250P - The impact of inter-cycle treatment delays on progression-free survival in early stage breast cancer

Background

Up to 30% of systemic anti-cancer therapy (SACT) treatments are reported to be delayed within cycle, due to drug toxicity, hospital capacity issues and patient choice; however, the impact on survival is unknown. This study aimed to determine the association of delays on PFS.

Methods

This population-based observational study included stage II-III breast cancer patients in England for whom guidelines recommend SACT, and who received six cycles of treatment from 01/01/2014-31/12/2015 in adjuvant and neo-adjuvant settings. Data were collected by the National Health Service as part of routine care. Cox proportional hazards model was applied to evaluate risk of progression with respect to treatment delays, adjusting for age, stage, histology, Charlson comorbidity index, ethnicity, socioeconomic group, BMI, region of England, hospital type and surgical status. Overall survival at 5 years was assessed. Delays were defined as treatment >7 days after expected date. Progression was defined as time from completion of 1^st line to start of 2^nd line SACT.

Results

8680 patients were included. 2211 (25.5%) experienced at least one delay of 7 days or more during a six-cycle drug regimen. PFS probability was significantly lower at 1, 2 and 5 years in delayed patients; 97% (CI 96.6-97.4) vs 95.8% (CI 94.9-96.6), 93.9% (CI 93.3-94.5) vs 91.6% (CI 90.5-92.8) and 86.6% (CI 85.8-87.5) vs 81.5% (CI 79.9-83.2) respectively at each timepoint in patients treated to schedule vs delayed. Cox proportional hazards analysis showed a positive association of delays >7 days with disease progression or death (HR 1.36, CI 1.19–1.55) compared to those treated to schedule. Covariates associated with reduced PFS were triple-negative histology (HR 1.63, CI 1.29-2.06) and BMI>40 (HR 1.55, CI 1.16-2.08). Non-significant associations were seen between treatment at local vs academic hospital (HR 1.15, CI 0.98-1.35), Asian (HR 0.73, CI 0.53-1.01) and Chinese (HR 0.54, CI 0.13-2.19) ethnicity compared to White ethnicity.

Conclusions

Treatment delays were significantly associated with reduced PFS and occur frequently in early-stage breast cancer patients in England. Hospitals must avoid centre-led treatment delays where possible to maximise treatment efficacy in this patient cohort.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

University College London Hospital NHS Foundation Trust.

Funding

National Institute for Health and Care Research.

Disclosure

L. Steventon: Financial Interests, Institutional, Research Grant, Award ID: NIHR201481: UK National Institute for Health and Care Research. E. Kipps: Financial Interests, Personal, Advisory Board: Pfzier, Novartis, Roche, AstraZeneca. K. Man: Financial Interests, Personal, Research Grant: UK National Institute for Health and Care Research, Hong Kong Research Grant Council, CW Maplethorpe Fellowship, European Commission Framework Horizon 2020 , Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region; Financial Interests, Personal, Funding: IQVIA Ltd . M.D. Forster: Financial Interests, Personal, Advisory Board: Bayer, EQRx, Janssen, MSD, Roche, Takeda, Transgene; Financial Interests, Personal, Research Grant: Merck, MSD. I. Wong: Financial Interests, Personal, Research Grant, Award ID: NIHR201481: UK National Institute for Health and Care Research. R. Miller: Financial Interests, Personal, Advisory Board: GSK, AZD, Merck, Shionogi, Ellipses; Financial Interests, Personal, Invited Speaker: GSK, AZD, Clovis Oncology. S. Nicum: Financial Interests, Personal, Advisory Board: GSK, AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK, AstraZeneca, Clovis; Financial Interests, Personal, Other, scientific committee: GSK; Financial Interests, Personal, Stocks/Shares: GSK; Financial Interests, Institutional, Funding: AstraZeneca. P. Chambers: Financial Interests, Personal, Research Grant, Award ID: NIHR201481: UK National Institute for Health and Care Research. All other authors have declared no conflicts of interest.