HER2+ mBCa: capecitabine added to T-DM1 fails to improve outcomes in TRAXHER2 trial

  • JAMA Oncol

  • curated by Miriam Davis, PhD
  • Univadis Clinical Summaries
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Takeaway

  • Trastuzumab emtansine (T-DM1)+capecitabine (vs T-DM1 alone) had high toxicity and no added benefit in patients with previously treated HER2+ metastatic breast cancer (mBCa) in the phase 2 TRAXHER trial.
  • The phase 1 component defined the maximum tolerated dose (MTD) of capecitabine at 700 mg/m2 for HER2+ mBCa and HER2+ locally advanced/metastatic gastric cancer (LA/mGC).

Why this matters

  • Combined T-DM1 and capecitabine does not warrant further testing for patients with previously treated HER2+ mBCa.

Study design

  • International phase 2 trial of 81 patients randomly allocated to combination therapy (with capecitabine at the MTD) vs 80 patients assigned to T-DM1 alone (3.6 mg/kg).
  • Funding: F. Hoffmann-La Roche, Ltd.

Key results

  • The capecitabine MTD was 700 mg/m2 (n=11 with mBCa and n=6 with LA/mGC) in the phase 1 component.
  • In the phase 2 component, no difference was found in objective response rate (44.4% of the combination group vs 36.3% of the T-DM1 group; P=.34) in patients with previously treated HER2+ mBCa.
  • Median OS was not estimable (NE) for the combination group (NE; 90% CI, NE-NE) and 24.7 months for the T-DM1 group (stratified HR, 0.87; 90% CI, 0.51-1.48).
  • Adverse events of all grades were observed in 95% of the combination group (44% with grades 3-4) and 88% of the T-DM1 group (41% with grades 3-4).

Limitations

  • Open-label.