DESTINY-Gastric01: OS benefit of T-DXd over chemotherapy for HER2-positive gastric cancer

The final results of the phase 2 DESTINY-Gastric01 trial showed that trastuzumab deruxtecan (T-DXd) was superior to a standard PC chemotherapy regimen in patients with HER2-positive advanced gastric or gastroesophageal cancer. Also, the updated safety data were consistent with the primary analysis of this study [1].

The open-label, multicentre, phase 2 DESTINY-Gastric01 trial (NCT03329690) included 188 patients with HER2-positive advanced gastric or gastroesophageal cancer who had undergone 2 or more prior lines of therapy, including fluoropyrimidine and a platinum agent. Participants were randomised 2:1 to T-DXd, 6.4 mg/kg every 3 weeks, or a standard PC chemotherapy regimen (i.e. irinotecan and/or paclitaxel). In the primary analysis, T-DXd outperformed PC chemotherapy on the primary endpoint of objective response rate (ORR) by independent central review. Dr Kensei Yamaguchi (Cancer Institute Hospital of JFCR, Japan) presented the final results of this trial.

The ORR was 51.3% in the T-DXd arm compared with 14.3% in the PC arm (P<0.0001). In the T-DXd arm, 9.2% of the patients displayed a complete response and 42.0% of the patients had a partial response. In addition, 35.5% of the patients in the T-DXd arm demonstrated stable disease. The median duration of response was 12.5 months in patients receiving T-DXd versus 3.9 months in patients receiving chemotherapy. The updated overall survival (OS) analysis, with a maturity of 71.1%, represented superior anti-tumour activity of T-DXd over chemotherapy (median OS 12.5 vs 8.9 months; see Figure). Dr Yamaguchi added that the 40% reduced risk of death in patients receiving T-DXd is a clinically meaningful OS benefit.

Figure: Overall survival in DESTINY-Gastric01 [1]



The updated safety analysis did not show unexpected safety issues. Grade 3 or higher adverse events (AEs) were more common among T-DXd receivers than among chemotherapy receivers (85.6% vs 56.5%). The most frequently reported grade 3 or higher AEs in the T-DXd arm were decreased neutrophil count (51.2%), anaemia (38.4%), and decreased white blood cell count (20.8%). Notably, 12.8% of the patients receiving T-DXd displayed interstitial lung disease (ILD)/pneumonitis after a median time to first onset of 102.5 days; 13 out of 16 cases of ILD/pneumonitis were grade 1 or 2 events, none were grade 5.

Dr Yamaguchi concluded that these updated results confirm that T-DXd has potential as a treatment option for patients with HER2-positive advanced gastric or gastroesophageal junction cancer after 2 or more previous lines of therapy.

1. Yamaguchi K, et al. Trastuzumab Deruxtecan (T-DXd; DS-8201) in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma: Final Overall Survival (OS) Results From a Randomized, Multicenter, Open-Label, Phase 2 Study (DESTINY-Gastric01). Rapid Abstracts Session A, ASCO GI 2022, 20–22 January.

 

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Posted on 21 March, 202227 March, 2024