Trastuzumab deruxtecan (T-DXd; DS-8201) in patients with HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: A randomized, phase II, multicenter, open-label study (DESTINY-Gastric01)
Author, Company: Kohei Shitara, MD
Abstract Number: 4513
Indications: Advanced HER2+ gastric or gastroesophageal junctional adenocarcinoma
Interventions: Enhertu (Trastuzumab deruxtecan)
Background and objectives:
- In DESTINY-Gastric01 i.e. a randomised open-label, multicentre, randomized, phase II study of T-DXd (antibody-drug conjugate) in HER2+ advanced GC or GEJ adenocarcinoma, a comparison was made between the use of trastuzumab deruxtecan with physician’s choice(PC) of standard chemotherapy in patients
- The primary measure outcome was ORR and secondary endpoints were OS, PFS, DOR, DCR and safety. Patients had a median of 2 prior lines of therapy.
|ORR||Confirmed ORR||Confirmed DCR||Confirmed mDOR||mOS||mPFS||Grade ≥ 3 AEs|
|T-DXd vs PC (irinotecan or paclitaxel)||125||51.3%||42.9%||85.7%||11.3 mo.||12.5 mo.||5.6 mo.||85.6%|
|62||14.3%||12.5%||62.5%||3.9 mo.||8.4mo. (HR:0.59)||3.5 mo. (HR:0.47)||56.5%|
Results and observations:
- Both Kadcyla and Enhertu use trastuzumab but they use different linkers and payloads. The phase II/III GATSBY trial resulted in no survival difference between ado-trastuzumab emtansine vs taxane treatment in patients with previously treated locally advanced GC or GEJ adenocarcinoma
|Kadcyla vs Chemo||Enhertu vs Chemo|
|Median OS||7.9 mo. vs 8.6 mo.
|12.5 mo. vs 8.4 mo.
|Median PFS||2.7 mo. vs 2.9 mo.
|5.6 mo. vs. 3.5 mo.
T-DXd revealed statistically significant and clinically meaningful improvements in ORR and OS versus standard chemotherapy (paclitaxel or irinotecan) in patients with HER2+ advanced gastric or GEJ adenocarcinoma. It was well tolerated and had no significant safety concerns.
The Destiny-Gastric01 trial revealed that Enhertu is the first HER2-directed therapy to show an OS benefit and gave a gold standard in evaluating cancer treatments for previously treated HER2+ve gastric cancer, with a potential to become the SoC in this setting.