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

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, 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

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).

Keywords: chemotherapy; clinical trials; medical oncology; pancreatic cancer; pancreatic ductal adenocarcinoma.

© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram for patient disposition in study Part 2 (ITT population). *Not including patients receiving nal‐IRI+5‐FU/LV (n = 6) during study Part 1. The ITT population included all Part 2 patients even if they did not receive any study treatment. **One patient was randomized but not dosed as the patient was found to be in conflict with exclusion criteria prior to receiving study drug. 5‐FU, 5‐fluorouracil; ITT, intention‐to‐treat; LV, leucovorin; nal‐IRI, liposomal irinotecan
FIGURE 2
FIGURE 2
Progression‐free survival in study Part 2 (ITT population). Kaplan–Meier plots for PFS based on investigator assessment (A) and independent assessment (B) in the Part 2 ITT population. Tick marks indicate censoring points. 5‐FU, 5‐fluorouracil; CI, confidence interval; HR, hazard ratio; ITT, intention‐to‐treat; LV, leucovorin; nal‐IRI, liposomal irinotecan; PFS, progression‐free survival
FIGURE 3
FIGURE 3
Change from baseline in CA19‐9 tumor marker response in study Part 2 (TMRE population). 5‐FU, 5‐fluorouracil; CA19‐9, carbohydrate antigen 19‐9; LV, leucovorin; nal‐IRI, liposomal irinotecan; TMRE, tumor marker response evaluable

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Source: PubMed

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