背景：帕夫拉西寧鈉作為視覺刺激的輔助藥物正在研究中通過提供葉酸受體的術中成像進行檢查和觸診陽性（FR+）卵巢癌。由於完全切除（R0）是總生存率的最強有力的預測因素，因此提高病灶檢出率的方法有望被廣泛應用有益於患者結果。
Background: Pafolacianine sodium is under investigation as an adjunct to visual inspection and palpation by providing intra-operative imaging of folate receptor positive (FR+) ovarian cancer. Since complete resection (R0) is the strongest predictor of overall survival, methods to enhance detection of lesions are expected to benefit patient outcomes.
方法：第 3 階段，隨機，多中心，單劑量開放標記關鍵試驗（NCT03180307）在 11 中心計劃接受細胞減滅術的卵巢癌患者中招募，從 2018 年 3 月到 2020 年 4 月在美國和荷蘭進行，研究目的是驗證帕夫拉西寧鈉的有效性和安全性(0.025mg/kg，成像前 1 小時靜脈注射）結合術中近紅外熒光（NIRF）成像用於檢測觸診和正常白光未發現的其他病變。
Methods: For this phase 3, randomized, multicenter, single dose, open-label pivotal trial (NCT03180307), patients with ovarian cancer who were scheduled to undergo cytoreductive surgery were recruited from 11 sites in the US and Netherlands from March 2018 through April 2020. The study objectives were to confirm efficacy and safety of pafolacianine sodium (0.025 mg/kg i.v., ≥1 h prior to imaging) in combination with intraoperative near-infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light alone.
結果：共有 150 例患者服用帕夫拉西寧鈉（安全性分析數據集）；全組 109 例用於療效分析的分析集。患者主要為漿液性腺癌（n=72；68.6%）和晚期疾病（n=83；76.1%). 在 33%的患者（109 例中有 36 例）中，用帕夫拉西寧鈉進行 NIRF 顯像可發現額外的異常未計劃切除且未被正常白細胞檢測到的病變光照和觸診（P<0.001，95%CI[0.243，0.427]）。在那些間期去瘤率較高，為 39.7%（第 23 頁，共 58 頁；95%置信區間 [0.270 ， 0.534] ）。在個體病變水平上 pafolacianine 鈉聯合 NIRF 檢測卵巢癌的敏感性為 83%（95%CI[73.9,89.4]），假陽性率為 32.7%（95%CI）[25.6, 40.7]). 研究者報告 62.4%的患者實現了完全切除（R0）（68/109）的病人。藥物相關不良事件（AE）報告率為 30%病人（150 人中有 45 人）。最常見的藥物相關不良事件是惡心（18.0%）、嘔吐（5.3%）和腹痛（4.7%）。術中輸液反應多為輕中度（96%）；89%在發病後 24 小時內痊愈。無藥物相關的嚴重不良事件或死亡已報告。
Results: Pafolacianine sodium was administered to 150 total patients (safety analysis set); 109 patients comprised the full analysis set for efficacy analyses. Patients had primarily serous adenocarcinoma (n = 72; 68.6%) and advanced stage disease (n = 83; 76.1%). In 33% of patients (36 of 109), NIRF imaging with pafolacianine sodium identified additional lesions that were not planned for resection and were not detected by normal white light and palpation (P< 0.001, 95% CI [0.243, 0.427]). Among patients who underwent interval debulking surgery, the rate was higher, at 39.7% of patients (23 of 58; 95% CI [0.270, 0.534]). At the individual lesion level, the accuracy of pafolacianine sodium with NIRF to detect ovarian cancer is reflected by sensitivity of 83% (95% CI [73.9, 89.4]) and a false positive rate of 32.7% (95% CI [25.6, 40.7]). Investigators reported achieving complete resection (R0) in 62.4% (68 of 109) of patients. Drug-related adverse events (AEs) were reported by 30% of patients (45 out of 150). The most frequently reported drug-related AEs were nausea (18.0%), vomiting (5.3%), and abdominal pain (4.7%). Infusion reactions at the time of the procedure were mostly (96%) mild or moderate in severity; 89% resolved within 24 hours of onset. No drug-related serious AEs or deaths were reported.
結論：帕夫拉西寧鈉與 NIRF 的 3 期試驗影像學達到了其主要終點，術中發現了額外的癌症有統計意義的患者計劃切除。因此，帕夫拉西寧鈉可能為當前的外科影像學提供一種新的實時輔助手段卵巢癌手術方式。
Conclusions: This phase 3 trial of pafolacianine sodium with NIRF imaging met its primary endpoint, intraoperatively identifying additional cancer not planned for resection in a statistically significant number of patients. Therefore, pafolacianine sodium may offer a novel real-time adjunct to current surgical imaging practice in ovarian cancer surgery.
