FDA Approves Trastuzumab Deruxtecan for HER2+ Metastatic Gastric/GEJ Cancer

January 15, 2021
Kristi Rosa
Kristi Rosa

Managing Editor, OncLive®
Kristi Rosa joined MJH Life Sciences in 2016 and has since held several positions within the company. She helped launch the rapidly growing infectious disease news resource Contagion, strengthened the Rare Disease Report, of HCPLive, and now serves as the main digital news writer for OncLive. Prior to working at the company, she served as lead copywriter and marketing coordinator at The Strand Theater. Email: krosa@onclive.com

January 15, 2021- The FDA has approved fam-trastuzumab deruxtecan-nxki for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a previous trastuzumab-based regimen.

The FDA has approved fam-trastuzumab deruxtecan-nxki for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a previous trastuzumab (Herceptin)-based regimen.1

The regulatory decision was based on data from the phase 2 DESTINY-Gastric01 trial (NCT04014075), which demonstrated that treatment with the ADC resulted in an improvement in overall survival (OS) compared with irinotecan or paclitaxel, at 12.5 months (95% CI, 9.6-14.3) versus 8.4 months (95% CI, 6.9-10.7), respectively, in patients with advanced, HER2-positive gastric or GEJ adenocarcinoma who had progressed following a trastuzumab-based treatment (HR, 0.59; 95% CI, 0.39-0.88; P = .0097).2

Trastuzumab deruxtecan also elicited a higher objective response rate (ORR) compared with chemotherapy, with a confirmed ORR of 40.5% (95% CI, 31.8%-49.6%) versus 11.3% (95% CI, 4.7%-21.9%), respectively. Additionally, the median progression-free survival (PFS) in the investigative and control arms was 5.6 months (95% CI, 4.3-6.9) versus 3.5 months (95% CI, 2.0-4.3), respectively. The median duration of response (DOR) with the ADC was 11.3 months (95% CI, 5.6–not reached) versus just 3.9 months (95% CI, 3.0-4.9) with chemotherapy.

In the open-label, multicenter, randomized phase 2 DESTINY-Gastric01, investigators evaluated the use of the ADC versus physician’s choice of standard chemotherapy in patients with HER-expressing advanced gastric or GEJ adenocarcinoma who had received at least 2 previous regimens, including fluoropyrimidine, a platinum-based agent, and trastuzumab or approved biosimilar.

The trial enrolled 188 patients who were randomized to receive either trastuzumab deruxtecan (n = 126) or chemotherapy (n = 62). Eighty-six percent of participants received prior treatment with a taxane, 71% had ramucirumab (Cymraza), and 31% received PD-1/PD-L1 inhibitors. At the November 8, 2019 data cutoff date, 22.4% of patients on the investigational arm were still receiving treatment compared with 4.8% of those on the control arm.

The primary end point of the trial was ORR per independent central review (ICR), while secondary end points comprised OS, DOR, PFS, confirmed ORR, and safety.

Earlier data from the trial presented during the 2020 ASCO Virtual Scientific Program showed that the ORR per independent central review (ICR) was substantially higher with the ADC versus chemotherapy, at 51.3% (n = 61; 95% CI, 41.9%-60.5%; P <.0001) and 14.3% (95% CI, 6.4%-26.2%), respectively. The complete response (CR) rate was 8.4% on the trastuzumab deruxtecan arm; no CRs were reported on the chemotherapy arm.

The confirmed ORR per ICR was 42.9% (n = 51; 95% CI, 33.8-91.5) versus 12.5% (n = 7; 95% CI, 5.2-24.1) with the ADC versus chemotherapy, respectively. Additionally, the confirmed disease control rates in the investigative and control arms were 85.7% (n = 102; 95% CI, 78.1-91.5) and 62.5% (n = 35; 95% CI, 48.5-75.1), respectively.

Additionally, the OS rate at 1 year was 52.1% with the ADC versus 28.9% with chemotherapy; the 6-month OS rates were 80.3% and 66.4%, respectively, in the investigational and control arms. The 1-year PFS rates in the investigational arm was 29.9% versus 0% in the control arm; the 6-month PFS rates were 42.8% and 20.6%, respectively.

Regarding safety, the most frequently observed toxicities included laboratory anemia, leukopenia, neutropenia, lymphocytopenia, thrombocytopenia, nausea, decreased appetite, increased aspartate aminotransferase, and fatigue. Additional toxicities comprised increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, hypokalemia, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia.

Notably, the prescribing information for the agent includes a Boxed Warning regarding risks of interstitial lung disease and embryo-fetal toxicity.


  1. FDA approves fam-trastuzumab deruxtecan-nxki for HER2-positive gastric adenocarcinomas. News release. FDA. January 15, 2021. Accessed January 15, 2021. http://bit.ly/35KBZ8T.
  2. Shitara K, Bang Y-J, Iwasa S, et al. 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). J Clin Oncol. 2020;38(suppl 15):4513). doi:10.1200/JCO.2020.38.15_suppl.4513