Division of Oncology/Hematology, Kantonsspital Graubünden, Chur, Switzerland.
Department of Medical Oncology and Comprehensive Cancer Center, University Hospital Basel, Basel, Switzerland.
J Clin Oncol. 2023 Nov 20;41(33):5131-5139. doi: 10.1200/JCO.23.00363. Epub 2023 Aug 17.
The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab.
SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years.
Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response <ypT2 ypN0. Overall survival (OS) was 85% (95% CI, 72 to 92) at 2 years and 81% (95% CI, 67 to 89) at 3 years. Grade 3 and 4 treatment-related adverse events (TRAEs) during neoadjuvant treatment occurred in 42% and 25%, respectively. TRAEs related to adjuvant durvalumab were grade 3 in 5 (11%) and grade 4 in 2 (4%) patients.
The addition of perioperative durvalumab to the standard of care for patients with resectable MIUC results in a high EFS and OS at 2 years.
在肌层浸润性尿路上皮癌（MIUC）的围手术期加入免疫疗法似乎很有前景。SAKK 06/17 研究了在新辅助 gemcitabine/cisplatin（GC）化疗中加入 durvalumab，随后进行根治性手术，并在术后辅助使用 durvalumab 进行检查点抑制。
SAKK 06/17 是一项由研究者发起的、开放性、单臂的 II 期研究，纳入了适合顺铂治疗的、cT2-T4a cN0-1 可切除 MIUC 患者。患者接受 4 个周期的新辅助 GC 联合 4 个周期的 durvalumab（从 GC 周期 2 开始），然后进行根治性手术。术后辅助 durvalumab 治疗 10 个周期。主要终点是 2 年无事件生存（EFS）率。
12 个中心共入组 61 例患者。全分析集包括 57 例患者，54 例（95%）为膀胱癌。中位随访时间为 40 个月。主要终点达到，2 年 EFS 率为 76%（单侧 90%CI[下限]，67%；双侧 95%CI，62%至 85%）。3 年 EFS 率为 73%（95%CI，59%至 83%）。在可切除的患者（N=52）中，17 例（33%）达到完全病理缓解，31 例（60%）病理缓解<ypT2ypN0。2 年和 3 年的总生存（OS）率分别为 85%（95%CI，72%至 92%）和 81%（95%CI，67%至 89%）。新辅助治疗期间，3 级和 4 级治疗相关不良事件（TRAEs）发生率分别为 42%和 25%。与辅助 durvalumab 相关的 TRAEs 分别为 5 例（11%）3 级和 2 例（4%）4 级。
在可切除 MIUC 患者的标准治疗中加入围手术期 durvalumab 可显著提高 2 年时的 EFS 和 OS。
