Abstract
This network meta-analysis addresses the need for evidence-based best-practice treatment regimens for HER2-positive breast cancer. We compared the relative efficacy and tolerability of currently available HER2-positive neoadjuvant immunotherapy regimens based on systematic searches of available randomized controlled trials (RCTs) data. Based on intention-to-treat principle, pathological complete response (pCR), overall serious adverse events (SAEs), and breast-conserving surgery (BCS) rate were analyzed using random-effect, Bayesian network meta-analysis, and standard pairwise meta-analysis. 16 RCTs (3868 patients) were included. Analyzed treatment regimens were as follows: chemotherapy+trastuzumab+pertuzumab (CTP), trastuzumab emtansine+pertuzumab (MP), chemotherapy+trastuzumab (CT), chemotherapy+pertuzumab (CP), trastuzumab+pertuzumab (TP), chemotherapy+trastuzumab+lapatinib (CTL), and chemotherapy+lapatinib (CL), and chemotherapy (C) alone. We found that, for the chance of achieving pCR, CTP was ranked first (SUCRA: 97%), followed by CTL, MP, and CT (SUCRA: 80%, 75%, and 55%, resp.). MP provided the safest regimen (SUCRA: 97%), then TP, C, and TPC (SUCRA: 82%, 76%, and 47%, resp.). CTL proved the most toxic therapy (SUCRA: 7%). No significant difference between neoadjuvant regimens was identified for BCS. Hormone receptor status did not impact ORs for pCR in any regimen. In conclusion, our findings support CTP as the optimum neoadjuvant regimen for HER2-positive breast cancer, with the best pCR and acceptable toxicity compared with CT. MP provides a therapeutic option for patients with poor performance status.
Highlights
Worldwide, breast cancer is one of the most common malignancies and the leading cause of death in females, with an estimated 1.7 million new diagnoses annually [1]
We investigated the presence of small-study effects for each outcome by comparison-adjusted funnel plots; comparisons have been directed according to the effectiveness of neoadjuvant regimens, assuming that the more effective regimens are favored in small trials [38, 39]
After further fulltext evaluation for the remaining 139 records, 22 publications [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61] pertaining to 16 distinct neoadjuvant trials were considered eligible for this meta-analysis, which comprised a total of 3868 patients
Summary
Breast cancer is one of the most common malignancies and the leading cause of death in females, with an estimated 1.7 million new diagnoses annually [1]. The individual patient’s response to neoadjuvant regimen, designated as pathological complete response (pCR) in the breast and axillary nodes at the time of surgery, is strongly correlated with improved overall survival (OS) and disease-free survival (DFS), in triple-negative and HER2-positive diseases [7]. For this reason, the neoadjuvant approach using pCR as a surrogate endpoint has been adopted to accelerate the approval of new agents for high-risk early-stage breast cancers by the U.S Food and Drug Administration (FDA) [8, 9] and European Medicines Agency (EMA) [10, 11]. Data from random controlled trials (RCT) has shown that regimens in neoadjuvant settings have similar OS and DFS compared with that in adjuvant trials, and more breast-conserving surgery (BCS) can be performed after neoadjuvant regimens because of tumor shrinkage, providing additional support for this approach [12, 13]
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