Is adjuvant chemotherapy effective for individuals with breast cancer who are poorly represented in traditional clinical trials?
Researchers have employed real-world administrative healthcare data to retrospectively estimate the effectiveness of adjuvant chemotherapy for individuals with early-stage breast cancer who are poorly represented in clinical trials, such as those with greater comorbidities.
A previous meta-analysis of nearly 200 randomized controlled trials demonstrated that adjuvant chemotherapy – chemotherapy administered alongside another main cancer treatment with the intention of enhancing the efficacy of the main treatment – led to reduced patient mortality amongst individuals with early-stage breast cancer. However, the effectiveness of this therapeutic approach has been less well evaluated amongst individuals poorly represented in clinical trials, such as those over the age of 70, or with multiple comorbidities.
In this study, an international team of researchers from the UK and Switzerland employed real-world, administrative healthcare data, alongside econometric methods for causal analysis, to retrospectively estimate the effectiveness of adjuvant chemotherapy for individuals with early-stage breast cancer who are poorly represented in clinical trials.
For the study, researchers extracted data from the Scottish Cancer Registry – from the 2001–2015 period – on 9653 women with early-stage breast cancer who were over the age of 70, as well as 7965 women who were younger than 70 but presented with higher levels of comorbidities. High comorbidity levels were defined by individuals scoring at least one on the established Charlson Comorbidity Index, being in the top decile of inpatient stays or having at least five recorded outpatient clinic visits in the 5-year period preceding their breast cancer diagnoses.
Researchers utilized propensity score matching, and instrumental variable and Cox regression analyses to estimate hazard ratios for breast cancer-specific and all-cause mortality. These methods allowed investigators to adjust for participants’ ages, clinical prognostic factors, socioeconomic statuses and unmeasured confounding factors in their study.
Investigators observed that adjuvant chemotherapy confers a mean predicted benefit, with regards to overall survival at 10 years, of 3% for women over the age of 70 and 4% for younger women with higher levels of comorbidities.
In the study, the authors concluded: “These results support the generalizability of treatment effectiveness estimates for adjuvant chemotherapy for early breast cancer to women aged 70 years and over and those with other health conditions.”
However, the authors warned: “These results should be interpreted with appropriate caution as they are estimated from observational data and may be biased by residual confounding.”
Gray E, Marti J, Wyatt JC, Brewster DH, Hall PS, SATURNE advisory group. Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: a retrospective cohort study. PLoS Med. doi:10.1371/journal.pmed.1003006 (2019) (Epub ahead of print).