Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer

Development ofHER2-targeted Therapies for Gastrointestinal Cancer

“…ClinicalTrials.gov identifier: NCT03329690), for patients with previously treated HER2-positive (IHC 3+ or 2+ and FISH-positive) metastatic gastric or GEJ cancer, was performed. 28,29 The results were reported recently; OS was longer with T-DXd than with the physician's choice of chemotherapy (median, 12.5 versus 8.4 months; p=0.01) and ORR in T-DXd was higher than that of chemotherapy (51 versus 14%, p<0.001). 28 Accordingly, the approval of this drug for clinical use is anticipated in Japan, where the SAKIGAKE designation system to promote driving early practical application for innovative pharmaceutical products has been granted for this indication.…”

“…These durations were significantly longer than those in the placebo group (i.e., 11.1 and 5.5 months, respectively) ( Table 1). 16,[18][19][20][21][22][23][24][25][26][27][28][29] In particular, in patients who were IHC 3+ or 2+ and fluorescence in situ hybridisation (FISH)-positive, trastuzumab with chemotherapy demonstrated remarkable efficacy, with a median OS of 16.0 months (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.51-0.83), whereas the survival benefit was not observed (HR 1.07, 95% CI 0.70-1.62) in patients with low levels of HER2 protein (IHC 0/1+ and FISH-positive). According to the survival benefit in patients with high HER2 expression, IHC 3+ or IHC 2+ and ISH-positive disease is considered positive for gastric cancer.…”

“…The median PFS was longer in the pertuzumab group than in the control group (8.5 versus 7.0 months; p=0.0001), and objective response rate Table 1). 28 Based on these promising results, the phase II DESTINY-Gastric01 trial (DS-8201a in human epidermal growth factor receptor 2 (HER2)-expressing gastric cancer;…”

CDK12 and HER2 coamplification in two urothelial carcinomas with rapid and aggressive clinical progression

“…In the two patient cases, CDK12 amplification accompanied with ERBB2 amplification was detected by targeted next‐generation sequencing in urothelial carcinomas. For patients with HER2 ‐positive advanced breast, gastric, or lung cancer, an anti‐HER2 Ab (trastuzumab deruxtecan) is reportedly effective 10‐12 . However, the effectiveness of anti‐HER2 therapy for breast cancers with CDK12 and ERBB2 coamplification is still unconfirmed 13,14 .…”

A case report on the long-term survival of a patient with HER2-positive metastatic gastric adenocarcinoma and a short review of the current literature

“…Concerning future directions, novel anti-HER2 approaches and combinations are gaining attention. A recent phase II trial showed promising results with the antibody-drug conjugate trastuzumab deruxtecan as a third and further line strategy for patients with HER2-positive advanced gastric cancer [30]. This option is expected to be practice-changing within the next couple of years.…”