Low-Intensity Adjuvant Chemotherapy for Breast Cancer in Older Women: Results From the Prospective Multicenter HOPE Trial

Abstract

PURPOSE Older women with high-risk early breast cancer (EBC) benefit from adjuvant chemotherapy, but their treatment is frequently complicated by toxic side effects, resulting in dose reductions and delays. This makes it challenging for oncologists to maintain a relative dose intensity (RDI) ≥ 85%, as recommended for optimal curative-intent treatment. Understanding which women are at risk of receiving suboptimal RDI may inform treatment discussions and guide early, targeted supportive care or geriatric comanagement interventions. METHODS This was a prespecified secondary analysis of the HOPE trial, which enrolled women age ≥ 65 years with EBC initiating neoadjuvant or adjuvant chemotherapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome was low RDI, defined as RDI < 85%. Multivariable logistic regression with stepwise selection was used to evaluate the association between baseline variables (demographic, clinical, and geriatric assessment) and low RDI. Survival probability was estimated using the Kaplan-Meier method, and the log-rank test was used to compare overall survival. RESULTS Three hundred twenty-two patients (median age at diagnosis, 70 years; range, 65-86 years) were included. The median follow-up was 4 years. Sixty-six patients (21%) had a low RDI. Age ≥ 76 years (odds ratio [OR], 2.57; 95% CI, 1.12 to 5.91; P = .03), lower performance status (OR, 4.32; 95% CI, 1.98 to 9.42; P < .001), and use of anthracycline-based or cyclophosphamide, methotrexate, and fluorouracil regimens (OR, 3.47; 95% CI, 1.71 to 7.05; P < .001) were associated with low RDI. The 5-year overall survival probability was 0.80 versus 0.91 in patients with RDI < 85 versus ≥ 85%, respectively (log-rank P = .02). CONCLUSION One in five older patients with EBC treated with standard chemotherapy received low RDI and had inferior survival outcomes. Older patients at risk for low RDI should be identified and targeted upfront before initiating chemotherapy.

Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study

“…Although trials conducted over 10 years ago had lower RDIs, including one of women randomly assigned to supervised resistance exercise versus Aerobic exercise versus UC, which found RDIs of 90%, 87%, and 84% in the three groups, respectively, our chemotherapy completion rates are similar to more recent trials. 31 Sedrak et al 31 found 80% of older patients with breast cancer received at least 85% RDI. In recent years, shorter course chemotherapy regimens have been prescribed resulting in higher RDIs.…”

Adjuvant Chemotherapy in Older Women With Early Breast Cancer

“…12 More recently, the correlation of the RDI with the survival outcomes has been reported specifically for older women with early ER-positive and HER2-negative BC, treated with various adjuvant chemotherapy regimens in the “Hurria Older PatiEnts with BC (HOPE) Study” (ClinicalTrials.gov identifier: NCT01472094). 13 HOPE is a prospective, multicenter study of patients older than 65 years with early BC, treated with standard chemotherapy, designed to comprehensively capture multidimensional geriatric, clinical, and treatment-related data. In a secondary, preplanned analysis of HOPE, the 5-year OS rate was 80% and 91% with RDI below and above 85%, respectively (multivariate hazard ratio [HR], 2.47; 95% CI, 1.20 to 5.10; P = .01).…”

“…14,15 For older women and men with BC, we prefer evidence-based treatments that have demonstrated to improve survival. On the basis of the prespecified secondary analysis of the HOPE trial, 13 TC is a preferred regimen, with primary granulocyte colony stimulating factors prophylaxis, because TC has been independently associated with RDI > 85% and better survival outcomes, as opposed to AC- and CMF-like regimens.…”

“…The value of such a clinical variable is confirmed in the secondary analysis of the HOPE trial, which identified KPS < 90% as one determinant of RDI < 85%, and of patient prognosis. 13 Accordingly, patients aged ≥ 65 years with BC should routinely be evaluated with screening oncogeriatric tools, such as the G8 and G8-modified scores. 3 The identification of potential vulnerability with screening tools commonly prompts a comprehensive evaluation, including but not limited to the KPS, that has the main aim to identify the areas of frailty and provide specific support on the basis of a precision, person-centric, and multidisciplinary support.…”

Age, Body Mass Index, Tumor Subtype, and Racial and Ethnic Disparities in Breast Cancer Survival

“…Age has also been associated with survival in patients with BC. Both younger and older age have been associated with differences in treatments and adherence as well as worse mortality . Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has also been shown to be associated with BC survival, although the role of BMI in racial and ethnic survival disparities, particularly among groups that are underreported and underrepresented in clinical trials, such as Hispanic patients, merits additional study .…”