Efficacy and safety of weekly nab-paclitaxel (nab-P) plus gemcitabine (Gem) in Chinese patients (Pts) with metastatic adenocarcinoma of the pancreas (MPC): A phase II study

Aim/Background

Pancreatic cancer is the ninth most common cancer in China, with an estimated 88,500 new cases in 2012. In the global phase III MPACT trial (N = 861), nab-P + Gem demonstrated significantly better overall survival (OS; median: 8.7 vs 6.6 months; HR 0.72; P < 0.001) and overall response rate (ORR; 23% vs 7%; P < 0.001) than Gem alone as first-line treatment for pts with MPC. This phase II bridging study was designed to complement the MPACT trial by evaluating efficacy and safety of nab-P + Gem in Chinese pts with MPC.

Methods

This was a 3-part sequential study. Part 1 (dose evaluation) examined safety of nab-P 125 mg/m² + Gem 1000 mg/m² on days 1, 8, and 15 every 4 weeks (qw 3/4) in 10 pts. Part 2 (1-arm efficacy evaluation) examined efficacy by the Simon optimal 2-stage design. If there were > 2 responses in 28 pts in stage 1, an additional 54 pts would be evaluated in stage 2. The study would be completed if > 9 responses were observed. If after stage 1 or 2, an insufficient number of responses were observed, part 3 (randomized 2-arm design) would be triggered to compare nab-P + Gem vs Gem alone. The primary endpoint was ORR. Secondary endpoints included duration of response (DOR), OS, and safety.

Results

Eighty-three pts were enrolled. Median age was 57.0 years; 19% were aged > 65 years; 70% had a baseline Karnofsky performance status (KPS) of 90 - 100, and 30% had a KPS of 70 - 80. All pts received nab-P 125 mg/m² + Gem 1000 mg/m² qw 3/4. Combining results for stages 1 and 2, 29 pts had an objective response (ORR = 35%) by independent assessment, median DOR was 8.9 months (95% CI, 6.01 - 8.94), and median OS was 9.2 months (95% CI, 7.6 - 11.10). The most common grade ≥ 3 adverse events were neutropenia (37%), leukopenia (31%), fatigue (14%), and thrombocytopenia (13%). Grade ≥ 3 peripheral neuropathy occurred in 7% of pts. The ORR endpoint for part 2 was met, so the study did not progress to part 3.

Conclusions

nab-P + Gem demonstrated promising efficacy in Chinese pts with MPC. The OS and ORR were slightly better than those of the phase III MPACT trial. No new safety signals were identified.

Clinical trial identification

NCT02135822

Disclosure

M. Li, D. Begic, B. Lu: Celgene employee and stock owner. All other authors have declared no conflicts of interest.