Background: Second-line chemotherapy with 5-fluorouracil/leucovorin (5FULV) and liposomal irinotecan improves survival in advanced biliary tract cancer (BTC). In this phase 1b/2 trial, we investigated the combination of 5FULV and liposomal irinotecan with nivolumab following progression on first-line chemotherapy for advanced BTC.
Methods: Patients received 2,400 mg/m 5-fluorouracil, leucovorin (dose level: 0:400 or -1:200 mg/m), 70 mg/m liposomal irinotecan, and 240 mg nivolumab every 2 weeks (ClinicalTrials.gov: NCT03785873). The phase 1b and 2 primary objectives included recommended phase 2 dose (RP2D) and median progression-free survival (PFS; null and alternative hypotheses of 2.9 and 5.0 months) with a two-sided alpha of 0.05 and >80% power. Secondary objectives were safety, objective response rate (ORR), and overall survival (OS).
Findings: Of 30 patients with a median age of 63.5 years, 18 (60%) were men, 25 (83%) were White, 16 (53%) had an ECOG performance status of 0, and 19 (63.3%) had intrahepatic cholangiocarcinoma. In phase 1b, the RP2D was dose level 0 after a dose-limiting toxicity event of enterocolitis (n = 1). Median PFS was 4.1 months (95% confidence interval [CI], 1.9-9.9). The ORR was 16.7% (5 partial responses) per irRECIST, the median OS was 7.4 months (95% CI, 5.7-15.9), and the 24-month survival rate was 23.3%. The most common grade ≥3 treatment-related adverse events were diarrhea (5; 16.7%), fatigue (4; 13.3%), and neutropenia (3; 10%).
Conclusions: Treatment was well tolerated, but the primary endpoint was not met. The median OS was similar to prior trials with this drug combination, but the 24-month survival rate was higher than expected.
Funding: This work was funded by Ipsen Biopharmaceuticals, Bristol-Myers Squibb (CA209-8LF), and the University of Michigan Rogel Cancer Center (P30CA046592).
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http://dx.doi.org/10.1016/j.medj.2024.10.024 | DOI Listing |
Macromol Biosci
December 2024
Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals & College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
Irinotecan hydrochloride (CPT-11) is one of the first-line drugs used in the clinical treatment of colorectal cancer (CRC). However, the concomitant adverse effect of delayed diarrhea has hindered its clinical use. CPT-11 combined with Thalidomide (THA) therapy is considered a palliative strategy.
View Article and Find Full Text PDFMed
December 2024
Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA.
J Gastroenterol
November 2024
Department of Gastroenterological, Breast and Endocrine Surgery, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Am J Clin Oncol
November 2024
HM CIOCC MADRID (Centro Integral Oncológico Clara Campal), Hospital Universitario HM Sanchinarro, HM Hospitales.
Objective: To evaluate the efficacy of neoadjuvant chemotherapy combination with liposomal irinotecan, 5-fluorouracil, leucovorin, and oxaliplatin in patients with locally advanced rectal cancer.
Methods: This was a phase 2, nonrandomized, multicenter study in adults with stage II or III rectal cancer and an Eastern Cooperative Oncology Group performance status of 0 to 1. Total neoadjuvant therapy (TNT) consisted of neoadjuvant chemotherapy combination with liposomal irinotecan (60 mg/m2), oxaliplatin (60 mg/m2), leucovorin (400 mg/m2), and fluorouracil (2400 mg/m²), followed by chemoradiotherapy [ie, capecitabine (825 mg/m2) and radiotherapy according to the standard of care].
Int J Pharm
November 2024
Department of Pharmaceutical Sciences and the Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Onivyde® is an intravenous irinotecan liposomal injection approved by the FDA for the treatment of gemcitabine-refractory metastatic adenocarcinoma of the pancreas in combination with fluorouracil and leucovorin. In the Onivyde® formulation, irinotecan is encapsulated in the inner compartment of the liposome using sucrose octasulfate as a trapping agent, and stabilized by a pegylated lipid membrane, resulting in prolonged circulation in the body. Due to its complex formulation design, there is limited information available regarding the critical quality attributes (CQAs) of Onivyde® and suitable methods for evaluating these attributes.
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