Trastuzumab emtansine (T-DM1) is a suitable first-line therapy for patients with HER2-positive, advanced breast cancer who cannot receive taxane-based therapy, according to researchers.
Final results from the phase 3 MARIANNE trial revealed similar overall survival (OS) in patients who received T-DM1, T-DM1 plus pertuzumab, or trastuzumab plus a taxane (HT). All three regimens resulted in a median OS exceeding 50 months.
The incidence of grade 3 or higher adverse events (AEs) was highest in patients who received HT.
, of Mayo Clinic Cancer Center in Jacksonville, Fla., and colleagues reported these results in .
The MARIANNE trial () enrolled 1,095 adults with HER2-positive, advanced breast cancer. They were randomized to receive HT, T-DM1, or T-DM1 plus pertuzumab. Patients in the HT arm received trastuzumab plus paclitaxel or docetaxel according to the investigator’s discretion.
In all, 352 patients received HT (257 on docetaxel and 96 on paclitaxel), 361 patients received T-DM1 plus placebo, and 366 received T-DM1 plus pertuzumab.
Response and OS
In the primary analysis, the median OS was not reached in any treatment arm at a median follow-up of 35 months. The rate of objective response was 67.9% in the HT arm, 64.2% in the T-DM1 plus pertuzumab arm, and 59.7% in the T-DM1 arm. The median duration of response was 12.5 months, 21.2 months, and 20.7 months, respectively.
For the final OS analysis, the median duration of follow-up was 54 months. Roughly 70% of patients in each arm had received at least one treatment regimen during follow-up.
The final median OS was similar across the treatment arms – 50.9 months in the HT arm, 53.7 months in the T-DM1 arm, and 51.8 months in the T-DM1 plus pertuzumab arm. With the HT arm as a reference, the stratified hazard ratio was 0.93 for the T-DM1 arm and 0.86 for the T-DM1 plus pertuzumab arm.
OS results were consistent across subgroups. Although there were some differences in hazard ratios, “none of the examined subgroups showed a clear benefit with one treatment regimen in comparison with the others,” the researchers wrote.
The researchers also analyzed OS by response status at 6.5 months after randomization. Among nonresponders, the median OS was 41.9 months in the T-DM1 plus pertuzumab arm, 45.7 months in the T-DM1 arm, and 48.1 months in the HT arm. Among responders, the median OS was not reached in the T-DM1 plus pertuzumab arm, 64.4 months, and 56.3 months, respectively.
There were no baseline characteristics or biomarkers that were strongly associated with response by treatment group. However, in the HT and T-DM1 arms, patients with above-median HER2 messenger RNA expression were more likely to respond.
Rates of grade 3 or higher AEs were 55.8% in the HT arm, 47.1% in the T-DM1 arm, and 48.6% in the T-DM1 plus pertuzumab arm. The most common grade 3 or higher AEs were as follows:
- HT arm – neutropenia (19.3%), febrile neutropenia (6.5%), and diarrhea (4.2%).
- T-DM1 arm – increased aspartate aminotransferase (6.9%), thrombocytopenia (6.6%), and anemia (5.0%).
- T-DM1 plus pertuzumab arm – thrombocytopenia (9.0%), anemia (7.1%), and increased alanine aminotransferase (6.0%).
Rates of AE-related treatment discontinuation were 20.8% in the T-DM1 arm, 23.0% in the T-DM1 plus pertuzumab arm, and 30.6% in the HT arm. Rates of AE-related death were 1.4%, 1.9%, and 2.0%, respectively.
This study was funded by F. Hoffmann–La Roche. Dr. Perez was previously employed by Genentech/Roche. Her fellow authors disclosed relationships with Roche and many other companies.
SOURCE: Perez EA et al. Cancer. 2019 Jul 18. .