Comorbidity Associated With Shorter Overall Survival but Not With Time to Relapse or Toxicity in Older Women on Adjuvant Chemotherapy

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In the Cancer and Leukemia Group B (CALGB) 70103 study, comorbidity was associated with shorter overall survival among older women with early-stage breast cancer and good functional status receiving adjuvant chemotherapy. “The presence of four or more conditions appeared to be a threshold for shorter survival in this cohort,” Heidi D. Klepin, MD, MS, of Wake Forest School of Medicine, Winston-Salem, North Carolina, and colleagues reported in the Journal of Oncology Practice. Comorbidity was not associated with toxicity or time to relapse.

CALGB 70103

CALGB 70103 is a quality-of-life companion study to the CALGB 49907 (Alliance) trial, which found that women aged ≥ 65 years old treated with standard adjuvant chemotherapy (either doxorubicin/cyclophosphamide or cyclophosphamide/methotrexate/fluorouracil [5-FU]) had a lower risk of breast cancer recurrence and death than those treated with capecitabine.

For the companion study, investigators collected survey data regarding comorbidity, social support, stressful life events, toxicity, physical function, adherence, and neurobehavioral symptoms before, during, and after completion of adjuvant therapy. The 329 participants also completed the Physical Health Subscale of the Older American Resources and Services Questionnaire. Slightly more than half of the patients (171) had received standard chemotherapy, 99 with doxorubicin/cyclophosphamide and 72 with cyclophosphamide/methotrexate/5-FU], and 158 patient had received capecitabine. The median age of the patients was 71 (range, 65–89), and most patients (68%) had stage II disease.

Comorbidity Burden

The older Americans 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,” the investigators explained. With these data, the researchers then evaluated associations among comorbidity, toxicity, time to relapse, and overall survival.

The number of comorbidities ranged from 0 to 10 (median 2) and the comorbidity burden score ranged from 0 to 25 (median 3). The most common conditions were arthritis, occurring in 58% of patients, and hypertension, affecting 55%. At least one grade 3 to 5 adverse event occurred in 52% of patients, with the total number of events ranging from 0 to 28. “Of these, 28% were hematologic, 12% gastrointestinal, and 3% neurologic. Only one person died of treatment-related toxicity,” the researchers wrote. At a median 5.2-years follow-up, the overall mortality rate was 25%, and the breast cancer–specific mortality rate was 11%. Sixteen percent of patients relapsed during follow-up.

After adjusting for age, tumor size, treatment, node, and receptor status, the risk of death increased by 18% for each comorbidity (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.06–1.33). There was a similar association between comorbidity burden and overall survival (HR =1.08, 95% CI = 1.03–1.14). Comorbidity burden does adversely affect life expectancy and “should be included in treatment decision-making regarding expected benefit of adjuvant therapy,” the authors concluded.

Klepin HD et al: J Oncol Pract 10:e285-e292, 2014.