Michel Loren, Jimeno Antonio, Sukari Ammar, Beck J Thaddeus, Chiu Joanne, Ahern Elizabeth, Hilton John, Even Caroline, Zanetta Sylvie, Mekan Sabeen, Patel Jilpa, Wu Tia, Dumbrava Ecaterina E
Memorial Sloan Kettering Cancer Center, New York, New York.
Charles C. Gates Center of Stem Cell Biology, University of Colorado Cancer Center, Aurora, Colorado.
Clin Cancer Res. 2025 Mar 3;31(5):832-838. doi: 10.1158/1078-0432.CCR-24-2523.
Treatment options for advanced head and neck squamous cell carcinoma (HNSCC) previously treated with platinum-based chemotherapy and a PD-1 inhibitor are limited. Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in HNSCC. Sacituzumab govitecan (SG) is a Trop-2-directed antibody-drug conjugate approved for patients with certain previously treated solid tumors.
TROPiCS-03 (NCT03964727) is an open-label, multicohort, phase II study evaluating SG in advanced solid tumors, including HNSCC. Adults with locally advanced or metastatic HNSCC that progressed following platinum-based chemotherapy and anti-PD-(L)1 therapy [given sequentially (either order) or in combination] were administered SG 10 mg/kg on days 1 and 8 of a 21-day cycle. The primary endpoint was the investigator-assessed objective response rate. Secondary endpoints included duration of response, clinical benefit rate, progression-free survival, overall survival, and safety.
Patients (N = 43) received a median of 3 (range, 2-9) prior anticancer regimens. The objective response rate was 16% [95% confidence interval (CI), 7%-31%], with seven confirmed partial responses. The clinical benefit rate was 28% (95% CI, 15%-44%). The median (95% CI) duration of response, progression-free survival, and overall survival were 4.2 (2.6-not reached), 4.1 (2.6-5.8), and 9.0 (7.1-10.5) months, respectively. The most common treatment-emergent adverse events (TEAE) were diarrhea (47%), nausea (47%), and neutropenia (47%). Grade ≥3 TEAE occurred in 58% of patients. Three patients died from TEAE, with one event (septic shock) considered related to SG.
These data demonstrate the clinical potential of Trop-2-directed therapy in managing heavily pretreated patients with advanced HNSCC.
对于先前接受过铂类化疗和PD-1抑制剂治疗的晚期头颈部鳞状细胞癌（HNSCC），治疗选择有限。滋养层细胞表面抗原2（Trop-2）在HNSCC中高表达。戈沙妥珠单抗（SG）是一种靶向Trop-2的抗体药物偶联物，已被批准用于某些先前接受过治疗的实体瘤患者。
TROPiCS-03（NCT03964727）是一项开放标签、多队列的II期研究，评估SG在包括HNSCC在内的晚期实体瘤中的疗效。在铂类化疗和抗PD-（L）1治疗（序贯或联合使用）后病情进展的局部晚期或转移性HNSCC成人患者，在21天周期的第1天和第8天接受10mg/kg的SG治疗。主要终点是研究者评估的客观缓解率。次要终点包括缓解持续时间、临床获益率、无进展生存期、总生存期和安全性。
患者（N = 43）既往接受抗癌方案的中位数为3（范围2 - 9）。客观缓解率为16%[95%置信区间（CI），7% - 31%]，有7例确认的部分缓解。临床获益率为28%（95%CI，15% - 44%）。缓解持续时间、无进展生存期和总生存期的中位数（95%CI）分别为4.2（2.6 - 未达到）、4.1（2.6 - 5.8）和9.0（7.1 - 10.5）个月。最常见的治疗中出现的不良事件（TEAE）为腹泻（47%）、恶心（47%）和中性粒细胞减少（47%）。≥3级TEAE发生在58%的患者中。3例患者死于TEAE，其中1例事件（感染性休克）被认为与SG有关。
这些数据证明了靶向Trop-2治疗在管理先前接受过大量治疗的晚期HNSCC患者中的临床潜力。
