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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)

( https://meetinglibrary.asco.org/record/185492/abstract )

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

Size

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.

(HR:1.1)

12.5 mo. vs 8.4 mo.

(HR:0.59)

Median PFS 2.7 mo. vs 2.9 mo.

(HR: 1.13)

5.6 mo. vs. 3.5 mo.

(HR:0.47)

 Conclusion:

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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