Purpose: Numerous HER2-targeted therapy clinical trials have demonstrated efficacy and safety in the first-line treatment of metastatic breast cancer (MBC). However, the direct or indirect comparison of these drugs is unclear. This network meta-analysis can solve this issue to some extent.
Materials and methods: PubMed, Embase, and the Cochrane Library were searched for Phase II/III randomized controlled trials (RCTs) on metastatic HER2-positive breast cancer for first-line treatment up to December 16, 2017. Paired meta-analyses were performed to compare the regimens directly with the TP (trastuzumab plus taxane) regimen. Bayesian network meta-analysis was used to synthesize available evidence of direct or indirect comparison.
Results: The database search identified 1,935 articles, among which 13 articles (10 RCTs) were eligible for the analysis involving 5,177 patients treated with 11 different regimens. The progression-free survival (PFS) in the Bayesian network meta-analysis suggested that the PTP (pertuzumab and trastuzumab plus taxane) regimen had the highest probability to be the preferred treatment (surface under the cumulative ranking [SUCRA]: 0.967) followed by the TPC (carboplatin and trastuzumab plus taxane) regimen (SUCRA: 0.923). The PTP regimen (SUCRA: 0.926) was similarly preferred for overall survival (OS). For objective response rate (ORR), the PTC regimen might be the optimal treatment (SUCRA: 0.935), followed by the PTP regimen.
Conclusion: Overall, PTP might be the optimal first-line treatment for HER-2-positive MBC to improve the PFS and OS. Meanwhile, TPC might be most effective treatment in terms of the ORR. Regarding safety, the two regimens showed acceptable grade 3 or greater hematologic toxicity and heart failure.
Keywords: breast cancer, metastasis, HER2-positive, HER2-targeted agents, network meta-analysis, randomized controlled trial