DESTINY-Gastric01
DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01]
Phase 2N = 187NCT03329690
- Population
- Centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed during at least two previous therapies, including trastuzumab.
- Design
- Open-label randomised phase 2 trial: patients were randomly assigned 2:1 to trastuzumab deruxtecan 6.4 mg/kg every 3 weeks or physician's choice of chemotherapy (irinotecan or paclitaxel). Primary endpoint: objective response by independent central review. Secondary endpoints included overall survival, response duration, progression-free survival, confirmed response and safety. 187 patients were treated (125 and 62).
- Primary endpoint
- ORR
- Arms
- Physician's choice of chemotherapy (control, n = 62): Irinotecan (55 patients) or paclitaxel (7 patients)
- Trastuzumab deruxtecan (experimental, n = 125): Trastuzumab deruxtecan 6.4 mg per kilogram of body weight every 3 weeks
- People
- Shitara K, DESTINY-Gastric01 Investigators
Δ ORR+37 pointsOSHR 0.59 (95% CI 0.39–0.88)Δ median OS+4.1 months
Show the numbers
| Endpoint | Analysis | Trastuzumab deruxtecan | Physician's choice of chemotherapy | Effect |
|---|---|---|---|---|
| ORRAs reported for the 187 treated patients (125 trastuzumab deruxtecan, 62 physician's choice); the abstract does not name the analysis setObjective response by independent central review | primaryShitara 2020 | 51% | 14% | P<0.001 |
| OSAs reported for the 187 treated patients (125 trastuzumab deruxtecan, 62 physician's choice); the abstract does not name the analysis set | primaryShitara 2020 | median 12.5 months | median 8.4 months | HR 0.59 (95% CI 0.39–0.88)P=0.01Overall survival was a secondary endpoint; the abstract states P=0.01 crossed the prespecified O'Brien-Fleming boundary of 0.0202 (based on number of deaths). Trastuzumab deruxtecan-related interstitial lung disease or pneumonitis in 12 patients (grade 1 or 2 in 9, grade 3 or 4 in 3); one drug-related death (pneumonia). |
| Endpoint | Analysis | Trastuzumab deruxtecan | Physician's choice of chemotherapy | Effect |
|---|---|---|---|---|
| ORRAs reported for the 187 treated patients (125 trastuzumab deruxtecan, 62 physician's choice); the abstract does not name the analysis setObjective response by independent central review | primaryShitara 2020 | 51% | 14% | P<0.001 |
| OSAs reported for the 187 treated patients (125 trastuzumab deruxtecan, 62 physician's choice); the abstract does not name the analysis set | primaryShitara 2020 | median 12.5 months | median 8.4 months | HR 0.59 (95% CI 0.39–0.88)P=0.01Overall survival was a secondary endpoint; the abstract states P=0.01 crossed the prespecified O'Brien-Fleming boundary of 0.0202 (based on number of deaths). Trastuzumab deruxtecan-related interstitial lung disease or pneumonitis in 12 patients (grade 1 or 2 in 9, grade 3 or 4 in 3); one drug-related death (pneumonia). |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| OS | 0.59 | 0.39–0.88 |
- Trastuzumab deruxtecan (experimental)
- Physician's choice of chemotherapy (control)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Trastuzumab deruxtecan | Physician's choice of chemotherapy |
|---|---|---|
| 0 | 100.0% | 100.0% |
| 8 | 64.2% | 51.7% |
| 16 | 41.2% | 26.7% |
| 23 | 27.9% | 15.0% |
| 31 | 17.9% | 7.7% |