Cortés J, Diéras V, Lorenzen S, et al. - Although ERBB2 (HER2)-targeted therapy effectively manages metastatic breast cancer (mBC) and gastric cancer, maximizing effectiveness and quality of life requires supplementary treatments. Researchers conducted this phase 1/2 randomized clinical trial to determine how the addition of capecitabine to trastuzumab emtansine (T-DM1) treatment impacted outcomes among 161 patients with previously treated ERBB2-positive metastatic breast cancer. Further, in patients with previously treated ERBB2-positive mBC and locally advanced/metastatic gastric cancer (LA/mGC) they assessed the maximum tolerated doses (MTDs) of T-DM1 plus capecitabine and then compared the safety and efficacy of this combination with T-DM1 monotherapy. In the phase 1 mBC cohort, participants were administered capecitabine (750 mg/m2, 700 mg/m2, or 650 mg/m2 twice daily, days 1-14 of a 3-week cycle) with T-DM1 3.6 mg/kg every 3 weeks. Capecitabine was administered to participants with LA/mGC at the mBC phase 1 MTD, de-escalating as required, in combination with T-DM1 2.4 mg/kg weekly. For phase 2, either capecitabine (at the phase 1 MTD) in combination with T-DM1 or T-DM1 alone was randomly administered to patients with mBC at a 1:1 ratio. In 11 patients with mBC and 6 with LA/mGC who could be evaluated for dose-limiting toxic effects, the MTD for capecitabine when combined with TDM1 was determined to be 700 mg/m2 (phase 1). For phase 2, capecitabine in addition to T-DM1 led to more the toxic effects while not significantly improving clinical outcomes vs T-DM1 alone in previously treated ERBB2-positive metastatic breast cancer patients.