In the primary analysis of the phase II DESTINY-Gastric02 trial, fam-trastuzumab deruxtecan-nxki (T-DXd) produced clinically meaningful and durable responses in Western patients with advanced HER2-positive gastric or gastroesophageal junction cancers whose disease had progressed after a trastuzumab-containing regimen, as reported at the European Society for Medical Oncology (ESMO) Congress 2021 by Eric Van Cutsem, MD, PhD, Professor and Division Head of Digestive Oncology at the University Hospital Gasthuisberg in Leuven, Belgium (Abstract LBA55).
“DESTINY-Gastric02 provides clinical evidence for T-DXd as a valuable second-line HER2-targeted treatment option and supports the ongoing randomized phase III trial, DESTINY-Gastric04,” Dr. Van Cutsem said.
Eric Van Cutsem, MD, PhD
DESTINY-Gastric02 is the follow-up study to DESTINY-Gastric01, which evaluated T-DXd in the third line or later in Asian patients. The objective response was 51% with T-DXd vs 14% with treatment of physician’s choice (P < .001). Overall survival was significantly improved, from 8.4 months to 12.5 months with T-DXd (hazard ratio [HR] = 0.59, P = .01).
“DESTINY-Gastric02 is the first study focused only on second-line T-DXd monotherapy in Western patients with HER2-positive disease [that has] progressed on a trastuzumab-containing regimen,” Dr. Van Cutsem said.
About DESTINY-Gastric02
The nonrandomized phase II study enrolled 79 patients from Europe and the United States who had progressed on one trastuzumab-containing regimen. Patients had a median age of 61, HER2 expression of mostly 3+ (86%), and primarily gastroesophageal junction cancer (66%)—which is more common than gastric cancer in Western populations. Almost all patients had at least two metastatic sites, including the liver in 63%.
Patients were retested for HER2 positivity before being treated with T-DXd at 6.4 mg/kg every 3 weeks. The primary endpoint was confirmed response by independent central review.
Thirty patients responded, yielding an objective response rate of 38.0% by independent central review. Three patients (3.8%) had complete responses. “The waterfall plot shows that the majority of patients had some tumor regression,” Dr. Van Cutsem noted.
At a median follow-up of 5.7 months, the median duration of response was 8.1 months and median progression-free survival was 5.5 months.
KEY POINTS
- T-DXd produced responses in 38% of patients, including complete responses in almost 4%.
- Adjudicated interstitial lung disease was observed in 7.6% of patients, with all but one case classified as mild.
Safety Summary
The median duration of treatment was 4.3 months. The most common treatment-related adverse events associated with discontinuation of the drug were investigator-reported pneumonitis (3.8%) and interstitial lung disease (2.5%). The most common drug-related toxicities associated with dose reduction were nausea (7.6%) and decreased neutrophil count (5.1%), Dr. Van Cutsem reported.
Grade ≥ 3 treatment-related adverse events were observed in 26.6% of patients, consisting primarily of nausea, fatigue, anemia, and decreased neutrophil count.
Adjudicated drug-related interstitial lung disease occurred in 6 of 79 (7.6%) patients and was of grade 1 or 2 in all but one patient. Median time to onset of this toxicity was 80.5 days (range = 53–85 days), with a median duration of 38 days (range = 15–142 days).
“The safety profile was generally consistent with the established safety profile of T-DXd,” he said.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
