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

Author(s): Mina S. Sedrak, MD, MS1,2; Can-Lan Sun, PhD1,3; Jingran Ji, MD2; Harvey J. Cohen, MD4; Cary P. Gross, MD5; William P. Tew, MD6; Heidi D. Klepin, MD, MS7; Tanya M. Wildes, MD, MS8; Efrat Dotan, MD9; Rachel A. Freedman, MD, MPH10; Tracey O’Connor, MD11; Selina Chow, MD12; Mary Ann Fenton, MD13; Beverly Moy, MD, MPH14; Andrew E. Chapman, DO15; William Dale, MD, PhD1,3; Vani Katheria, BS1,3; Nicole M. Kuderer, MD16; Gary H. Lyman, MD, MPH17; Allison Magnuson, DO18; and Hyman B. Muss, MD19
Source: DOI: 10.1200/JCO.22.01440 Journal of Clinical Oncology
Anjan J Patel MD

Dr. Anjan Patel's Thoughts

This study nicely confirms that older patients who are given lower doses or have treatment delays receive a lower benefit from adjuvant chemotherapy and have worse outcomes. About 20% of patients were given a low relative dose intensity overall. Of course, there may be other variables at play, but this highlights the need for early identification of patients who would benefit from aggressive supportive measures.

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.

Author Affiliations

1Center for Cancer and Aging, City of Hope, Duarte, CA 2Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA 3Department of Supportive Care Medicine, City of Hope, Duarte, CA 4Department of Medicine, Duke University School of Medicine, Durham, NC 5Department of Medicine, Yale School of Medicine, New Haven, CT 6Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 7Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC 8Department of Medical Oncology, Nebraska Medicine, Omaha, NE 9Department of Hematology Oncology, Fox Chase Cancer Center, Philadelphia, PA 10Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 11Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 12Department of Medicine, University of Chicago, Chicago, IL 13Department of Medicine, Brown University, Providence, RI 14Department of Medicine, Massachusetts General Hospital, Boston, MA 15Department of Medical Oncology, Sidney Kimmel Cancer Center/Jefferson Health, Philadelphia, PA 16Advanced Cancer Research Group, Kirkland, WA 17Department of Medicine, University of Washington, Seattle, WA 18Department of Medicine, University of Rochester Medical Center, Rochester, NY 19Department of Medicine, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC

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