FDA Approves Irinotecan Liposome For First-line Treatment Of Metastatic Pancreatic Adenocarcinoma
FDA Approves Irinotecan Liposome For First-line Treatment Of Metastatic Pancreatic Adenocarcinoma
On February 13, 2024, the Food and Drug Administration approved irinotecan liposome (Onivyde, Ipsen Biopharmaceuticals, Inc.) with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.
2024年2月13日，美國食品藥品監督管理局批准了含有奧沙利鉑、氟尿嘧啶和亞葉酸的伊立替康脂質體（Onivyde，Ipsen Biopharicals, Inc.），用於轉移性胰腺腺癌的一線治療。
Full prescribing information for Onivyde will be posted here.
Onivyde的完整處方信息將在此處發佈。
Efficacy was evaluated in NAPOLI 3 (NCT04083235), a randomized, multicenter, open-label, active-controlled trial in 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting. Randomization was stratified by region, liver metastases, and ECOG performance status. Patients were randomized (1:1) to receive one of the following treatments:
NAPOLI 3（NCT04083235）是一項隨機、多中心、開放標籤、主動對照試驗，對770名以前未在轉移環境中接受過化療的轉移性胰腺腺癌患者進行了療效評估。隨機分組按區域、肝轉移和心電圖表現狀態進行分層。患者被隨機分配（1:1），接受以下治療之一：
- NALIRIFOX: irinotecan liposome 50 mg/m2 as an intravenous infusion over 90 minutes, followed by oxaliplatin 60 mg/m2 as an intravenous infusion over 120 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks.
- Gem+NabP: Nab-paclitaxel 125 mg/m2 as an intravenous infusion over 35 minutes, followed by gemcitabine 1000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle.
- NALIRIFOX：伊立替康脂質體 50 mg/m2，靜脈輸注超過 90 分鐘，隨後奧沙利鉑靜脈輸注 60 mg/m2，靜脈注射 120 分鐘，然後靜脈注射 400 mg/m2，超過 30 分鐘，氟尿嘧啶 2400 mg/m2，靜脈注射 46 小時，每 2 週一次。
- GEM+NABP：在每28天週期的第1、8和第15天，靜脈注射NAB-紫杉醇 125 mg/m2，靜脈注射 1000 mg/m2，超過 30 分鐘。
The main efficacy outcome measure was overall survival (OS). Additional efficacy measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR). NAPOLI 3 demonstrated a statistically significant improvement in OS and PFS for the NALIRIFOX arm over the Gem+NabP arm. Median OS was 11.1 months (95% CI: 10.0, 12.1) in the NALIRIFOX arm and 9.2 months (95% CI: 8.3, 10.6) in the Gem+NabP arm (Hazard Ratio [HR] 0.84 [95% CI: 0.71, 0.99]; p-value 0.0403). Median PFS was 7.4 months (95% CI: 6.0, 7.7) in the NALIRIFOX arm and 5.6 months (95% CI: 5.3, 5.8) in the Gem+NabP arm (HR 0.70 [95% CI: 0.59, 0.85]; p-value 0.0001). ORR was 41.8% (95% CI: 36.8, 46.9) in the NALIRIFOX arm and 36.2% (95% CI: 31.4, 41.2) in the Gem+NabP arm.
主要療效結果衡量標準是總存活率 (OS)。其他療效指標包括研究者評估的無進展存活率（PFS）和客觀緩解率（ORR）。NAPOLI 3顯示，與GEM+NABP部門相比，NALIRIFOX分支的操作系統和PFS在統計學上取得了顯著的改善。NALIRIFOX分組的操作系統中位數爲11.1個月（95％置信區間：10.0，12.1），GEM+NABP組的操作系統中位數爲9.2個月（95％置信區間：8.3，10.6）（危險比 [HR] 0.84 [95％置信區間：0.71，0.99]；p值0.0403）。NALIRIFOX分組的PFS中位數爲7.4個月（95％置信區間：6.0，7.7），GEM+NABP組的PFS中位數爲5.6個月（95％置信區間：5.3，5.8）（HR 0.70 [95％置信區間：0.59，0.85]；p值0.0001）。NALIRIFOX部門的ORR爲41.8％（95％置信區間：36.8，46.9），GEM+NABP部門的ORR爲36.2％（95％置信區間：31.4，41.2）。
The most common adverse reactions of NALIRIFOX (≥20% with a difference between arms of ≥5% for all grades or ≥2% for Grades 3 or 4 compared to Gem+NabP) were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities (≥10% Grade 3 or 4) were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.
NALIRIFOX最常見的不良反應是腹瀉、疲勞、噁心、嘔吐、食慾減退、食慾減退、腹痛、粘膜發炎、便秘和體重減輕，所有等級的組間差異≥5％，3或4年級不良反應≥2％）。最常見的實驗室異常（≥10％3或4級）是中性粒細胞減少、鉀減少、淋巴細胞減少和血紅蛋白降低。
The recommended irinotecan liposome dose is 50 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Administer irinotecan liposome before oxaliplatin, fluorouracil, and leucovorin. There is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal.
推薦的伊立替康脂質體劑量爲50 mg/m2，靜脈滴注，每 2 周 90 分鐘。在奧沙利鉑、氟尿嘧啶和亞葉酸之前給藥伊立替康脂質體。對於血清膽紅素超過正常上限的患者，沒有推薦劑量的伊立替康脂質體。
This application was granted orphan drug designation.
該申請被認定爲孤兒藥。
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA's MedWatch Reporting System or by calling 1-800-FDA-1088.
醫療保健專業人員應向 FDA 的 MedWatch 報告系統或致電 1-800-FDA-1088 報告所有疑似與使用任何藥物和設備相關的嚴重不良事件。
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE's Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.
如需爲研究性腫瘤學產品的單一患者臨床試驗提供幫助，醫療保健專業人員可以致電 240-402-0004 聯繫OCE的項目促進者或發送電子郵件至 OncProjectFacilitate@fda.hhs.gov。
譯文內容由第三人軟體翻譯。