Abstract P2-13-02: Patient-reported outcomes with trastuzumab monotherapy versus trastuzumab plus standard chemotherapy as a postoperative adjuvant therapy in HER2-positive elderly breast cancer patients (RESPECT): A randomized, open-label, phase 3 clinical trial
Authors: Kobayashi K , Taira N , Sawaki M , Sagawa N , Baba S , Saito T , Kawahara T , Hagiwara Y , Uemura Y , Shimozuma K , Ohashi Y , Mukai H 
Published: May 2019

Abstract
OBJECTIVE: The RESPECT trial compared 1-year trastuzumab monotherapy with trastuzumab plus standard chemotherapy as a postoperative adjuvant therapy in HER2-positive elderly breast cancer patients. Primary objective of this study was to verify the noninferiority of 1-year trastuzumab monotherapy to trastuzumab plus chemotherapy in terms of disease free survival, and the planned analysis showed that the difference of restricted mean survival time between two groups at 3 years was 0.45 months (reported by Sawaki at ASCO2018). This report assesses the patients-reported outcomes and health-related quality of life (HRQoL).
PATIENTS AND METHODS: The study was done at 99 hospitals in Japan. Elderly women (70 to 80 years old) with HER2-positive, stageI-IIIA invasive breast cancer treated by surgery with clear resection margins were randomly assigned to receive either 1-year trastuzumab or 1-year trastuzumab plus standard chemotherapy, stratified by age, hormone-receptor status, pathological lymph node metastasis and institution. Patients completed questionnaires at baseline, 2 months, 1year, and 3 years after protocol treatment started. The primary outcome was global HRQoL assessed using Functional Assessment of Cancer Therapy-General (FACT-G) total score, and secondary outcomes were chemotherapy-induced peripheral neuropathy (CIPN), instrumental activities of daily living (IADL), anxiety, depression, and subjective happiness. We did the analyses by intention to treat, including patients who completed questionnaires at baseline before start of protocol treatment, and 5point or more change is meaningful in FACT-G total score. This study is registered with ClinicalTrials.gov, NCT01104935.
RESULTS: Between Oct 2009 and Oct 2014, 275 patients were enrolled in the study, of whom 9 patients were excluded: 135 assigned to trastuzumab monotherapy and 131 assigned to trastuzumab plus chemotherapy. We detected significant difference between treatment groups for: clinically meaningful HRQoL deterioration rate at 2 months (31% for trastuzumab monotherapy vs 48% for trastuzumab plus chemotherapy; p=0.016) and at 1year (19% vs 38%; p=0.009), clinically meaningful HRQoL improvement rate at 2 months (38% for trastuzumab monotherapy vs 15% for trastuzumab plus chemotherapy; p&lt;0.01) and at 1year (43% vs 25%; p=0.021), severe sensory CIPN rate at 2months (1.9% for trastuzumab monotherapy vs 14.4% for trastuzumab plus chemotherapy; p=0.001), IADL score at 1year (11.97 for trastuzumab monotherapy vs 11.54 for trastuzumab plus chemotherapy; p&lt;0.042), Hospital Anxiety and Depression Scale score at 2months (8.92 for trastuzumab monotherapy vs 10.79 for trastuzumab plus chemotherapy; p&lt;0.003), and subjective happiness score at 1year (12.8 for trastuzumab monotherapy vs 11.8 for trastuzumab plus chemotherapy; p&lt;0.024).
CONCLUSION: Given the small advantage of adjuvant trastuzumab plus chemotherapy compared to trastuzumab monotherapy for elderly HER-2 positive breast cancer women, decisions about treatment should be informed by the risk for adverse health effects associated with chemotherapy.
Citation Format: Kobayashi K, Taira N, Sawaki M, Sagawa N, Baba S, Saito T, Kawahara T, Hagiwara Y, Uemura Y, Shimozuma K, Ohashi Y, Mukai H. Patient-reported outcomes with trastuzumab monotherapy versus trastuzumab plus standard chemotherapy as a postoperative adjuvant therapy in HER2-positive elderly breast cancer patients (RESPECT): A randomized, open-label, phase 3 clinical trial [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-13-02.