The impact of inter-cycle treatment delays on 5-year all-cause mortality in early-stage breast cancer: A retrospective cohort study.

All-cause mortality Breast Cancer Chemotherapy Delay Survival Treatment

Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
25 Aug 2024
Historique:
received: 17 05 2024
revised: 02 08 2024
accepted: 19 08 2024
medline: 1 9 2024
pubmed: 1 9 2024
entrez: 31 8 2024
Statut: aheadofprint

Résumé

Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer. This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays > 7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables. 8567 patients were included. 17 % (1448) experienced inter-cycle delay > 7 days during the treatment period. 1120 (13 %) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p < 0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95 % CI 1.12-1.61, p < 0.001). This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures.

Sections du résumé

BACKGROUND BACKGROUND
Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer.
METHODS METHODS
This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays > 7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables.
RESULTS RESULTS
8567 patients were included. 17 % (1448) experienced inter-cycle delay > 7 days during the treatment period. 1120 (13 %) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p < 0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95 % CI 1.12-1.61, p < 0.001).
CONCLUSIONS CONCLUSIONS
This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures.

Identifiants

pubmed: 39216173
pii: S0959-8049(24)00957-2
doi: 10.1016/j.ejca.2024.114301
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114301

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Authors make the following disclosures: EK: advisory board membership for AstraZeneca, Novartis, Pfizer, Roche. KM: grants from the C W Maplethorpe Fellowship, European Union Horizon 2020, the Innovation and Technology Commission of the Government of the Hong Kong Special Administration Region, the Hong Kong Research Grants Council (RGC) and personal fees from IQVIA Ltd. MDF: grant funding from CRUK, AstraZeneca, Boehringer Ingelheim, MSD and Merck, advisory board membership for Transgene; and consultancy positions for Achilles, Amgen, AstraZeneca, Bayer, Boxer, BMS, Celgene, EQRx, Guardant Health, Immutep, Ixogen, Janssen, Merck, MSD, Nanobiotix, Novartis, Oxford VacMedix, Pharmamar, Pfizer, Roche, Takeda and UltraHuman SN: reports personal fees for advisory board membership from AstraZeneca and GSK; personal fees as an invited speaker from AstraZeneca, Clovis and GSK; personal fees for Scientific Committee membership from GSK; ownership of stocks/shares of GSK; and institutional funding from AstraZeneca. RM: advisory board membership for Merck, TESARO-GSK and Clovis Oncology, speaker bureau from Roche and TESARO, and travel grants from AstraZeneca and TESARO. PC: grant funding from NIHR. All other authors declare no disclosures.

Auteurs

Luke Steventon (L)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom; UCL School of Pharmacy, Mezzanine Floor, BMA House, Tavistock Square, London WC1H 9JP, United Kingdom.

Emma Kipps (E)

The Breast Unit, The Royal Marsden NHS Foundation Trust, Fulham Road, London SW3 6JJ, United Kingdom.

Kenneth Kc Man (KK)

UCL School of Pharmacy, Mezzanine Floor, BMA House, Tavistock Square, London WC1H 9JP, United Kingdom.

Rebecca Roylance (R)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom; UCL Cancer Institute, Department of Oncology, 72 Huntley Street, London WC1 6DD, United Kingdom.

Martin D Forster (MD)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom; UCL Cancer Institute, Department of Oncology, 72 Huntley Street, London WC1 6DD, United Kingdom.

Ian Ck Wong (IC)

Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, L02-56, 2/F, Laboratory Block 21, Sassoon Road, Pokfulam, Hong Kong, China.

Michael Baser (M)

National Disease Registration Service (NDRS), NHS England, 10 S Colonnade, London E14 4PU, United Kingdom.

Rowan E Miller (RE)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom.

Shibani Nicum (S)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom; UCL Cancer Institute, Department of Oncology, 72 Huntley Street, London WC1 6DD, United Kingdom.

Samixa Shah (S)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom.

Ofran Almossawi (O)

Great Ormond Street Hospital for Children NHS Foundation Trust, Population, Policy & Practice Department, London WC1N 1LE, United Kingdom.

Pinkie Chambers (P)

Medical Oncology Department, University College London Hospitals NHS Foundation Trust, 250 Euston Road, London NW1 2PP, United Kingdom; UCL School of Pharmacy, Mezzanine Floor, BMA House, Tavistock Square, London WC1H 9JP, United Kingdom. Electronic address: p.chambers@ucl.ac.uk.

Classifications MeSH