Incidence of LVEF decline
A total of 7,184 patients receiving dual HER-2 blockade in 15 RCTs were available for LVEF decline analysis. There were 302 LVEF decline events among these patients. The highest incidence (8.7%; 95% CI 5.3% to 13.9%) was observed in a phase III breast cancer neoadjuvant trial of trastuzumab plus lapatinib when concomitant with paclitaxel [22], while the lowest incidence was observed in four trials in which no events of LVEF decline occurred[16, 27, 31, 37]. Using a random-effects model (χ2-based Q statistic test: Q= 31.75; p =0.004;I 2 = 55%), the summary incidence of LVEF decline in cancer patients treated with dual HER2 blockade was 4.6% (95% CI, 3.7% to 5.7%, figure 2A).
For LVEF decline associated with anti-HER2 monotherapy, the highest incidence (13.4%; 95% CI 10.2% to 17.4%) was observed in NSABP protocol B-41 trial[30], while no events of LVEF decline occurred in three trials[16, 19, 37]. Using a random-effects model (χ2-based Q statistic test: Q=108.33;p <0.001; I 2=86%), the summary incidence of LVEF decline in cancer patients treated with anti-HER2 monotherapy was 3.2% (95% CI, 2.2% to 4.6%, figure 2B).