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Liposomal Irinotecan Combo Boosts Survival in Biliary Tract Cancer

Adding liposomal irinotecan to fluorouracil and leucovorin significantly improved progression-free survival (PFS) in patients with advanced biliary tract cancer after progression on gemcitabine plus cisplatin, according to results from a randomized phase IIb trial.

At a median follow-up of 11.8 months, the liposomal irinotecan combination resulted in a blinded independent central review (BICR)-assessed PFS of 7.1 months compared with 1.4 months with fluorouracil and leucovorin alone, translating into a 44% reduced risk of progression (HR 0.56, 95% CI 0.39-0.81, P=0.0019), reported Changhoon Yoo, MD, of Asan Medical Center at the University of Ulsan College of Medicine in Seoul, South Korea, and colleagues.

In addition, overall survival (OS) was 8.6 months with liposomal irinotecan versus 5.5 months without (HR 0.68, 95% CI 0.48-0.98, P=0.035).

Based on the trial’s findings, “liposomal irinotecan plus fluorouracil and leucovorin could be considered as one of the standard-of-care second-line chemotherapy regimens for advanced biliary tract cancer,” Yoo and colleagues wrote in Lancet Oncology.

The investigators also observed that the BICR-assessed 6-month PFS rate was 55.7% in the liposomal irinotecan group compared with 26.2% in the group that received fluorouracil and leucovorin alone, while the 6-month OS rates were 60.8% versus 45.9%. The BICR-assessed objective response rate was 14.8% versus 5.8%, respectively, while the disease control rates were 64.8% and 34.9%, respectively.

Liposomal irinotecan is an intravenous liposomal formulation of irinotecan, a DNA topoisomerase I inhibitor, which was approved for the treatment of patients with gemcitabine-refractory metastatic pancreatic cancer based on results from the NAPOLI-1 trial. In that study, liposomal irinotecan plus fluorouracil and leucovorin extended survival in patients with metastatic pancreatic adenocarcinoma compared with fluorouracil and leucovorin alone.

Yoo and colleagues noted that biliary tract cancer has an enriched stroma like pancreatic cancer, and thus hypothesized that liposomal irinotecan would also be effective in this setting.

Their multicenter open-label study, known as NIFTY, was conducted at five academic institutions in South Korea and included 174 patients (median age 64, 57% men) with histologically or cytologically confirmed metastatic biliary tract cancer that had progressed on first-line gemcitabine plus cisplatin. Patients had an Eastern Cooperative Oncology Group performance status of 0 or 1.

The authors noted that there was a divergence between the values for BICR-assessed PFS and the investigator-assessed PFS of 3.9 months in the liposomal irinotecan group and 1.6 months in the fluorouracil and leucovorin alone group (HR 0.48, 95% CI 0.34-0.69, P<0.0001).

“Discrepancies between the values for BICR-assessed and investigator-assessed median progression-free survival were caused by discordance in the date of tumor progression between investigators and independent radiological reviewers,” they wrote. However, they pointed out that the HRs for median PFS were similar between the two.

The most common grade 3/4 adverse event reported in the liposomal irinotecan group was neutropenia, which occurred in 24% of patients compared with 1% in the fluorouracil and leucovorin group. Grade 3 fatigue or asthenia were reported in 13% and 3%, respectively.

Serious adverse events occurred in 42% of patients in the liposomal irinotecan group and 24% of those in the fluorouracil and leucovorin group. No treatment-related deaths were reported.

  • Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.

Disclosures

This study was funded in part by Servier and HK inno.N.

Yoo reported receiving honoraria from Servier, Bayer, AstraZeneca, Merck Sharp & Dohme, Eisai, Celgene, Bristol Myers Squibb, Debiopharm, Ipsen, Kyowa Kirin, Novartis, Boryung Pharmaceuticals, Merck Serono, Mundipharma, Roche, and Janssen, and receiving research grants from Servier, Bayer, AstraZeneca, Ono Pharmaceuticals, Celgene, Ipsen, Boryung Pharmaceuticals, and Ildong Pharmaceuticals.

Other co-authors reported multiple relationships with industry.

Beal reported no disclosures.

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Source: MedicalNewsToday.com