Second-line treatment options for patients with metastatic biliary tract cancer (BTC) whose tumors have been unresponsive to gemcitabine-based therapies are largely lacking. NALIRICC was an open-label, randomized, phase 2 interventional study evaluating the efficacy of nanoliposomal irinotecan (Nal-IRI) in patients with advanced, unresectable, and metastatic cholangiocarcinoma (CCA) and gallbladder cancer (GC). The primary objective of this study was to examine whether the addition of Nal-IRI to 5-fluorouracil (5-FU) plus leucovorin (LV) provided better survival outcomes compared with 5-FU plus LV alone as a second-line treatment for BTC. Results were shared at the 2022 ESMO congress.
Eligible patients were aged >18 years with histologically confirmed metastatic cancer (CCA or GC) who had progressed during first-line treatment with gemcitabine. Arm A participants received Nal-IRI (80 mg/m2) plus 5-FU (2400 mg/m2) and LV (400 mg/m2). Patients in arm B received 5-FU (2400 mg/m2) and LV (400 mg/m2) only. Patients were grouped by primary tumor site, and response was evaluated every 6 weeks. The primary end point was progression-free survival (PFS) assessed up to 42 months after treatment. Secondary end points included overall survival (OS), overall response rate, toxicity/safety, and health-related quality of life (QOL).
A total of 100 patients were assessed across 17 study sites in Germany: 49 patients were randomly assigned to arm A (Nal-IRI) and 51 to arm B (no Nal-IRI). Of the 100 patients, 64 were diagnosed with intrahepatic CCA, 19 with extrahepatic CCA, and 17 with GC.
Median OS in arm A was 6.9 months compared with 8.21 months in arm B. Median PFS was comparable regardless of the inclusion of Nal-IRI: 2.76 months in arm A and 2.3 months in arm B. Significantly more patients receiving Nal-IRI reported ≥3 adverse events (AEs) compared with those who did not receive Nal-IRI (70.8% and 50%, respectively). QOL measurements were comparable in both treatment arms.
The NALIRICC trial did not meet its primary end point in that the addition of Nal-IRI to 5-FU plus LV did not improve OS or PFS. Nal-IRI was also associated with a higher rate of patients with ≥3 AEs, indicating higher toxicity. However, this study indicated that 5-FU plus LV may be a reasonable second-line alternative in patients whose cancers have progressed on standard first-line therapies.
Sources: Vogel A, Wenzel P, Folprecht G, et al. Nal-IRI and 5-FU/LV compared to 5-FU/LV in patients with cholangio- and gallbladder carcinoma previously treated with gemcitabine-based therapies (NALIRICC – AIO-HEP-0116). Ann Oncol. 2022;33(suppl 7):S563-S564.
Vogel A, Wenzel P, Folprecht G, et al. Nal-IRI and 5-FU/LV compared to 5-FU/LV in patients with cholangio- and gallbladder carcinoma previously treated with gemcitabine-based therapies (NALIRICC – AIO-HEP-0116). European Society for Medical Oncology Congress 2022. Abstract 53MO.