Background: Understanding health-related quality of life (HRQOL), including side effects, is critical to guide supportive care during chemotherapy. The EA1131 trial demonstrated that Platinum (Plat) was unlikely to improve outcomes compared to capecitabine (Cape) in patients with stage II-III triple-negative breast cancer (TNBC) of basal subtype and ≥1 cm residual disease after neoadjuvant chemotherapy (NAC), supporting Cape as the continued standard of care. Patient-reported outcomes (PRO) were administered as a sub-study to understand HRQOL and symptoms from the patient’s perspective. Methods: EA1131 was amended in 9/2017 to add PRO endpoints and all patients enrolled after this amendment were eligible for the PRO sub-study. The Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (FBSI) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group Neurotoxicity Subscale (NtxS; Plat arm only) were administered at baseline (BL), cycle 3 day 1 (C3D1), and following treatment at 6 and 15 months. Due to early trial termination, the PRO sub-study target accrual (n=362) was not reached. It was hypothesized that HRQOL, assessed by the FBSI-Treatment Side Effect (TSE) subscale (range 0-16, higher score = less side effects, better HRQOL), would indicate fewer post-treatment side effects at 6 and 15 months following Plat compared to Cape. The Wilcoxon rank sum test was used to compare FBSI-TSE subscale scores and total FBSI scores (range 0-64, higher score = better overall HRQOL) between arms at BL, C3D1, 6 months and 15 months. Two-sample t-tests were used to compare change in FBSI-TSE subscale scores and total FBSI scores from BL to C3D1 between arms. Change in NtxS scores (range 0-44, higher score = less neurotoxicity) from BL to C3D1 was evaluated with the paired t-test. Analyses were exploratory and p-values <0.05 considered significant without multiple comparisons adjustment. Results: Of 331 patients eligible for the PRO sub-study (156 Plat arm, 175 Cape arm), 296 (89.4%) completed ≥1 PRO. Mean FBSI-TSE subscale scores were better for Cape at BL (Cape 14.5, Plat 13.9, p-value 0.02), for Plat at C3D1 (Cape 13.5, Plat 14.0, p-value 0.04), and did not differ at 6 months (Cape 14.6, Plat 14.7, p-value 0.70) or 15 months (Cape 14.9, Plat 14.5, p-value 0.44). FBSI-TSE subscale scores worsened from BL to C3D1 for Cape but not for Plat (mean change Cape -0.72, mean change Plat 0.15, p-value 0.003). FBSI-TSE subscale change scores from BL to C3D1 exceeded the threshold for clinically meaningful worsening (> 1.5 points) in 27% of patients on Cape and 23% of patients on Plat (p-value 0.51). Mean total FBSI scores did not differ between arms at any time (BL: Cape 50.6, Plat 49.7; C3D1: Cape 48.1, Plat 48.0; 6 months: Cape 49.9, Plat 51.1; 15 months: Cape 53.3, Plat 50.3; all p > 0.05). Mean change in total FBSI scores from BL to C3D1 did not differ between arms (Cape -2.20, Plat -1.83, p = 0.75). Mean (standard deviation) NtxS scores for the Plat arm were 38 (6.3), 36.1 (7.8), 36 (7.1) and 34.5 (7.9) at BL, C3D1, 6 months and 15 months, respectively. Mean NtxS score decreased (indicating worsening neurotoxicity) from BL to C3D1 (p-value 0.006). Conclusions: Despite more frequent severe toxicity by CTCAE criteria for Plat than Cape, patient-reported side effects worsened during treatment with Cape but not Plat. Overall, changes in HRQOL were small for both arms and resolved after therapy. However approximately one-fourth of patients had clinically meaningful worsening side effects on both arms. PRO-assessed neurotoxicity increased in the Plat arm. This PRO sub-study demonstrates that PROs capture toxicities beyond CTCAE criteria and provides novel data about patients’ experience during adjuvant chemotherapy following NAC for TNBC.

Citation Format: Karen L Smith, Fengmin Zhao, Ingrid A Mayer, Amye J Tevaarwerk, Sofia F Garcia, Carlos L Arteaga, William F Symmans, Ben H Park, Brian L Burnette, Della F Makower, Margaret Block, Kimberly A Morley, Chirag R Jani, Craig Mescher, Shabana J Dewani, Ursa Brown-Glaberman, Lisa E Flaum, Erica L Mayer, William M Sikov, Eve T Rodler, Angela M DeMichele, Joseph A Sparano, Antonio C Wolff, Kathy D Miller, Lynne I Wagner. Patient-reported outcomes in EA1131: A randomized phase III trial of platinum vs. capecitabine in patients with residual triple-negative breast cancer after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-02.