Trastuzumab deruxtecan in patients in the USA and Europe with HER2-positive advanced gastric or gastroesophageal junction cancer with disease progression on or after a trastuzumab-containing regimen (DESTINY-Gastric02): primary and updated analyses from a single-arm, phase 2 study

• Published in: The lancet oncology 2023-07, Vol.24 (7), p.744-756
• Main Authors: Van Cutsem, Eric, di Bartolomeo, Maria, Smyth, Elizabeth, Chau, Ian, Park, Haeseong, Siena, Salvatore, Lonardi, Sara, Wainberg, Zev A, Ajani, Jaffer, Chao, Joseph, Janjigian, Yelena, Qin, Amy, Singh, Jasmeet, Barlaskar, Ferdous, Kawaguchi, Yoshinori, Ku, Geoffrey
• Format: Article
• Language: English
• Subjects: Adverse events; Aged; Antibodies; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Biopsy; Brain research; Cancer; Cancer therapies; Chemotherapy; Disease Progression; Drug dosages; Drug withdrawal; ErbB-2 protein; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - genetics; Esophagogastric Junction - pathology; Esophagus; FDA approval; Female; Gastric cancer; Humans; Immunoconjugates - adverse effects; Leukocytes (neutrophilic); Lung diseases; Male; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Patients; Pneumonitis; Receptor, ErbB-2 - analysis; Receptor, ErbB-2 - genetics; Solid tumors; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Targeted cancer therapy; Trastuzumab
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(23)00215-2

Approximately 15–20% of advanced gastric and gastro-oesophageal junction cancers overexpress HER2. In DESTINY-Gastric01, the HER2-targeted antibody-drug conjugate trastuzumab deruxtecan improved response and overall survival versus chemotherapy in patients from Japan and South Korea with locally advanced or metastatic HER2-positive gastric or gastro-oesophageal junction cancer whose disease progressed after two lines of previous therapy including trastuzumab. Here, we report primary and updated analyses of the single-arm, phase 2 DESTINY-Gastric02 trial, which aimed to examine trastuzumab deruxtecan in patients living in the USA and Europe. DESTINY-Gastric02 is a single-arm, phase 2 study in adult patients from 24 study sites in the USA and Europe (Belgium, Spain, Italy, and the UK). Eligible patients were aged at least 18 years and had an Eastern Cooperative Oncology Group performance status of 0 or 1, pathologically documented unresectable or metastatic gastric or gastro-oesophageal junction cancer, progressive disease on or after first-line therapy with a trastuzumab-containing regimen, with at least one measurable lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and centrally confirmed HER2-positive disease on a postprogression biopsy. Patients were given 6·4 mg/kg of trastuzumab deruxtecan intravenously every 3 weeks until disease progression, withdrawal by patient, physician decision, or death. The primary endpoint was confirmed objective response rate by independent central review. The primary endpoint and safety were assessed in the full analysis set (ie, participants who received at least one dose of study drug). Here, we report the primary analysis of this study, with a data cutoff of April 9, 2021, and an updated analysis, with a data cutoff of Nov 8, 2021. This trial is registered with ClinicalTrials.gov, NCT04014075, and is ongoing. Between Nov 26, 2019, and Dec 2, 2020, 89 patients were screened and 79 were enrolled and subsequently treated with trastuzumab deruxtecan (median age 60·7 years [IQR 52·0–68·3], 57 [72%] of 79 were male, 22 [28%] were female, 69 [87%] were White, four [5%] were Asian, one [1%] was Black or African American, one [1%] was Native Hawaiian or Pacific Islander, one had missing race, and three [4%] were other races). At the primary analysis (median follow-up 5·9 months [IQR 4·6–8·6 months]), confirmed objective response was reported in 30 (38% [95% CI 27·3–49·6]) of 79 patients, including three (4