Researcher and PhD Student University College London, School of Pharmacy London, United Kingdom
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 1st line to start of 2nd 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.
Discussion: Treatment delays were significantly associated with reduced PFS and occur frequently in early- stage breast cancer patients in England. Hospitals must minimise avoidable treatment delays where possible to maximise treatment efficacy in this patient cohort.
