Post-ASCO 2022: Summary of key breast cancer highlights
With the conclusion of another ASCO, we were presented with exciting new breakthrough data of Antibody Drug Conjugates in breast cancer. Enhertu (trastuzumab deruxtecan) demonstrated significant benefit in the treatment of a new subtype of breast cancer, HR+/ /HER2-low. Trodelvy (sacituzumab govitecan) on the other hand produced a modest yet statistically significant improvement over standard of care in heavily pre-treated HR+/HER2- BC.
DESTINYBreast-04: HER2-low the new high point of mBC treatment?
DESTINYBreast-04 (DB-04) study is the 1st Phase 3 trial of Enhertu in patients with HER2-low mBC, defined as IHC 1+ and IHC 2+/ISH- HER2 expression (~50% of BC), that showed a statistically significant and clinically meaningful benefit in PFS and OS compared to SOC in pts regardless of ER status.
The study enrolled 557 pts with centrally confirmed HER2-low mBC and were randomly assigned 2:1 to Enhertu 5.4 mg/kg or physician’s choice of chemotherapy (TPC):
- In HR+/HER2-low mBC pts, Enhertu showed a 49% reduction in the risk of disease progression or death vs TPC with a mPFS of 10.1 mos in pts treated with Enhertu vs. 5.4 mos in TPC, as assessed by BICR
- The study also met its key secondary endpoint by showing a 36% reduction in the risk of death with Enhertu vs TPC in patients with HR+ (OS HR 0.64) with a mOS of 23.9 mos with Enhertu compared to 17.5 mos with TPC
- Benefit was also observed in HR-/HER2-low patients, where Enhertu had a PFS of 8.5 mos vs 2.9 mos in TPC (HR: 0.46) with an OS of 18.2 mos vs 8.3 mos in TPC (HR: 0.48)
The data was well received by the scientific community at ASCO 2022 and is expected to drive the investigation of the ADC in other tumor types.
While considered to be practice changing, HCPs may begin using Enhertu as an alternative to chemotherapy after progression on ET, with agents targeting the ER-axis taking precedence. The need for better testing and concordance on the definition of HER2+ was emphasised, suggesting that further innovation is needed to help identify patients that can benefit from Enhertu. Additionally, the mechanism of resistance to Enhertu is still largely unknown and needs to be researched further.
TROPiCS-02: Modest but incremental benefit in a new breast cancer subtype, regardless of TROP-2 expression
TROPiCS-02 is a Phase 3 study evaluating Trodelvy (approved for 2L mTNBC), a TROP-2 targeted ADC, in patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and 2-4 lines of chemotherapy. TROP-2 is known to be overexpressed in breast cancer subtypes, which provided the basis for its investigation and eventual approval in TNBC in 2020. To build on its first approval, TROPiCS-02 explored Trodelvy in another breast cancer subtype, HR+/HER2-low, which met the primary endpoint in March 2022. The results were presented for the first time at ASCO 2022 by Dr. Rugo as a late-breaking abstract.
TROPiCS-02 met its primary endpoint with a statistically significant improvement in progression-free survival (PFS) versus physician’s choice of chemotherapy, 1.5 months improvement over control (5.5 vs 4.0 mos; HR: 0.66). PFS rates at 6 and 12-months were 46% vs 30% and 21% vs 7%.
While the improvement in median PFS is relatively modest, the early drop in KM curves of the heavily treated patient population seem to have impacted the results. However, PFS rates at 6-months and 12-months were deemed to be encouraging. Therefore, if Trodelvy is able to demonstrate significant OS benefit from the additional interim analyses that are planned, it can emerge as the preferred treatment of choice vs chemotherapy for heavily pre-treated patients who will have failed several lines of therapy.
Only data, time, and dynamics around preferences for testing will further tell us how these ADCs will be utilised in treatment practice.
Deallus’ passion in oncology and innovation will continue to drive us to closely follow the latest breakthroughs beyond ASCO. As part of our expertise spectrum, we look forward to bringing further insights on the clinical progress within the oncology space.
