by Hope S. Rugo, Eduardo J. Pennella, Unmesh Gopalakrishnan,
Miguel Hernandez-Bronchud, Jay Herson, Hans Friedrich Koch, Subramanian
Loganathan, Sarika Deodhar, Ashwani Marwah, Alexey Manikhas, Igor Bondarenko,
Joseph D. Parra, Maria Luisa T. Abesamis-Tiambeng, Charuwan Akewanlop, Ihor
Vynnychenko, Virote Sriuranpong, Sirshendu Roy, Eduardo Patricio Yanez Ruiz,
Abhijit Barve, Cornelius F. Waller
The Breast: Published:
March 31, 2021
Background
Trastuzumab-dkst is a biosimilar of trastuzumab. The phase 3
HERITAGE trial demonstrated equivalent overall response rate (ORR) with
trastuzumab-dkst or originator trastuzumab at 24 weeks in patients with
HER2-positive metastatic breast cancer receiving chemotherapy. We now present
the correlation of ORR with progression-free survival (PFS) for maintenance
monotherapy with trastuzumab-dkst vs trastuzumab at 48 weeks of treatment, and
the safety, tolerability, and immunogenicity.
Methods
HERITAGE is a multicenter, double-blind, randomized,
parallel-group, phase 3 study. Patients were randomized 1:1 to receive
trastuzumab-dkst or trastuzumab in combination with taxane followed by
continued monotherapy until disease progression. The analysis included PFS at 48
weeks to support the primary efficacy endpoint of ORR and safety, tolerability,
and immunogenicity of trastuzumab-dkst vs trastuzumab as maintenance
monotherapy.
Results
Of 500 randomized patients, 342 entered the monotherapy
phase; 214 patients received ≥48 weeks of treatment. There were no
statistically significant differences between PFS, ORR, or interim overall
survival at week 48 between trastuzumab-dkst and trastuzumab. Week 24 ORR was
highly correlated with week 48 PFS (rb = 0.75). Cumulative treatment-emergent
adverse events (TEAEs) and serious AEs were similar in both groups, with few
grade ≥3 TEAEs. Immunogenicity was low and similar in both groups at 48 weeks.
Conclusion
The correlation between ORR and PFS supports the design of
first-line metastatic trials assessing biosimilar trastuzumab. Overall,
trastuzumab-dkst and trastuzumab were well tolerated with similar efficacy,
including ORR and PFS, in combination with a taxane followed by monotherapy.
