Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer
- Study type
- Clinical trial
- Study name
- DESTINY-Gastric01
- Phase
- Phase 2
- Design
- Open-label randomised phase 2 trial with 2:1 randomisation
- Sample size
- 187 treated patients (125 in the trastuzumab deruxtecan group and 62 in the chemotherapy group)
- Source
- N Engl J Med · 2020
- Trial registration
- NCT03329690
In plain words
In this study, the drug trastuzumab deruxtecan was given to people with advanced HER2-positive stomach cancer whose disease had got worse after several earlier treatments, including trastuzumab. Compared with usual chemotherapy, this drug shrank the tumour in a larger share of patients and helped patients live longer. However, low blood counts and inflammation or damage of the lungs (interstitial lung disease) were important side effects, and patients need to be watched closely.
Key results
Treatment arms and regimens
Trastuzumab deruxtecan 6.4 mg/kg IV every 3 weeks. Number of patients: 125.
Physician's choice monotherapy: irinotecan at a starting dose of 150 mg/m² every 2 weeks, or paclitaxel at a starting dose of 80 mg/m² weekly (dose reductions allowed); 55 patients received irinotecan and 7 paclitaxel.
Source of the regimen details: Abstract of the paper (NEJM 2020) and ClinicalTrials.gov NCT03329690 (starting doses of irinotecan and paclitaxel in the physician's choice group)
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with centrally confirmed HER2-positive gastric or gastro-oesophageal junction adenocarcinoma whose disease had progressed while receiving at least two previous therapies, including trastuzumab.
Endpoints
Primary endpoint: objective response by independent central review. Secondary endpoints: overall survival, duration of response, progression-free survival, confirmed response (response lasting at least 4 weeks) and safety.
Safety and side effects
Most common grade 3 or higher adverse events: decreased neutrophil count (51% in the trastuzumab deruxtecan group versus 24% in the chemotherapy group), anaemia (38% versus 23%) and decreased white cell count (21% versus 11%). In total, 12 patients had trastuzumab deruxtecan-related interstitial lung disease or pneumonitis (grade 1 or 2 in 9 patients and grade 3 or 4 in 3 patients), as adjudicated by an independent committee. One drug-related death (from pneumonia) was reported in the trastuzumab deruxtecan group, and no drug-related deaths occurred in the chemotherapy group.
Clinical significance and place in guidelines
According to the abstract, trastuzumab deruxtecan significantly improved response and overall survival compared with standard chemotherapy in previously treated patients with HER2-positive gastric cancer. Close monitoring for myelosuppression and interstitial lung disease is essential. The status of drug approvals and formal clinical guideline recommendations should be checked in up-to-date sources, as the abstract does not address them.
Limitations
This was a phase 2, open-label trial, with a control group of physician's choice chemotherapy (irinotecan or paclitaxel). The number of patients was relatively limited (187 treated patients). The P value for overall survival crossed the prespecified boundary. Other limitations should be checked in the full text.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.