维迪西妥单抗联合替雷利珠单抗在膀胱癌新辅助治疗中的疗效和安全性分析

Efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer

目的评估维迪西妥单抗联合替雷利珠单抗在膀胱癌新辅助治疗中的疗效和安全性。方法回顾性分析2022年4月至2023年1月于重庆医科大学附属第一医院接受维迪西妥单抗联合替雷利珠单抗行新辅助治疗的16例膀胱癌患者的临床资料。男15例,女1例;年龄(66.12±14.37)岁。新辅助治疗前影像学评估肿瘤分期T_(2)N_(0)M_(0)期5例,T_(3)N_(0)M_(0)期11例;活检病理为低级别尿路上皮癌3例,高级别尿路上皮癌13例;活检病理免疫组化染色示HER-2(0)、(+)、(++)、(+++)分别为1、6.6、3例。新辅助治疗方案:维迪西妥单抗120mg,每2周为1个周期,共4个周期;替雷利珠单抗200mg,每3周为1个周期,共3个周期。新辅助治疗后行影像学检查评估靶病灶变化情况。分析新辅助治疗的疗效及不良反应。结果16例均完成新辅助治疗。16例中5例完全缓解,7例部分缓解,3例疾病稳定,1例疾病进展。12例(75.0%)客观缓解,15例(93.8%)疾病控制,14例(87.5%)目标病灶较基线缩小。在9例HER-2阳性(++/+++)和7例HER-2阴性(0/+)患者中分别有2例(22.2%)和3例(42.9%)达完全缓解,分别有8例(88.9%)和4例(57.1%)达客观缓解。16例新辅助治疗后,6例拒绝手术治疗,2例行保留膀胱综合治疗;8例行根治性膀胱切除术,手术切缘均为阴性,其中5例(62.5%)术后病理分期<T_(2)期,2例(25.0%)达病理完全缓解。仅2例出现术后相关并发症,均经治疗后好转。新辅助治疗的3~4级不良反应为血糖升高2例(12.5%),ALT升高1例(6.3%),高甘油三酯血症1例(6.3%),白细胞减少1例(6.3%)。免疫相关不良反应包括皮疹3例(18.8%),甲状腺功能减退2例(12.5%),免疫性结肠炎1例(6.3%)。结论维迪西妥单抗联合替雷利珠单抗在膀胱癌的新辅助治疗中客观缓解率和疾病控制率高,严重不良反应发生率低,手术切缘阳性率低,且在HER-2阴性的患者中亦有较好的疗效。

Objective To evaluate the efficacy and safety of disitamab vedotin combined with tislelizumab in the neoadjuvant treatment of bladder cancer.Methods The clinical data of 16 bladder cancer patients who received neoadjuvant therapy with disitamab vedotin combined with tislelizumab from April 2022 to January 2023 at the First Hospital of Chongqing Medical University were retrospectively analyzed.There were 15 males and 1 female,aged(66.12±14.37)years old.The immunohistochemical staining of biopsy pathology showed that HER-2(0),(+),(++),and(+++)were in 1,6,6,and 3 cases,respectively.Before neoadjuvant therapy,5 cases were in T_(2)N_(0)M_(0) stage,and 11 cases were in T_(3)N_(0)M_(0) stage.Biopsy pathology showed 3 cases were low-grade uroepithelial carcinoma,and 13 cases were high-grade uroepithelial carcinoma.Neoadjuvant therapy regimens:Disitamab vedotin 120 mg,every 2 weeks for 1 cycle,a total of 4 cycles.Tislelizumab 200 mg,every 3 weeks for 1 cycle,a total of 3 cycles.Surgery was performed at 2-3 weeks after neoadjuvant therapy.The efficacy and adverse effects of neoadjuvant therapy were analyzed.Results All 16 cases completed neoadjuvant therapy.Five cases achieved complete remission,7 cases achieved partial remission,3 cases had stable disease,and 1 case had disease progression.Twelve cases(75.0%)achieved objective remission,15 cases(93.8%)had disease control,and 14 cases(87.5%)had a reduction in the target lesion from baseline.Complete remission was achieved in 2(22.2%)of 9 HER-2-positive patients and and 3(42.9%)of 7 HER-2-negative patients,respectively,and objective remission was achieved in 8(88.9%)and 4(57.1%).After neoadjuvant treatments,surgical treatments were refused in 6 cases,and bladder-preserving combination therapy was performed in 2 cases.Radical cystectomy were performed in 8 cases,with negative margins for surgical incision,of which 5 cases(62.5%)had postoperative pathologic stage<T2,and 2 cases(25.0%)reached pathological complete remission.Only 2 cases developed postoperative related complications,all of which improved with treatment.Grade 3-4 adverse reactions of neoadjuvant therapy included elevated blood glucose in 2 cases(12.5%),elevated ALT in 1 case(6.3%),hypertriglyceridemia in 1 case(6.3%),and leukopenia in 1 case(6.3%).Immune-related adverse reactions included rash in 3 cases(18.8%),hypothyroidism in 2 cases(12.5%),and immune colitis in 1 case(6.3%).Conclusions In the neoadjuvant treatment of bladder cancer,disitamab vedotin combined with tislelizumab has high objective remission rate and disease control rate,low incidence of serious adverse reactions and high rate of negative surgical margins.It also has better efficacy in HER-2 negative patients.