Patient-reported outcomes in N1 breast cancer: A phase III trial comparing whole-breast to whole-breast plus regional irradiation after taxane-based chemotherapy (KROG 1701)

Abstract

Background: Recent randomized trials have highlighted the benefits of regional node irradiation (RNI) in high-risk node-positive or pN1 breast cancer, yet its impact in the context of modern taxane-based adjuvant chemotherapy remains unclear. In this multi-center phase III trial, we study to prove the hypothesis that there is no difference in terms of disease-free survival between standard whole-breast irradiation (WBI) with RNI and WBI alone in pN1 breast cancer patients receiving taxane-based adjuvant chemotherapy. Comprehensive patient-reported outcomes (PROs) collected at multiple time points are now reported. Methods: The KROG 17-01 trial (NCT03269981), a prospective, multicenter, non-inferiority study, randomized patients with pN1 breast cancer after breast-conserving surgery and adjuvant taxanecontaining chemotherapy to WBI or WBI+RNI. Both conventional and hypofractionated radiotherapy (RT) were allowed. PROs were assessed using the EORTC QLQ-C30 and QLQ-BR23 modules. All data were collected at baseline, during RT, and at follow-up intervals of 3-6 months, 1, 2, 3, 4, and 5 years post-treatment. Linear mixed models were used to compare PROs between treatment arms. Results: From April 2017 to December 2021, 840 patients were enrolled; 777 received intervention as assigned, and 750 completed baseline PRO questionnaires (387 in WBI+RNI, 363 in WBI). Overall, PRO domains improved over time (p,0.001). During RT, the WBI+RNI group experienced more fatigue, nausea, and vomiting (p,0.05), and reported lower global health (p=0.090) and physical functioning (p=0.049) with borderline significance compared to the WBI group. At 3-6 months post-RT, WBI+RNI group also showed higher arm symptom scores (p=0.030). Apart from these specific timepoints, no significant differences were observed in other PRO domain scores, including arm and breast symptoms, between treatment arms. In addition, there was no significant differences in PRO domains according to RT techniques and fractionation, except for breast symptoms during RT, favoring hypofractionation and intensity-modulated RT. Conclusions: In patients with pN1 breast cancer treated with taxane-based adjuvant chemotherapy, adding RNI was associated with minor, transient declines in specific PRO domains. However, these differences were not clinically significant, indicating comparable overall patient experiences between the two treatment arms. Clinical trial information: NCT03269981. Research Sponsor: National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea; HA17C0043010018. © (2024), (Lippincott Williams and Wilkins). All rights reserved.