nal-IRI+5-FU/LV versus 5-FU/LV in post-gemcitabine metastatic pancreatic cancer: Randomized phase 2 trial in Japanese patients.

Abstract

BACKGROUND:

In the NAPOLI-1 phase 3 trial, liposomal irinotecan (nal-IRI) +5-fluorouracil/leucovorin (5-FU/LV) significantly increased mPFS versus 5-FU/LV (3.1 vs. 1.5 months [unstratified HR = 0.56, p = 0.0001]) in patients with mPAC that progressed on prior gemcitabine-based therapy. This randomized phase 2 trial evaluated nal-IRI+5-FU/LV tolerability (Part 1), safety, and efficacy (Part 2; outcomes reported here) in Japanese patients with mPAC that progressed on gemcitabine-based therapy.

METHODS:

Patients were randomized 1:1 and stratified by KPS (70 and 80 vs. ≥90) and baseline albumin (≥4.0 g/dl vs. <4.0 g/dl). Primary endpoint was PFS; secondary endpoints were ORR, DCR, OS, TTF, CA19-9 response, and QoL. The ITT population comprised all randomized patients.

RESULTS:

Patient characteristics differed between nal-IRI+5-FU/LV (n = 40) and 5-FU/LV (n = 39) arms, including baseline hepatic lesions (63% vs. 51%), stage IV disease at diagnosis (78% vs. 51%), and post-study anticancer therapy (55% vs. 72%). Investigator-assessed mPFS increase with nal-IRI+5-FU/LV was clinically meaningful and statistically significant versus 5-FU/LV (2.7 vs. 1.5 months, HR = 0.60). Independently assessed mPFS showed similar trends (1.7 vs. 1.6 months, HR = 0.79). mOS was 6.3 months with nal-IRI+5-FU/LV and not reached with 5-FU/LV. ORR increased significantly with nal-IRI+5-FU/LV versus 5-FU/LV (18% vs. 0, rate difference 17.5). Commonly reported grade ≥3 treatment-emergent AEs were decreased neutrophil count (37% vs. 3%), decreased white blood cell count (20% vs. 0), and diarrhea (17% vs. 3%).

CONCLUSIONS:

In conclusion, clinically meaningful and statistically significant gains in investigator-assessed PFS and ORR were observed with nal-IRI+5-FU/LV versus 5-FU/LV in Japanese patients, with no new or unexpected safety signals. (Clinicaltrials.gov ID: NCT02697058).

• Authors: Makoto Ueno, Shoji Nakamori, Kazuya Sugimori, Masashi Kanai, Masafumi Ikeda, Masato Ozaka, Masayuki Furukawa, Takuji Okusaka, Ken Kawabe, Junji Furuse, Yoshito Komatsu, Hiroshi Ishii, Atsushi Sato, Satoshi Shimizu, Priti Chugh, Rui Tang, Tatsuya Ioka
• Journal: Cancer medicine (Cancer Med) Vol. 9 Issue 24 Pg. 9396-9408 (12 2020) ISSN: 2045-7634 [Electronic] United States
• PMID: 33099898 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Liposomes
• Deoxycytidine
• Irinotecan
• Leucovorin
• Fluorouracil
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Drug Resistance, Neoplasm
• Female
• Fluorouracil (administration & dosage)
• Humans
• Irinotecan (administration & dosage)
• Japan
• Leucovorin (administration & dosage)
• Liposomes (administration & dosage)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Pancreatic Neoplasms (drug therapy, pathology)
• Survival Rate
• Gemcitabine