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

Author(s): Mina S. Sedrak, MD, MS^1,2; Can-Lan Sun, PhD^1,3; 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, PhD^1,3; Vani Katheria, BS^1,3; 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

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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