Real-world effectiveness and safety of trastuzumab-deruxtecan in Japanese patients with HER2-positive advanced gastric cancer (EN-DEAVOR study)

Abstract

Background: Trastuzumab-deruxtecan (T-DXd) was approved for the treatment of HER2-positive patients with advanced gastric cancer in Japan based on the results of the DESTINY-Gastric01 trial. This study aimed to collect real-world data and evaluate the effectiveness and safety of T-DXd.

Methods: Patients aged ≥ 20 years at the start of T-DXd administration with a histopathologically confirmed diagnosis of HER2-positive unresectable advanced or recurrent gastric or gastroesophageal junction (GEJ) adenocarcinoma that had worsened after chemotherapy were enrolled in this retrospective cohort study. Key outcomes included T-DXd treatment status, overall survival (OS), real-world progression-free survival (rwPFS), time to treatment failure (TTF), objective response rate and frequency of grade ≥ 3 adverse events (AEs).

Results: Of the 312 patients included in the analysis, 75.3% were male, the median (range) age was 70.0 (27.0-89.0) years, 12.2% had an ECOG PS ≥ 2, 43.3% had ascites and the initial T-DXd dose was > 5.4- ≤ 6.4 mg/kg in 78.2% of patients. The median (95% confidence interval) OS, rwPFS and TTF (months) was 8.9 (8.0-11.0), 4.6 (4.0-5.1) and 3.9 (3.4-4.2), respectively. The response rate was 42.9% in patients with a target lesion. In total, 48.4% of patients experienced a grade ≥ 3 AE, 2.6% experienced grade 5 AEs and 60.9% experienced AEs leading to T-DXd dose adjustments (reduction: 36.9%, interruption: 34.0% or discontinuation: 23.7%). No new safety signals were detected.

Conclusions: T-DXd was effective and had a manageable safety profile as a third- or later-line treatment for patients with HER2-positive gastric or GEJ cancer in Japanese clinical practice.

Clinical trial registration: UMIN000049032.

Keywords: Effectiveness; Gastric cancer; HER2-positive; Japan; Post-marketing surveillance; Real world; Safety; Third- or later-line; Trastuzumab-deruxtecan (T-DXd).

Fig. 1

Treatment status of T-DXd. T-DXd, trastuzumab-deruxtecan

Fig. 2

Survival outcomes of T-DXd: A OS rate, B rwPFS rate and (C). TTF rate. The median (95%) CI time was determined using the Brookmeyer and Crowley method. CI confidence interval, OS overall survival, rwPFS real-world progression-free survival, TTF time to treatment failure, T-DXd trastuzumab-deruxtecan

Fig. 3

Best percentage change from baseline in sum of diameters of target lesions. IHC immunohistochemistry, ISH in situ hybridisation, Nivo, nivolumab; Pembro, pembrolizumab

Fig. 4

Subgroup analysis of OS. The underlined values are for Group B (reference). ^aBrookmeyer and Crowley method. ^bUsing the univariate Cox’s proportional hazard model. BOR best overall response, CI confidence interval, CR complete response, ECOG PS Eastern Cooperative Oncology Group performance status, GEJ gastroesophageal junction, HER2 human epidermal growth factor receptor type 2, HR hazard ratio, IHC immunohistochemistry, ISH in situ hybridisation, NE not estimable, OS overall survival, PD progressive disease, PR partial response, SD stable disease, T-DXd trastuzumab deruxtecan

Fig. 5

Survival rates of patients requiring dose adjustment and those who experienced grade ≥ 3 AEs after having completed 3 cycles of T-DXd. A OS in patients who experienced AEs that led to dose reduction, postponement or discontinuation of T-DXd under T-DXd treatment, B rwPFS in patients who experienced AEs that led to dose reduction, postponement or discontinuation of T-DXd under T-DXd treatment, C OS in patients who experienced grade ≥ 3 AEs under T-DXd treatment, D rwPFS in patients who experienced grade ≥ 3 AEs under T-DXd treatment. 1 month = 30.4375 days. ^aT-DXd was discontinued within 2 cycles. The median (95% CI) time was determined using the Brookmeyer and Crowley method. AE adverse event, CI confidence interval, OS overall survival, rwPFS real-world progression-free survival, T-DXd trastuzumab-deruxtecan