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ASCO Webinar Summary: Gastric Cancer

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)

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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.
Regimen n


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%
vs. vs. vs. vs. vs. vs. vs. vs.
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.

(HR: 1.13)

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.

 Key take-away:

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.

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