Addition of Liposomal Irinotecan to Chemo Improves PFS in Biliary Tract Cancer

Treatment with liposomal irinotecan plus fluorouracil and leucovorin resulted in a significant improvement in progression-free survival (PFS) vs fluorouracil and leucovorin alone in second-line, previously treated metastatic biliary tract cancer, according to data from an updated analysis of the phase 2b NIFTY trial (NCT03524508).

"Treatment with [liposomal irinotecan] plus [fluorouracil/leucovorin] could be considered as an option for patients with previously treated advanced [biliary tract cancer," according to the investigators of the phase 2 NIFTY trial.

In a population of 178 patients, the median PFS by masked independent central review (MICR) was 4.2 months (95% CI, 2.8-5.3) in the irinotecan arm vs 1.7 months (95% CI, 1.4-2.6) in the fluorouracil/leucovorin arm (Hazard ratio [HR], 0.61; 95% CI, 0.44-0.86; P = .004). Additionally, the investigator-assessed PFS in each arm, respectively, was 3.9 months (95% CI, 2.7-5.2) vs 1.6 months (95% CI, 1.3-2.2; HR, 0.51; 95% CI, 0.36-0.71; P <.001). Moreover, the 6-month PFS rate was 31.8% (95% CI, 21.7%-41.8%) vs 15.1% (95% CI, 7.5%-22.7%) in each respective arm.

The median follow-up was 33.2 months, with 12 patients continuing follow-up for survival as of the data cut-off.

“The NIFTY phase 2b randomized clinical trial demonstrated a significant improvement in PFS and OS with treatment with second-line [liposomal irinotecan] plus [fluorouracil/leucovorin] compared with [fluorouracil/leucovorin] alone for patients with advanced [biliary tract cancer] who experienced progression while receiving gemcitabine plus cisplatin,” the investigators wrote. “Treatment with [liposomal irinotecan] plus [fluorouracil/leucovorin] could be considered as an option for patients with previously treated advanced [biliary tract cancer].”

The multicenter, open-label trial took place in 5 tertiary centers across South Korea from September 2018 to December 2021. Patients were eligible to participate if they had histologically or cytologically confirmed advanced biliary tract cancer and were 19 years of age or older. The population also needed to have disease progression by RECIST 1.1 criteria, an ECOG performance status of 0 or 1, and adequate organ function.

Patients were randomly assigned 1:1 to receive either the irinotecan regimen or fluorouracil/leucovorin. Patients were stratified based on primary tumor location, prior surgery with curative intent, and if they were part of a participating center. Patients in the experimental arm (n = 88) received 70 mg/m² of intravenous liposomal irinotecan plus 400 mg/m² of leucovorin and 2400 mg/m² of fluorouracil, and the control arm (n = 86) received the fluorouracil/leucovorin backbone alone.

The study’s primary end point was PFS by MICR, with secondary end points including PFS by investigator assessment, overall survival (OS), safety, and quality of life.

The median patient age was 64 years (interquartile range, 38-84) and 43% of patients were female. Additionally, 43% of patients had intrahepatic cholangiocarcinoma, 27% had extrahepatic cholangiocarcinoma, and 30% had gallbladder cancer.

In terms of additional efficacy findings, the median OS was 8.6 months (95% CI, 5.4-10.5) in the irinotecan arm vs 5.3 months (95% CI, 4.7-7.2) in the fluorouracil/leucovorin arm (HR, 0.68; 95% CI, 0.48-0.95; P = .02). Additionally, the 6-month OS rate was 60.7% (95% CI, 50.3%-71.2%) vs 44.7% (95% CI, 34.2%-55.3%). Investigators also reported an overall response rate by MICR of 12.5% vs 3.5% (P = .04) in the irinotecan and fluorouracil/leucovorin arms, respectively.

Data from a prespecified subgroup analysis indicated that bone metastases and primary tumor locations demonstrated a significant interaction favoring the experimental cohort in patients diagnosed with gallbladder cancer and bone metastases in terms of PFS and OS. However, investigators note that these data should be interpreted with caution due to the small populations of each subgroup.

It is also worth noting that the single country included in the study and patients being of the same ethnicity may limit how generalizable these data are.

Reference

Hyung J, Kim I, Kim KP, et al. Treatment with liposomal irinotecan plus fluorouracil and leucovorin for patients with previously treated metastatic biliary tract cancer. JAMA Oncol. Published online March 23, 2023. doi:10.1001/jamaoncol.2023.0016