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).

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

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

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

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