Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2–expressing salivary gland carcinoma: A pooled analysis of two phase I studies Journal Article
| Authors: | Takahashi, S.; Bando, H.; Kinoshita, I.; Modi, S.; Tsurutani, J.; Bang, Y. J.; Sato, Y.; Nakatani, S.; Lee, C.; Sugihara, M.; Okuda, Y.; Iwata, H. |
| Article Title: | Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2–expressing salivary gland carcinoma: A pooled analysis of two phase I studies |
| Abstract: | Background: HER2-expressing salivary gland carcinoma (SGC) is associated with poor prognosis. Trastuzumab deruxtecan (T-DXd, DS-8201) has shown evidence of antitumor activity for several HER2-expressing solid tumors in multiple studies. This study aimed to present the efficacy and safety of T-DXd in patients with HER2-expressing SGC from a pooled analysis. Methods: Patients with HER2-expressing SGC were pooled from two phase I, open-label studies of T-DXd: a two-phase, multiple-dose, first-in-human study (NCT02564900) and a single-sequence crossover drug–drug interaction study (NCT03383692). Endpoints included efficacy (objective response rate [ORR], duration of response [DoR] and progression-free survival [PFS]) and safety. Results: This pooled analysis included 17 patients with SGC (median age: 57 years; male: 88.2%); median (range) follow-up duration was 12.0 (2.3–34.8) months. Among these patients, 14 had received prior HER2-targeted agents and 13 had undergone prior radiotherapy. The investigator-assessed confirmed ORR was 58.8% (95% confidence interval [CI], 32.9–81.6). The median (95% CI) DoR and PFS were 17.6 months (4.0 to not evaluable [NE]) and 20.5 months (11.1–NE), respectively. All 17 patients reported treatment-emergent adverse events (TEAEs); 76.5% reported TEAEs of grade ≥3. The most common TEAEs were decreased appetite (94.1%), nausea (88.2%) and neutrophil count decreased (76.5%). Of the 17 patients, five (29.4%) reported adjudicated drug-related interstitial lung disease (grade 1, n = 3; grade 2, n =1; grade 3, n = 1). Conclusion: The results of this pooled analysis provide evidence that clinical benefit is achievable with T-DXd in patients with HER2-expressing SGC. © The Author(s) 2024. Published by Oxford University Press. |
| Keywords: | immunohistochemistry; adult; controlled study; aged; middle aged; major clinical study; drug tolerability; drug efficacy; drug safety; drug withdrawal; solid tumor; outcome assessment; follow up; metabolism; progression free survival; breast cancer; nausea; epidermal growth factor receptor; epidermal growth factor receptor 2; camptothecin; monoclonal antibody; in situ hybridization; pancreatitis; carcinoma; muscle weakness; receptor, erbb-2; salivary gland; salivary glands; phase 1 clinical trial; trastuzumab; crossover procedure; salivary gland carcinoma; meta analysis; human epidermal growth factor receptor 2; itraconazole; drug interaction; non small cell lung cancer; erbb2 protein, human; decreased appetite; antibody conjugate; immunoconjugates; ritonavir; trastuzumab emtansine; antibodies, monoclonal, humanized; high throughput sequencing; cholangitis; humans; human; male; female; article; loss of appetite; trastuzumab deruxtecan; ds8201-a-a104; ds8201-a-j101 |
| Journal Title: | Japanese Journal of Clinical Oncology |
| Volume: | 54 |
| Issue: | 4 |
| ISSN: | 0368-2811 |
| Publisher: | Oxford University Press |
| Date Published: | 2024-04-01 |
| Start Page: | 434 |
| End Page: | 443 |
| Language: | English |
| DOI: | 10.1093/jjco/hyad181 |
| PUBMED: | 38231777 |
| PROVIDER: | scopus |
| PMCID: | PMC10999761 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
