Trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2–expressing salivary gland carcinoma: a pooled analysis of two phase I studies

• Published in: Japanese journal of clinical oncology 2024-04, Vol.54 (4), p.434-443
• Main Authors: Takahashi, Shunji, Bando, Hideaki, Kinoshita, Ichiro, Modi, Shanu, Tsurutani, Junji, Bang, Yung-Jue, Sato, Yuta, Nakatani, Shunsuke, Lee, Caleb, Sugihara, Masahiro, Okuda, Yasuyuki, Iwata, Hiroji
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Camptothecin - analogs & derivatives; Camptothecin - therapeutic use; Carcinoma - drug therapy; Female; Humans; Immunoconjugates - adverse effects; Immunoconjugates - therapeutic use; Male; Middle Aged; Original; Receptor, ErbB-2 - metabolism; Salivary Glands - metabolism; Trastuzumab - adverse effects; Trastuzumab - therapeutic use
• ISSN: 1465-3621; 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyad181

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. Clinical trial information FIH study, NCT02564900; DDI study, NCT03383692 This pooled analysis of two phase I clinical trials indicates the clinical benefits and manageable toxicity of trastuzumab-deruxtecan in HER2-expressing salivary gland carcinoma, a rare malignancy with unmet medical needs.