Chae Young Kwang, Corthell Lucy, Patel Sandip Pravin, Edwards Robert, Scalici Jennifer M, Kim Hye Sung, Chung Liam Il-Young, Othus Megan, McLeod Christine M, Chen Helen X, Sharon Elad, Streicher Howard, Ryan Christopher W, Blanke Charles D, Kurzrock Razelle
Northwestern University, Chicago, Illinois.
SWOG Statistics and Data Management Center, Seattle, Washington.
Clin Cancer Res. 2025 Jan 17;31(2):308-315. doi: 10.1158/1078-0432.CCR-24-1957.
Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) trial presents initial results of ipilimumab/nivolumab in vulvar cancers.
DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II clinical trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR; confirmed complete response and partial response (PR)] per RECISTv1.1, whereas progression-free survival (PFS), overall survival, clinical benefit rate (CBR; ORR plus stable disease ≥6 months), and toxicity were secondary endpoints.
Sixteen evaluable patients (median age, 55.5 years; 0-6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. The ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); the PFS was 34.1, 16.7. 15.5, 7.2, and 7.0 months for these five patients, respectively. The median PFS and overall survival were 2.2 and 7.6 months, respectively. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n = 4 each). Grade 3 to 4 adverse events occurred in 25% of patients (n = 4). There was one grade 1 to 2 adverse event (6.7%) that led to discontinuation and one (6.7%) grade 5 death adverse event.
Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in 3 of 16 patients, all of whom had durable responses lasting over 1 year. Notably, two additional patients experienced durable stable disease and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.
双重PD - 1/CTLA - 4抑制在多种恶性肿瘤中显示出前景。SWOG S1609双重抗CTLA - 4和抗PD - 1阻断剂用于罕见肿瘤（DART）试验展示了伊匹木单抗/纳武单抗在外阴癌中的初步结果。
DART是一项前瞻性/开放标签/多中心（美国1016个地点）/多队列的II期临床试验，使用伊匹木单抗（每6周静脉注射1mg/kg）加纳武单抗（每2周静脉注射240mg）。主要终点是根据RECISTv1.1标准的客观缓解率[ORR；确认的完全缓解和部分缓解（PR）]，而无进展生存期（PFS）、总生存期、临床获益率（CBR；ORR加疾病稳定≥6个月）和毒性是次要终点。
分析了16例可评估患者（中位年龄55.5岁；0 - 6次既往治疗；无既往免疫治疗），所有患者均为鳞状细胞癌组织学类型。ORR为18.8%（3/16），CBR为25%（4/16），CBR加未确认的PR率为31%（5/16）；这5例患者的PFS分别为34.1、16.7、15.5、7.2和7.0个月。中位PFS和总生存期分别为2.2个月和7.6个月。最常见的不良事件是腹泻、疲劳、瘙痒、厌食和恶心（各25%，n = 4）。25%的患者（n = 4）发生3 - 4级不良事件。有1例1 - 2级不良事件（6.7%）导致停药，1例5级死亡不良事件（6.7%）。
伊匹木单抗加纳武单抗用于外阴癌使16例患者中的3例出现客观缓解，所有缓解均持续超过1年。值得注意的是，另外2例患者经历了持久的疾病稳定和未确认的PR。确定反应和耐药标志物的相关研究正在进行中。
