Comorbidity, Chemotherapy Toxicity, and Outcomes Among Older Women Receiving Adjuvant Chemotherapy for Breast Cancer on a Clinical Trial: CALGB 49907 and CALGB 361004 (Alliance)

Abstract

Purpose: We evaluated associations among comorbidity, toxicity, time to relapse (TTR), and overall survival (OS) in older women with early-stage breast cancer receiving adjuvant chemotherapy. Cancer and Leukemia Group B 49907 (Alliance) randomly assigned women Ն 65 years old with stages I-III breast cancer to standard adjuvant chemotherapy or capecitabine. We reviewed data from 329 women who participated in the quality of life companion study CALGB 70103 and completed the Physical Health Subscale of the Older American Resources and Services Questionnaire. This questionnaire captures data on 14 comorbid conditions and the degree to which each interferes with daily activities. A comorbidity burden score was computed by multiplying the total number of conditions by each condition's level of interference with function. Outcomes were grade 3 to 5 toxicity, TTR, and OS. Logistic regression was used to evaluate associations between comorbidity and toxicity, and Cox proportional hazards models for TTR and survival. Methods:Results: Number of comorbidities ranged from 0 to 10 (median 2); the comorbidity burden score ranged from 0 to 25 (median 3). The most common conditions were arthritis (58%) and hypertension (55%). Comorbidity was associated with shorter OS, but not with toxicity or TTR. The hazard of death increased by 18% for each comorbidity (hazard ratio [HR] ϭ 1.18, 95% CI ϭ 1.06 to 1.33) after adjusting for age, tumor size, treatment, node and receptor status. Comorbidity burden score was similarly associated with OS (HR ϭ 1.08; 95% CI, 1.03 to 1.14). Conclusions:Among older women enrolled onto a clinical trial, comorbidity was associated with shorter OS, but not toxicity or relapse.

Adjuvant chemotherapy in elderly patients with primary breast cancer: are women ≥65 undertreated?

“…Similar results were reported by Klepin et al (2014), who showed that both chemotherapy tolerance and DFS were not negatively affected by comorbidity. However, when interpreting the data published by Klepin et al, it should be noted that patients in their study had an excellent performance status.…”

Comorbidities and Their Management: Potential Impact on Breast Cancer Outcomes

“…As a result, there are limited data available on the impact of comorbidities on treatment complications among breast cancer patients and the underlying reasons for failure to complete treatment. A recent study, for instance, that evaluated the impact of self-reported comorbidities among older women receiving adjuvant chemotherapy for breast cancer while in the CALGB 49907 and CALGB 361004 clinical trials found comorbidity to be associated with shorter overall survival, but not with toxicity or time to relapse (Klepin et al 2014 ), possibly because these women all had good functional status with less severe comorbidity at the time of enrollment since eligible patients could not have a medical condition that would make the protocol hazardous (Klepin et al 2014 ). Greater understanding of the degree to which various comorbidities affect breast cancer treatment and ultimately breast cancer survival is a research priority, and can be addressed through both observational studies as well as randomized trials designed to more broadly examine the potential impact of new breast cancer treatments across the entire targeted patient population.…”

Comorbidity in older adults with cancer

“…(23, 24) Similarly, in a recent secondary analysis of comorbidity in older adults with breast cancer, no association with toxicity was found. (25) In a study evaluating chemotherapy related hospitalizations, severe comorbid illness (CCI score ≥3) increased the risk of hospitalization nearly 10 fold and was the strongest predictor of hospitalization. (21) Moreover, patients with comorbidities are less likely to complete chemotherapy compared to patients without comorbidity.…”