University of California Irvine Health, Orange, CA, United States of America.
Moffitt Cancer Center, Tampa, FL, United States of America.
Gynecol Oncol. 2019 Oct;155(1):63-68. doi: 10.1016/j.ygyno.2019.07.010. Epub 2019 Jul 27.
OTL38 is a folate-indole-cyanine green-like conjugate to folate receptor alpha (FRa). The objectives of this prospective trial were to assess the safety and efficacy (sensitivity and positive predictive value (PPV)) of OTL38 for intraoperative imaging during epithelial ovarian cancer surgery.
Patients with suspected ovarian cancer planned for cytoreductive surgery were eligible to receive OTL38. Near-infrared (NIR) imaging was used to visualize target lesions that were evaluated by two blinded pathologists. A modified intent to treat (mITT) population of lesions from all patients who received OTL38-NIR imaging, underwent surgery, and had at least one FRa + target lesion was used to determine sensitivity and PPV. Two generalized linear models, with and without random effects, were employed to estimate sensitivity and PPV.
Forty-four patients were evaluated for safety, and 225 lesions from 29 patients (the mITT population) were evaluated for efficacy. When assuming no correlation of interlesional results within a patient, sensitivity was estimated at 85.93% (95% lower boundary CI = 81.19) and PPV at 88.14% (95% lower boundary CI = 83.59). When controlling for actual correlation of detection among multiple lesions within a single patient (a random effect), sensitivity was estimated at 97.97% (95% lower boundary CI = 87.75) and PPV at 94.93% (95% lower boundary CI = 86.13). A total of 48.3% [14/29, (95% CI 0.29-0.67)] of patients had at least one additional lesion detected by OTL38 alone. Eight patients had mild drug-related adverse events including infusion reaction, nausea, vomiting, and abdominal pain.
OTL38-NIR was safe and efficacious in this phase II study regardless of folate expression levels and merits phase III evaluation.
OTL38 是叶酸吲哚菁绿类似物与叶酸受体α（FRa）的缀合物。本前瞻性试验的目的是评估 OTL38 用于上皮性卵巢癌手术中术中成像的安全性和有效性（敏感性和阳性预测值（PPV））。
疑似卵巢癌的患者有资格接受 OTL38 治疗。近红外（NIR）成像用于可视化目标病变，由两名盲法病理学家进行评估。对接受 OTL38-NIR 成像、接受手术且至少有一个 FRa+目标病变的所有患者的改良意向治疗（mITT）病变人群进行分析，以确定敏感性和 PPV。采用带有和不带有随机效应的两种广义线性模型来估计敏感性和 PPV。
44 名患者接受了安全性评估，29 名患者的 225 个病变（mITT 人群）接受了疗效评估。假设患者内病变之间无相关性时，敏感性估计为 85.93%（95%置信区间下限 CI=81.19），PPV 为 88.14%（95%置信区间下限 CI=83.59）。当控制单个患者中多个病变之间实际检测的相关性（随机效应）时，敏感性估计为 97.97%（95%置信区间下限 CI=87.75），PPV 为 94.93%（95%置信区间下限 CI=86.13）。共有 48.3%（29 例患者中 14 例，95%置信区间 0.29-0.67）的患者至少有一个额外的病变被 OTL38 单独检测到。8 名患者发生轻度与药物相关的不良反应，包括输注反应、恶心、呕吐和腹痛。
无论叶酸表达水平如何，OTL38-NIR 在这项 II 期研究中均安全且有效，值得进行 III 期评估。
