Abstract PD10-10: Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy
Authors: Sedrak Mina S , Sun Can-Lan , Magnuson Allison , Muss Hyman , Freedman Rachel , Gross Cary P , Tew William P , Klepin Heidi , Wildes Tanya M , Dotan Efrat , O'Connor Tracey , Cohen Harvey J , Kim Heeyoung , Katheria Vani , Jayani Reena , Arsenyan Anait , Levi Abrahm , Charles Kemeberly , Hurria Arti , Dale William 
Published: March 2020

Abstract
Background: Older adults with breast cancer receiving neo/adjuvant chemotherapy are at increased risk for toxicity and dose reductions, often leading to decreased relative dose intensity (dRDI &lt; 85%) and potentially compromised chemotherapy benefits. Identifying which older patients are projected to have dRDI with standard regimens could help to optimize systemic treatment delivery and completion.
Methods: We prospectively enrolled patients aged ≥ 65 who were starting neo/adjuvant chemotherapy for HER2-negative, stage I-III breast cancer. Geriatric assessment and clinical variables were captured at baseline. Chemotherapy regimen, dosing, and treatment-related modifications (reductions, delays, discontinuation) were also captured. RDI was calculated as the ratio of actual dose delivered to intended dose. Our primary outcome was dRDI, which we defined as RDI &lt; 85% (associated with poorer survival, Bonadonna et al. NEJM 1995). Bivariate logistic regression for dRDI was performed to elucidate the relationship with baseline factors. Stepwise regression was used to identify the significant factors that are independently associated with dRDI.
Results: Of 323 patients (median age 69, range 65-86), 216 had HR+/HER2- breast cancer and 107 had triple negative breast cancer (TNBC). Patients were treated with taxotere and cyclophosphamide [TC] (47%), anthracycline-based regimens (46%), and cyclophosphamide, methotrexate, and 5-fluorouracil [CMF] (7%). Overall, the mean RDI was 90.1% (median 100%, range 16.7%-100%), and 69 patients (21%) had dRDI (i.e. RDI &lt;85%). HR+/HER2- and TNBC had similar RDI (p = 0.74). In bivariate analysis, older age &gt; 70, higher stage (II/III), use of non-TC regimens (anthracycline-based or CMF), abnormal liver function, KPS &lt; 90, poor physical function, lack of social support, and cardiac conditions were associated with reduced RDI. Multivariate stepwise regression identified that anthracycline-based or CMF regimens (28% dRDI, OR=3.34, 95% CI 1.77-6.29), age &gt;70 (27% dRDI, OR = 2.01, 95% CI 1.11-3.63), abnormal liver function (41% dRDI, OR = 2.50, 95% CI 1.10-5.66), and KPS &lt; 90 (48% dRDI, OR = 4.31, 95% CI 2.06-9.03) were significantly associated with dRDI. dRDI was significantly associated with grade 3 or higher toxicities, hospitalization, dose reduction, dose delay, and early discontinuation of chemotherapy (all p &lt; 0.001).
Conclusion: Among older patients receiving neo/adjuvant chemotherapy for HER2-negative early-stage breast cancer, those aged &gt; 70, treated with anthracycline or CMF regimens, with abnormal liver functions, and KPS &lt; 90 were at substantially higher risk for reduced RDI (actual/planned dose) likely due to increased rates of toxicities, hospitalizations, dose modifications, and/or early treatment discontinuation. Future targeted supportive care interventions and/or alternative treatment regimens are needed to improve the delivery of chemotherapy in older patients who are predicted to have dRDI and better understand whether dRDI impacts outcomes in this population.
Citation Format: Mina S Sedrak, Can-Lan Sun, Allison Magnuson, Hyman Muss, Rachel Freedman, Cary P Gross, William P Tew, Heidi Klepin, Tanya M Wildes, Efrat Dotan, Tracey O'Connor, Harvey J Cohen, Heeyoung Kim, Vani Katheria, Reena Jayani, Anait Arsenyan, Abrahm Levi, Kemeberly Charles, Arti Hurria, William Dale. Factors associated with decreased relative dose intensity in older adults with early-stage breast cancer receiving chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD10-10.