Primary and Updated Analyses for DESTINY-Gastric02 Study: Trastuzumab Deruxtecan Continues to Demonstrate Benefit in Metastatic Gastric and Gastro-oesophageal Cancer

July 17, 2023

Human Epidermal Growth receptor 2 (HER2) is a protein involved in normal cell growth, found in small amounts in almost all human cells, including stomach (gastric) cells. Sometimes, a random change within cancer cells can result in too many copies or over-expression of HER2 on the cell surface. Gastric cancer cells with high levels of HER2 are considered HER2 positive (HER2+), with close to 15–20% of advanced gastric and gastro-oesophageal junction cancers overexpressing HER2, evaluating HER2 status can serve as an important biomarker and therapeutic target for treating gastric cancer.

The recent publication of a study led by our co-founder Prof. Eric Van Cutsem, reports primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in Europe and the USA.

The DESTINY-Gastric02 study was conducted in a Western patient population (Belgium, Spain, Italy, the UK and USA), primarily to confirm the positive results from the DESTINY-Gastric01 study, which comprised of an exclusively Asian population.DESTINY-Gastric02 (NCT04014075) began with the aim of finding out if trastuzumab deruxtecan is safe and works for a Western patient population with gastric or gastroesophageal junction cancer, in patients who have human epidermal growth factor receptor 2 (HER2)-positive gastric or gastro-esophageal junction (GEJ) cancer: that cannot be surgically removed, that has moved to other parts of the body or that got worse during or after treatment that included trastuzumab.

The most recent publication is a longer follow-up of the data from phase 2 of the study showed that trastuzumab deruxtecan continued to show a clinical benefit, with a tolerable safety profile for patients with HER2+ locally advanced or metastatic gastric or GEJ adenocarcinoma who previously received treatment with trastuzumab (Herceptin).1

As previously reported, in the primary analysis publication the baseline characteristics of this nonrandomized phase 2 study consisted of a population of 79 patients, with a median age of 60.7 years, with the median time since diagnosis being 14.2 months. 86.1% of patients had HER2 expression of disease with IHC 3+, 12.7% had IHC 2+/ISH+ and 1.3% were non-evaluable. The study population consisted of 34.2% of patients with gastric cancer and 65.8% with GEJ, and most patients had two or more metastatic site (93.7%).2

The data update shared from the date of cut-off (November 8, 2021) revealed that of the 79 patients in the study, 76 (96.2%) had received one prior line of therapy, while the remaining three (3.8%) had received two lines of therapy. The median follow-up duration of 10.2 months had 10 patients (12.7%) still on treatment. The median treatment duration was 4.3 months (07-22.1). It is important to note that all patients experienced treatment-emergent adverse events (TEAE) grade ≥1, 55.7% reported grade ≥3, with the most common TEAEs being nausea (67.1%), vomiting (44.3%) and fatigue (57.0%).

The new survival data showed overall survival (OS) of 12.1 months ((95% CI, 9.4-15.4), with a median progression-free survival (PFS) of 5.6 months (95% CI, 4.2-8.3) in patients who received trastuzumab deruxtecan.

Of particular interest to patients, and the patient advocacy community, patient-reported outcomes were also presented, highlighting that patient-reported quality of life did not worsen through cycle seven (duration of treatment 4.8 months). The study utilized the European Organization for Research and Treatment of Cancer 5-dimensional (EQ-5D) survey and the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) measure.3

These meaningful results led to the approval of Trastuzumab deruxtecan as a second-line treatment in Europe for patients with HER2-positive advanced gastric Cancer in December of 2022.


  1. Shitara K, Bang YJ, Iwasa S, et al; DESTINY-Gastric01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive gastric cancer. N Engl J Med. 2020;382(25):2419-2430.
  2. LBA55 Primary analysis of a phase II single-arm trial of trastuzumab deruxtecan (T-DXd) in western patients (Pts) with HER2-positive (HER2+) unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer who progressed on or after a trastuzumab-containing regimen, van Cutsem, E. et al. Annals of Oncology, Volume 32, S1332.
  3. Van Cutsem, Eric et al. Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study. The Lancet Oncology, Volume 24, Issue 7, 744 – 756.
Natasha Muench

In order to facilitate the use of our website, we use cookies.

Please confirm if you accept our tracking cookies. When declining the cookies, you can continue visiting the website without sending data to third party services. Read our complete cookie statement here.