Kadcyla Plus Capecitabine in HER2-Positive Metastatic Breast Cancer: Phase 1/2 Trial

On June 25, 2020, Javier Cortés and colleagues published the results of a Phase 1 and Randomized Phase 2 clinical trial in JAMA Oncology. The study investigated whether combining Kadcyla (Trastuzumab emtansine, T-DM1) with Capecitabine (Xeloda) would enhance efficacy in patients with previously treated HER2-positive metastatic breast cancer.

Study Design

The trial randomized 161 patients into two groups:

1. Kadcyla Monotherapy Group (N=80): 3.6 mg/kg every three weeks.
2. Combination Group (N=81): Kadcyla (3.6 mg/kg) + Capecitabine (administered at varying doses, e.g., 700 mg/m² twice daily on days 1–14 of a 21-day cycle).

The primary endpoint for the Phase 2 portion was the objective response rate (ORR).

Key Efficacy Results

The trial results showed a modest but not statistically significant difference in response:

• Objective Response Rate (ORR): 44% for the combination group vs. 36% for the monotherapy group.
• Progression-Free Survival (PFS): There was no significant improvement in the time patients lived without their disease worsening between the two groups.

Safety Profile

The incidence of Grade 3 or 4 adverse events was slightly higher in the combination group (44%) compared to the monotherapy group (41%). Common side effects included gastrointestinal symptoms and hand-foot syndrome typical of capecitabine. No Grade 5 (fatal) toxicities were reported.

Conclusion

Dr. Javier Cortés and the research team concluded that adding Capecitabine to Kadcyla did not result in a statistically significant improvement in objective response rates for patients with pretreated HER2-positive metastatic breast cancer. Based on these findings, T-DM1 monotherapy remains the standard of care in this setting.

Source: JAMA Oncology - T-DM1 Plus Capecitabine Trial Results

#BreastCancer #HER2Positive #Kadcyla #TDM1 #Capecitabine #Xeloda #CancerResearch

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