Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer
| Autor: | Kohei Shitara, Hisato Kawakami, Jeeyun Lee, DESTINY-Gastric Investigators, Hyun-Cheol Chung, Akihito Kojima, Daisuke Sakai, Min-Hee Ryu, Masahiro Sugihara, Kensei Yamaguchi, Hiroshi Yabusaki, Satoru Iwasa, Takahiro Kamio, Naotoshi Sugimoto, Yung-Jue Bang, Yoshinori Kawaguchi, Kaku Saito |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male Immunoconjugates Esophageal Neoplasms Paclitaxel Receptor ErbB-2 Antineoplastic Agents Adenocarcinoma 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Irinotecan 03 medical and health sciences 0302 clinical medicine Bone Marrow Stomach Neoplasms Trastuzumab Humans Medicine 030212 general & internal medicine skin and connective tissue diseases Receptor neoplasms Aged Aged 80 and over biology Tetrapeptide business.industry Cancer General Medicine Middle Aged medicine.disease Survival Analysis Monoclonal Cancer research biology.protein Camptothecin Female Antibody Lung Diseases Interstitial business Previously treated medicine.drug Conjugate |
| Zdroj: | New England Journal of Medicine. 382:2419-2430 |
| ISSN: | 1533-4406 0028-4793 0332-9690 |
| DOI: | 10.1056/nejmoa2004413 |
| Popis: | Trastuzumab deruxtecan (DS-8201) is an antibody-drug conjugate consisting of an anti-HER2 (human epidermal growth factor receptor 2) antibody, a cleavable tetrapeptide-based linker, and a cytotoxic topoisomerase I inhibitor. The drug may have efficacy in patients with HER2-positive advanced gastric cancer.In an open-label, randomized, phase 2 trial, we evaluated trastuzumab deruxtecan as compared with chemotherapy in patients with HER2-positive advanced gastric cancer. Patients with centrally confirmed HER2-positive gastric or gastroesophageal junction adenocarcinoma that had progressed while they were receiving at least two previous therapies, including trastuzumab, were randomly assigned in a 2:1 ratio to receive trastuzumab deruxtecan (6.4 mg per kilogram of body weight every 3 weeks) or physician's choice of chemotherapy. The primary end point was the objective response, according to independent central review. Secondary end points included overall survival, response duration, progression-free survival, confirmed response (response persisting ≥4 weeks), and safety.Of 187 treated patients, 125 received trastuzumab deruxtecan and 62 chemotherapy (55 received irinotecan and 7 paclitaxel). An objective response was reported in 51% of the patients in the trastuzumab deruxtecan group, as compared with 14% of those in the physician's choice group (P0.001). Overall survival was longer with trastuzumab deruxtecan than with chemotherapy (median, 12.5 vs. 8.4 months; hazard ratio for death, 0.59; 95% confidence interval, 0.39 to 0.88; P = 0.01, which crossed the prespecified O'Brien-Fleming boundary [0.0202 on the basis of number of deaths]). The most common adverse events of grade 3 or higher were a decreased neutrophil count (in 51% of the trastuzumab deruxtecan group and 24% of the physician's choice group), anemia (38% and 23%, respectively), and decreased white-cell count (21% and 11%). A total of 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), as adjudicated by an independent committee. One drug-related death (due to pneumonia) was noted in the trastuzumab deruxtecan group; no drug-related deaths occurred in the physician's choice group.Therapy with trastuzumab deruxtecan led to significant improvements in response and overall survival, as compared with standard therapies, among patients with HER2-positive gastric cancer. Myelosuppression and interstitial lung disease were the notable toxic effects. (Funded by Daiichi Sankyo; DESTINY-Gastric01 ClinicalTrials.gov number, NCT03329690.). |
| Databáze: | OpenAIRE |
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