Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer Journal Article
| Authors: | Shitara, K.; van Cutsem, E.; Gümüş, M.; Lonardi, S.; de la Fouchardière, C.; Coutzac, C.; Dekervel, J.; Hochhauser, D.; Shen, L.; Mansoor, W. |
| Article Title: | Trastuzumab Deruxtecan or Ramucirumab plus Paclitaxel in Gastric Cancer |
| Abstract: | BACKGROUND On the basis of phase 2 studies, trastuzumab deruxtecan was approved for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma who had previously received trastuzumab-based therapy. Ramucirumab plus paclitaxel is also a standard second-line treatment option regardless of HER2 status. METHODS We conducted an international, randomized, phase 3 trial comparing second-line trastuzumab deruxtecan at a dose of 6.4 mg per kilogram of body weight with ramucirumab plus paclitaxel in patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma confirmed on tumor biopsy conducted after the patient had progression while receiving trastuzumab-based therapy. The primary end point was overall survival. Secondary end points included progression-free survival, confirmed objective response (complete or partial response lasting ≥4 weeks), disease control, duration of response, and safety. RESULTS Among 494 patients who had undergone randomization, overall survival was significantly longer with trastuzumab deruxtecan than with ramucirumab plus paclitaxel (median, 14.7 vs. 11.4 months; hazard ratio for death, 0.70; 95% confidence interval, 0.55 to 0.90; P=0.004). Significant results were also seen with regard to progression-free survival (hazard ratio for disease progression or death, 0.74; 95% CI, 0.59 to 0.92) and confirmed objective response (in 44.3% of the patients in the trastuzumab deruxtecan group vs. 29.1% of those in the ramucirumab-paclitaxel group). The incidence of drug-related adverse events of any grade was 93.0% with trastuzumab deruxtecan and 91.4% with ramucirumab plus paclitaxel; the incidence of drug-related adverse events of grade 3 or higher was 50.0% and 54.1%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 13.9% of the patients who received trastuzumab deruxtecan (grade 1 or 2 in 33 patients and grade 3 in 1) and in 1.3% of those who received ramucirumab plus paclitaxel (grade 3 in 2 patients and grade 5 in 1). CONCLUSIONS Trastuzumab deruxtecan led to significantly longer overall survival than ramucirumab plus paclitaxel among patients with HER2-positive metastatic gastric cancer or gastroesophageal junction adenocarcinoma. Adverse events were common in both groups. Events of interstitial lung disease or pneumonitis with trastuzumab deruxtecan, a known risk, were mainly low-grade. © 2025 Elsevier B.V., All rights reserved. |
| Keywords: | adult; controlled study; aged; aged, 80 and over; middle aged; major clinical study; overall survival; clinical trial; mortality; cancer growth; drug efficacy; drug safety; heart left ventricle failure; paclitaxel; comparative study; antineoplastic agent; adenocarcinoma; progression free survival; multiple cycle treatment; randomized controlled trial; antineoplastic combined chemotherapy protocols; epidermal growth factor receptor 2; camptothecin; cancer screening; tumor biopsy; pathology; monoclonal antibody; pneumonia; questionnaire; multicenter study; stomach cancer; receptor, erbb-2; interstitial lung disease; phase 3 clinical trial; kaplan meier method; drug therapy; disease control; trastuzumab; stomach neoplasms; disease exacerbation; esophagus tumor; esophageal neoplasms; stomach tumor; esophagogastric junction; progression-free survival; kaplan-meier estimate; antibody conjugate; immunoconjugates; gastroesophageal junction; gastroenterology; hematology/oncology; antibodies, monoclonal, humanized; very elderly; ramucirumab; humans; human; male; female; article; trastuzumab deruxtecan; gastrointestinal tract cancer; treatments in oncology; patient reported outcome questionnaire |
| Journal Title: | New England Journal of Medicine |
| Volume: | 393 |
| Issue: | 4 |
| ISSN: | 15334406 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2025-01-01 |
| Start Page: | 336 |
| End Page: | 348 |
| Language: | English |
| DOI: | 10.1056/NEJMoa2503119 |
| PUBMED: | 40454632 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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