Adjuvant capecitabine and trastuzumab for stage IA HER2-positive breast cancer (IRIS-A): A phase II clinical trial.

508 Background: Weekly paclitaxel and trastuzumab represents a standard option for most stage I human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC)s based on results of the single arm phase II APT trial. However, the protocol-induced toxicity was not absent, prompting interest in better tolerated approaches that retain high clinical efficacy. The series of “IRIS” study including cohort A(2020, capecitabine and trastuzumab), B(2020, endocrine therapy and trastuzumab), C (2021, short-period capecitabine and trastuzumab) and D (2021, vinorelbine and trastuzumab) were designed as single arm trials regarding de-escaltion of adjuvant therapy without intravenous chemotherapy in early-stage HER2+ BCs. Herein we reported the results of IRIS-A, a single-group, phase II study to determine whether treatment with capecitabine and trastuzumab was well tolerated and yielded clinically acceptable outcome among stage IA HER2-positive breast cancer. Methods: Patients with stage IA (T1N0: hormonal receptor (HR) < 10%, T≤2cm or HR≥10%, 1cm < T≤2cm) confirmed HER2+ BC were received oral capecitabine (1000 mg/m 2 twice daily for two weeks), and trastuzumab( 8 mg/kg load→6 mg/kg) every 3 weeks for 6 cycles, followed by 11 cycles of trastuzumab monotherapy (6 mg/kg once every 3 weeks). The primary end point was survival free from invasive disease (iDFS). Results: A total of 187 patients were enrolled in this study between May 20, 2020 and May 27, 2021 at Fudan University Shanghai Cancer Center in China. Among all these patients, 80.2% had tumors that measured 0.5 cm or less in the greatest dimension; a majority of tumors (87.2%) were hormone-receptor-negative. The median follow-up period was 62 months( ranges 56-68). The 5-year rate of survival free from invasive disease was 97.9% (95% confidence interval [CI], 94.4 to 99.2). Among the 4 relapses seen, 2 were due to contralateral primary invasive breast cancer (HER2-negative). Excluding these 2 patients and nonbreast cancers, 2 disease-specific events (1 with ipsilateral axilla and ipsilateral breast) were noted. There was no death in this trial. A total of 5 patients (2.7%) reported at least one episode of grade 3 adverse effect (AE)s, which did not influence the completion of treatment. The most common AE was hand-foot syndrome (46.5%), with 1.1% of patients experiencing a grade 3 event. Conclusions: Among patients with stage IA HER2+ BCs, treatment with adjuvant capecitabine plus trastuzumab was associated with an excellent 5-year iDFS of 97.9%. No adverse events that influence treatment continuity were observed. The regimen used in this trial would be an alternative in patients with small size HER2+ tumors with fewer toxic effects than the established regimens. A phase III study using the same protocol is being conducted currently. Clinical trial information: NCT04383275 .