In an updated analysis of DESTINY-Breast03, a head-to-head study vs T-DM1, ENHERTU demonstrated 28.8 months mPFS in 2L in patients with HER2+ mBC (6.8 months with T-DM1)1
- Initial analysis of mPFS (primary endpoint; May 2021 data cutoff): NR mPFS with ENHERTU (95% CI: 18.5, NE) vs 6.8 months with T-DM1 (95% CI: 5.6, 8.2); HR: 0.28 (95% CI: 0.22, 0.37; P<0.0001)2,3,a
Progression-free survivalb
Updated analysis (July 2022)1
- Updated exploratory PFS analysis was not tested for statistical significance and not powered to show differences between treatment arms
aMedian duration of follow-up for PFS (BICR) at initial data cutoff: 16.2 months (range: 0-32.7) for ENHERTU and 15.3 months (range: 0-31.3) for T-DM1.3
bMedian duration of follow-up for PFS (BICR) at updated analysis: 28.4 months (IQR: 22.1-32.9) for ENHERTU and 26.5 months (IQR: 14.5-31.3) for T-DM1.1
Similar mPFS results were observed in prespecified exploratory patient subgroups in the ENHERTU arm3
- Prespecified exploratory patient subgroups analyses were not powered to detect treatment effect differences between subgroups
In an updated analysis of DESTINY-Breast03, a head-to-head study vs T-DM1,
Superior overall survival with ENHERTU vs T-DM11
- Initial analysis of OS (key secondary endpoint; May 2021 data cutoff): OS was immature (16% of patients had died)2,3
Overall survivalc
Updated analysis (July 2022)1
- The 24-month landmark analysis is based on Kaplan-Meier estimates and is descriptive only; the DESTINY-Breast03 trial was not powered to assess a statistical difference between treatment groups at this time point
- NR mOS with ENHERTU (95% CI: 40.5 months, NE); NR mOS with T-DM1 (95% CI: 34.0 months, NE)
36% reduction in risk of death with ENHERTU over T-DM1 in 2L (key secondary endpoint; HR: 0.64; 95% CI: 0.47, 0.87; P=0.0037)
cEfficacy boundary for superiority: P=0.013 (based on 169 events).1
In an updated analysis of DESTINY-Breast03, a head-to-head study vs T-DM1,
ENHERTU delivered 82.1% confirmed ORR, more than double the 36.7% T-DM1 response4
- Initial analysis of confirmed ORR as
assessed by
BICR
(secondary endpoint; May 2021 data cutoff)2,3,d:
- 82.7% with ENHERTU (n=205/248; 95% CI: 77.4, 87.2; 15.7% CR [n=39] + 66.9% PR [n=166])
- 36.1% with T-DM1 (n=87/241; 95% CI: 30.0, 42.5; 8.3% CR [n=20] + 27.8% PR [n=67])
Confirmed objective response ratee
Updated analysis (July 2022)1,4
- ORR was not tested for statistical significance and not powered to show differences between treatment arms
~98% of patients had disease control with ENHERTU (21.1% CR [n=52] + 61.0% PR [n=150] + 15.4% SD [n=38])1
dAnalysis was performed based on the patients with measurable disease assessed by BICR at baseline (n=248 patients randomized to receive ENHERTU: n=241 for TDM1).2
eAnalysis was performed based on the patients with measurable disease assessed by BICR at baseline (n=246 patients randomized to receive ENHERTU: n=240 for TDM1).4
In DESTINY-Breast03, a head-to-head study vs T-DM1,
The majority of patients had a tumor response with ENHERTU3
Best percent change from baseline in the sum of diameters of measurable tumors (exploratory endpoint)
fOnly subjects with measurable disease at baseline and at least one postbaseline target lesion assessment are included.
THE ONLY CATEGORY 1,
Preferred Option in 2L
HER2+ mBC5
NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) recommends fam-trastuzumab deruxtecan-nxki
(ENHERTU)
as Category 1, preferred option as second-line therapy for recurrent
unresectable (local or regional) stage IV HER2+ disease5,g
NCCN Clinical Practice
Guidelines in Oncology
(NCCN
Guidelines®) Preferred
THE ONLY CATEGORY 1,
Preferred Option in 2L
HER2+ mBC5
NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines®) recommends fam-trastuzumab deruxtecan-nxki
(ENHERTU)
as Category 1, preferred option as second-line therapy for recurrent
unresectable (local or regional) stage IV HER2+ disease5,g
gFam-trastuzumab deruxtecan-nxki may be considered in the first-line metastatic setting as an option for select patients (ie, those with rapid progression within 6 months of neoadjuvant or adjuvant therapy [12 months for pertuzumab-containing regimens]).5
2L, second line; BICR, blinded independent central review; CI, confidence interval; CR, complete response; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; HR-, hormone receptor negative; HR+, hormone receptor positive; IQR, interquartile range; mBC, metastatic breast cancer; mOS, median overall survival; mPFS, median progression-free survival; NCCN, National Comprehensive Cancer Network® (NCCN®); NE, not evaluable; NR, not reached; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; SD, stable disease; T-DM1, ado-trastuzumab emtansine.