Adjuvant Capecitabine and Trastuzumab for Stage IA HER2-Positive Breast Cancer (IRIS-A): A Phase II Clinical Trial

Abstract BACKGROUND : The IRIS-A trial was a single-group, phase II study to determine whether treatment with capecitabine and trastuzumab was well tolerated and yielded clinically acceptable outcomes among patients with stage IA (T1N0) human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC). Patients and Methods : Patients with confirmed stage IA (T1N0: hormone receptor (HR)-, T≤2 cm or HR+, 1 cm<T≤2 cm) HER2+ BC received oral capecitabine (1000 mg/m 2 twice daily for two weeks) and trastuzumab every 3 weeks for 6 cycles, followed by 11 cycles of trastuzumab monotherapy. The primary end point was survival free from invasive disease (iDFS). Results: A total of 187 patients were enrolled in the 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 the tumors (87.2%) were HR negative. The median follow-up period was 66 months (range 60–72 months). The 5-year survival rate of patients who were free from invasive disease was 97.8% (95% confidence interval [CI], 94.3 to 99.1). Among the 4 patients who relapsed, 2 relapsed because of contralateral primary invasive breast cancer (HER2-negative). After these 2 patients and nonbreast cancer patients were excluded, 2 disease-specific events (1 involving the ipsilateral axilla and the ipsilateral breast) were noted. There were no deaths in this trial. Grade 3 adverse effects were reported in 5 patients (2.7%) but did not influence the completion of treatment. The most common adverse event was hand‒foot syndrome (46.5%), with 1.1% of patients experiencing a grade 3 event. Conclusion : Adjuvant capecitabine plus trastuzumab was associated with an excellent 5-year iDFS in 97.8% of patients with stage IA HER2+ BC. No adverse events that influence treatment continuity were observed (ClinicalTrials.gov number, NCT04383275).