Optimum adjuvant trastuzumab duration for human epidermal growth factor receptor-2 positive breast cancer: a network meta-analysis of randomized trials

BACKGROUND: Adjuvant trastuzumab treatment for 12 months is the standard-of-care for early HER2-positive breast cancer; however, the optimal duration is unclear. We performed a network meta-analysis (NMA) to determine the optimal treatment duration. METHODS: We identified 16 randomized controlled trials involving 29,837 patients that assessed trastuzumab treatment in HER2-positive early breast cancer. Our NMA compared six trastuzumab durations: observation, T-9 weeks, T-12 weeks, T-6 months, T-12 months, and T-24 months. We assessed overall survival (OS), disease-free survival (DFS), acceptability, and cardiotoxicities and grade 3–4 nonhematologic toxicities, and ranked the durations in terms of efficacy and safety by surface under the cumulative ranking (SUCRA). RESULTS: Pairwise meta-analysis showed that while T-6 months was associated with a significant reduction in DFS compared to T-12 months. In our NMA, increasing or decreasing durations showed a significant benefit in DFS compared to observation; however, decreasing durations was not associated with a significant reduction in DFS compared with T-12 months, regardless of the lymph node and hormone receptor statuses. SUCRA ordered the optimum durations of trastuzumab treatment based on PFS as T-12 months (95.6%), T-24 months (69.6%), T-6 months (53.2%), T-9 weeks (41.2%), T-12 weeks (34.3%) and observation (6.1%). CONCLUSIONS: Escalating trastuzumab treatment beyond T-12 months confers no additional survival benefit but increased risk of cardiotoxicities. Furthermore, de-escalating treatment confers no improvement on OS compared to T-12 months. These data suggest that T-12 months is the most appropriate treatment schedule for HER2-positive early breast cancer.