Results from a second-line trastuzumab deruxtecan phase 2 study in patients with HER2-positive metastatic gastric or gastroesophageal junction cancer reveal promising response and safety.
Gastric adenocarcinoma is the fifth most commonly diagnosed cancer and the third leading cause of cancer-related mortality globally.1 Many patients are initially diagnosed in the advanced stage, giving patients a poor prognosis and a median overall survival of 10 to 12 months.1 Different genetic alterations can contribute to the development of gastric cancer, among these is a subgroup caused by the overexpression of HER2, which occurs in 15% to 20% of all cases.1 HER2 is a member of the epidermal growth factor receptor family involved in signaling pathways leading to cell growth, proliferation, and differentiation.1 This makes HER2 an attractive target for anticancer therapies in gastric cancer. The DESTINY-Gastric01 phase 2 study was a randomized study that examined the antibody–drug conjugate trastuzumab deruxtecan. In this study, patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) cancer that progressed on ≥2 lines of therapy, including therapy with trastuzumab, were enrolled.
The results from the single-arm, phase 2 DESTINY-Gastric02 trial of trastuzumab deruxtecan were reported at the European Society for Medical Oncology Congress 2021 by Van Cutsem and colleagues. This study is the first second-line study of trastuzumab deruxtecan in Western patients with HER2-positive gastric or gastroesophageal cancer. There were 79 patients from the United States and European Union with centrally confirmed HER2-positive, unresectable, metastatic gastric or GEJ cancer who progressed while on or after receiving trastuzumab-containing first-line therapy in this study. Patients were treated with 6.4 mg/kg trastuzumab deruxtecan intravenously every 3 weeks. The primary study end point was objective response rate (ORR) and secondary study end points were progression-free survival (PFS), safety, and duration of response (DOR).
Participants were treated with trastuzumab deruxtecan for a median of 4.3 months. The median follow-up duration was 5.7 months and the median time to response was 1.4 months. Response rate analysis found that 3 patients had a complete response, and 27 patients had a partial response. The confirmed ORR by independent central review was 38%. Median PFS was 5.5 months, and the median DOR was 8.1 months.
All patients experienced treatment-emergent adverse events (TEAEs) with 40 patients experiencing grade ≥3 TEAEs. The most common TEAEs were nausea, vomiting, and fatigue. Interstitial lung disease grade 1 to 2 occurred in 6 patients, with 1 patient experiencing grade 5 interstitial lung disease. There were 12 patients who had dose discontinuation due to adverse events, whereas 19 had dose reductions and 17 had dose interruptions. Overall, the safety profile was manageable in study participants.
The clinical efficacy found in this study demonstrates second-line trastuzumab deruxtecan is an encouraging therapy for use in patients with metastatic gastric or GEJ cancer.
Source: Van Cutsem E, Di Bartolomeo M, Smyth E, et al. 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. Ann Oncol. 2021;32(suppl_5):S1283-S1346.
Reference
- Palle J, Rochand A, Pernot S, et al. Human epidermal growth factor receptor 2 (HER2) in advanced gastric cancer: current knowledge and future perspectives. Drugs. 2020;80:401-415.