TDM-1 efficacy in trastuzumabpertuzumab pre-treated HER2 positive metastatic breast cancer patients: a meta-analysis

Background: Based on the results reported in Emilia trial population, current guidelines consider TDM-1 the standard 2nd line therapy for HER2 positive metastatic breast cancer (MBC) patients. Despite that, there are no prospective studies supporting the efficacy of TDM-1 following trastuzumab (T) + pertuzumab (P) and taxane 1st line treatment. Currently, only real-world data have investigated this sequence with controversial results. Methods: We performed a meta-analysis of the available real world data to determine the efficacy of T-DM1 after 1st line TP in HER2 positive MBC patients. We used a random- effect model to find differences in the rate of 1-year progression free survival (PFS) between TP pre-treated population and the phase III Emilia trial (T pre-treated population). Results: Seven studies were eligible, in three of them data were from sub-group population analysis. The meta-analysis showed a combined 1-years PFS risk difference for TDM-1 efficacy after TP in 2nd or more lines of -0.122, with lower and upper limits of -0.253 and 0.010, respectively (p=0.07), with low heterogeneity among studies (I2 < 0.0001, p =0.836). Considering the four studies on TDM-1 in 2nd line setting, 1-years PFS risk was -0.034 (95% CI -0.207 – 0,139; p=0.701) (I2 < 0.0001, p =0.91). Conclusions: Results from the meta-analysis show that the efficacy of TDM-1 after TP double-block seems to be similar to the previously reported in Emilia trial. In the second line setting, available data are not mature enough to confirm TDM-1 efficacy in TP pre-treated population. Currently, TP pretreated patients should receive T-DM1 as indicated in the guidelines.