortality does not emerge until at least 5 to 10 years of follow-up and likely persists for at least 10 years after cessation of use. These unique features of aspirin’s preventive effects are particularly relevant for malignancies with a low risk of early events and deaths, such as hormone receptor–positive breast cancer, in which the annual hazards of recurrence are low but remain stable during a prolonged period, up to 20 years. The eligibility criteria of this trial were revised according to this rationale. Almost 90% of the participants in the Alliance A011502 trial were women with hormone receptor–positive breast cancer. Therefore, the number of events accrued at the early-stoppage decision likely represented only a fraction of events that would be expected in the long term. In this context, we suggest that the futility therefore should not have been based on typical statistical criteria but rather should have also considered the unique pharmacology of aspirin and the natural history of breast cancer, for which longer follow-up, as originally planned, would have been more informative.

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer 

1. The 5-year OS rate for pembrolizumab vs placebo was 86.1% vs 81.7% with HR 0.51 (significant). 2. Immune-mediated adverse events grade 3 or higher occurred in 13.0% with pembrolizumab vs 1.5% with placebo. Evidence Rating Level: 1 (Excellent) Study Rundown: Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks key therapeutic targets, leading
The post Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer first appeared on 2 Minute Medicine. Source: 2 Minute Medicine

#VisualAbstract: Pembrolizumab Increases Survival in Early-Stage Triple-Negative Breast Cancer 

Click here to read this study in NEJM. ©2024 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.
The post #VisualAbstract: Pembrolizumab Increases Survival in Early-Stage Triple-Negative Breast Cancer first appeared on 2 Minute Medicine. Source: 2 Minute Medicine

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