比利时鲁汶大学医院Ignace Vergote团队研究了替索妥单抗-维多汀作为复发性宫颈癌二线或三线治疗的效果。这一研究成果发表在2024年7月4日出版的《新英格兰医学杂志》上。

复发性宫颈癌是一种危及生命的疾病，当一线联合治疗后出现疾病进展时，可用的治疗选择有限。

研究组对复发性或转移性宫颈癌症患者进行了一项临床3期、多国、开放性试验，将替索妥单抗-维多汀作为二线或三线治疗。患者以1:1的比例被随机分配接受替索妥单抗-维多汀单药治疗（每3周每公斤体重2.0 mg）或研究者选择的化疗（拓扑替康、长春瑞滨、吉西他滨、伊立替康或培美曲塞）。主要终点是总生存期。

共有502名患者接受了随机分组（253名患者被分配到替索妥单抗-维多汀组，249名患者被分到化疗组）；两组在人口统计学和疾病特征方面相似。替索妥单抗-维多汀组的中位总生存期明显长于化疗组（11.5个月[95%置信区间{CI}，9.8-14.9]vs.9.5个月[95%CI，7.9-10.7]），结果表明，替索妥单抗-维多汀的死亡风险比化疗低30%（危险比0.70；95%CI，0.54-8.89；双侧P=0.004）。

替索妥单抗-维多汀组的中位无进展生存期为4.2个月（95%可信区间，4.0至4.4），化疗组为2.9个月（95%CI，2.6至3.1；危险比，0.67；95%CI，0.54至0.82；双侧P<0.001）。替索妥单抗-维多汀组和化疗组的客观有效率分别为17.8%和5.2%（优势比4.0；95%可信区间2.1至7.6；双侧P＜0.001）。替索妥单抗-维多汀组和化疗组中总共98.4%的患者在治疗期间（定义为从第1剂第1天到最后一剂后30天的期间）发生了至少一次不良事件；3级或以上事件发生率分别为52.0%和62.3%。共有14.8%的患者因毒性作用而停止接受替索妥单抗-维多汀治疗。

研究结果表明，在复发性宫颈癌症患者中，替索妥单抗-维多汀二线或三线治疗的疗效显著高于化疗。

附：英文原文

Title: Tisotumab Vedotin as Second- or Third-Line Therapy for Recurrent Cervical Cancer

Author: Ignace Vergote, Antonio González-Martín, Keiichi Fujiwara, Elsa Kalbacher, Andrea Bagaméri, Sharad Ghamande, Jung-Yun Lee, Susana Banerjee, Fernando Cotait Maluf, Domenica Lorusso, Kan Yonemori, Els Van Nieuwenhuysen, Luis Manso, Linn Woelber, Anneke Westermann, Allan Covens, Kosei Hasegawa, Byoung-Gie Kim, Miriam Raimondo, Maria Bjurberg, Felipe Melo Cruz, Antoine Angelergues, David Cibula, Lisa Barraclough, Ana Oaknin, Christine Gennigens, Leo Nicacio, Melinda Siew Leng Teng, Elizabeth Whalley, Ibrahima Soumaoro, Brian M. Slomovitz

Issue&Volume: 2024-07-04

Abstract:

BACKGROUND

Recurrent cervical cancer is a life-threatening disease, with limited treatment options available when disease progression occurs after first-line combination therapy.

METHODS

We conducted a phase 3, multinational, open-label trial of tisotumab vedotin as second- or third-line therapy in patients with recurrent or metastatic cervical cancer. Patients were randomly assigned, in a 1:1 ratio, to receive tisotumab vedotin monotherapy (2.0 mg per kilogram of body weight every 3 weeks) or the investigator’s choice of chemotherapy (topotecan, vinorelbine, gemcitabine, irinotecan, or pemetrexed). The primary end point was overall survival.

RESULTS

A total of 502 patients underwent randomization (253 were assigned to the tisotumab vedotin group and 249 to the chemotherapy group); the groups were similar with respect to demographic and disease characteristics. The median overall survival was significantly longer in the tisotumab vedotin group than in the chemotherapy group (11.5 months [95% confidence interval {CI}, 9.8 to 14.9] vs. 9.5 months [95% CI, 7.9 to 10.7]), results that represented a 30% lower risk of death with tisotumab vedotin than with chemotherapy (hazard ratio, 0.70; 95% CI, 0.54 to 0.89; two-sided P=0.004). The median progression-free survival was 4.2 months (95% CI, 4.0 to 4.4) with tisotumab vedotin and 2.9 months (95% CI, 2.6 to 3.1) with chemotherapy (hazard ratio, 0.67; 95% CI, 0.54 to 0.82; two-sided P<0.001). The confirmed objective response rate was 17.8% in the tisotumab vedotin group and 5.2% in the chemotherapy group (odds ratio, 4.0; 95% CI, 2.1 to 7.6; two-sided P<0.001). A total of 98.4% of patients in the tisotumab vedotin group and 99.2% in the chemotherapy group had at least one adverse event that occurred during the treatment period (defined as the period from day 1 of dose 1 until 30 days after the last dose); grade 3 or greater events occurred in 52.0% and 62.3%, respectively. A total of 14.8% of patients stopped tisotumab vedotin treatment because of toxic effects.

CONCLUSIONS

In patients with recurrent cervical cancer, second- or third-line treatment with tisotumab vedotin resulted in significantly greater efficacy than chemotherapy.

DOI: NJ202407043910109

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2313811