Nanoliposomal Irinotecan Effective for Pancreatic Cancer

Summary and Comment |
December 8, 2015

Nanoliposomal Irinotecan Effective for Pancreatic Cancer

  1. David H. Ilson, MD, PhD

Adding nanoliposomal irinotecan to 5-fluorouracil and folinic acid significantly improved overall survival in patients with gemcitabine-refractory disease.

  1. David H. Ilson, MD, PhD

Progress has been made in the treatment of patients with advanced pancreatic cancer, with combination chemotherapy modestly improving overall survival compared with single-agent gemcitabine. However, after FOLFIRINOX or gemcitabine-based first-line chemotherapy, there is no standard second-line chemotherapy.

Investigators now report results of the NAPOLI-1 trial, an industry-sponsored, global, open-label, randomized phase III study of nanoliposomal-encapsulated irinotecan in 417 patients with pancreatic cancer who experienced disease progression with gemcitabine-based chemotherapy. Patients were randomized to receive nanoliposomal irinotecan monotherapy; 5-fluorouracil (5-FU) plus folinic acid; or nanoliposomal irinotecan followed by folinic acid and 5-FU. Results were as follows:

  • Median overall survival (OS; the primary endpoint) was improved with nanoliposomal irinotecan, 5-FU, and folinic acid combination therapy versus 5-FU and folinic acid (6.1 vs. 4.2 months; hazard ratio, 0.67; P=0.012).

  • OS was similar with nanoliposomal irinotecan monotherapy or 5-FU and folinic acid (4.9 and 4.2 months, respectively).

  • Progression-free survival was superior with nanoliposomal irinotecan combination therapy versus 5-FU and folinic acid (3.1 vs. 1.5 months; HR, 0.56; P=0.0001).

  • Response rates were superior with nanoliposomal irinotecan combination therapy (16%) and nanoliposomal irinotecan monotherapy (6%) versus 5-FU and folinic acid (1%).

Grade 3 or 4 toxicities, including diarrhea, vomiting, fatigue, and neutropenia, were greater with nanoliposomal irinotecan combination therapy than with 5-FU and folinic acid. Patients homozygous for the UGT1A1*28 allele, a potential marker for greater irinotecan toxicity, received nanoliposomal irinotecan at a lower dose, but this accounted for only 5% to 6% of patients, and 30% to 40% of these tolerated a planned dose escalation of nanoliposomal irinotecan.

Comment

In patients with gemcitabine-refractory pancreatic cancer, the combination of nanoliposomal irinotecan plus infusional 5-FU and folinic acid improved survival versus 5-FU and folinic acid. This combination represents a new care standard in this setting. Whether this novel irinotecan formulation offers any advantage over conventional irinotecan, however, is unclear. Also, this therapy likely has no role after disease progression on FOLFIRINOX, which contains infusional 5-FU and irinotecan.

Editor Disclosures at Time of Publication

  • Disclosures for David H. Ilson, MD, PhD at time of publication Consultant / Advisory board Amgen; Eli Lilly–ImClone; Macrogenics; Bayer Speaker’s bureau Genentech/Roche Grant / Research support Bayer; Amgen; Bristol-Myers Squibb

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