British journal of clinical pharmacology · 2026
Completion vs. early discontinuation of chemotherapy and the impact on 5-year all-cause mortality in women treated for early-stage breast cancer from 2015 to 2020: A cohort study using a target trial emulation approach.
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Steventon Luke, Ju Chengsheng, Man Kenneth K C, Roylance Rebecca, Ottaviani Diego, Creed Chiara, Sladkowski Michal, Wisner Alec, Wei Li, Chambers Pinkie
Аннотация
AIM: Chemotherapy is given for early-stage breast cancer; however, some patients discontinue before completing all planned cycles. This study investigated the impact of early chemotherapy discontinuation on treatment outcomes.
METHODS: This retrospective cohort study used a target trial emulation framework to conduct a causal analysis of the all-cause mortality impact of completing a standard course of chemotherapy. Early-stage breast cancer patients treated with chemotherapy in England between 01/01/2014 and 31/12/2015 were identified from the National Disease Registration Service and Systemic Anti-Cancer Therapy datasets. Five-year OS was estimated for patients completing greater than or equal to six chemotherapy cycles relative to discontinuing chemotherapy early (less than six cycles), representing standard treatment during the study period. A clone-censor-weight approach was used to account for time-related bias and baseline confounding. Absolute risk and hazard ratios (HRs) were calculated.
RESULTS: A total of 10 253 patients were included: 68% (n = 7014) received greater than or equal to six chemotherapy cycles, and 32% (n = 3239) received fewer than six cycles. Individuals completing greater than or equal to six cycles showed superior 5-year OS compared with discontinuation less than six cycles (absolute risk difference -1.6, 95% confidence interval [CI], -3.2, -0.1; HR 0.85, 95% CI 0.74, 0.98). Subgroup analyses showed OS benefit in patients diagnosed at stage 2 relative to Stage 3 (HR 0.82, 95% CI 0.69, 0.98), ER+/HER2+ histology (HR 0.46, 95% CI 0.24, 0.96) and Non-White ethnicity (HR 0.56, 95% CI 0.34, 0.91) when receiving six cycles.
CONCLUSION: Patients who completed greater than or equal to six cycles showed improved OS compared with those who discontinued before receiving six cycles. These findings support the identification and pre-emptive management of patients at high risk of discontinuing chemotherapy prematurely, to maximize treatment benefit.
METHODS: This retrospective cohort study used a target trial emulation framework to conduct a causal analysis of the all-cause mortality impact of completing a standard course of chemotherapy. Early-stage breast cancer patients treated with chemotherapy in England between 01/01/2014 and 31/12/2015 were identified from the National Disease Registration Service and Systemic Anti-Cancer Therapy datasets. Five-year OS was estimated for patients completing greater than or equal to six chemotherapy cycles relative to discontinuing chemotherapy early (less than six cycles), representing standard treatment during the study period. A clone-censor-weight approach was used to account for time-related bias and baseline confounding. Absolute risk and hazard ratios (HRs) were calculated.
RESULTS: A total of 10 253 patients were included: 68% (n = 7014) received greater than or equal to six chemotherapy cycles, and 32% (n = 3239) received fewer than six cycles. Individuals completing greater than or equal to six cycles showed superior 5-year OS compared with discontinuation less than six cycles (absolute risk difference -1.6, 95% confidence interval [CI], -3.2, -0.1; HR 0.85, 95% CI 0.74, 0.98). Subgroup analyses showed OS benefit in patients diagnosed at stage 2 relative to Stage 3 (HR 0.82, 95% CI 0.69, 0.98), ER+/HER2+ histology (HR 0.46, 95% CI 0.24, 0.96) and Non-White ethnicity (HR 0.56, 95% CI 0.34, 0.91) when receiving six cycles.
CONCLUSION: Patients who completed greater than or equal to six cycles showed improved OS compared with those who discontinued before receiving six cycles. These findings support the identification and pre-emptive management of patients at high risk of discontinuing chemotherapy prematurely, to maximize treatment benefit.