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Chemotherapy Dose Intensity and Survival in Older Women With Early-Stage Breast Cancer: Analysis From the HOPE Trial


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In an analysis from the HOPE trial reported in the Journal of Clinical Oncology, Mina S. Sedrak, MD, MS, and colleagues found that approximately one-fifth of older women with early-stage breast cancer received a relative dose intensity (RDI) of neoadjuvant/adjuvant chemotherapy that was below recommended levels. Additionally, these patients had poorer survival outcome vs those with higher RDI.

As stated by the investigators, “Older women with high-risk early breast cancer 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 an 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.”

Study Details

The trial included 501 women aged ≥ 65 years with stage I to III disease enrolled between September 2011 and May 2017 who received current standard neoadjuvant/adjuvant chemotherapy regimens. The current analysis included 322 patients, excluding those with HER2-positive disease or HER2-equivocal disease who received trastuzumab and those who received nonstandard regimens, had upfront dose reduction, and who changed treatment plans after initiating therapy. RDI was calculated as the ratio of delivered to planned chemotherapy dose intensity. The primary outcome of interest was low RDI, defined as RDI < 85%.


One in five older patients with early breast cancer 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.
— Mina S. Sedrak, MD, MS, and colleagues

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Key Findings

Among the 322 patients included in the analysis, the median age at diagnosis was 70 years (range = 65–86 years). A total of 83% received chemotherapy in the adjuvant setting. Regimens included docetaxel/cyclophosphamide (TC) in 47%; anthracycline-based regimens (eg, doxorubicin/cyclophosphamide alone or followed by paclitaxel) in 47%; and cyclophosphamide, methotrexate, and fluorouracil (CMF) in 6%. A total of 85% of patients received primary granulocyte colony-stimulating factor prophylaxis with the first cycle of chemotherapy.

A total of 66 patients (21%) had RDI < 85%. In adjusted analysis, factors significantly associated with low RDI were age ≥ 76 vs 65 to 75 years (odds ratio [OR] = 2.57, 95% confidence interval [CI] = 1.12­–5.91, P = .03), physician-rated Karnofsky performance status of < 90 vs ≥ 90 (OR = 4.32, 95% CI = 1.98–9.42, P < .001), and receipt of anthracycline-based or CMF regimens vs TC (OR = 3.47, 95% CI = 1.71–7.05, P < .001).  

Median follow-up was 4.1 years (range = 63 days–8.0 years). Estimated overall survival among patients with RDI > 85% vs ≥ 85% was 91% vs 99% at 2 years and 80% vs 91% at 5 years (hazard ratio = 2.36, 95% CI = 1.14–4.87, P = .02).

The investigators concluded, “One in five older patients with early breast cancer 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.”

Dr. Sedrak, of City of Hope Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the National Institute on Aging, Breast Cancer Research Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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