Tumor Reduction in Primary and Metastatic Pancreatic Cancer Lesions With nab-Paclitaxel and Gemcitabine: An Exploratory Analysis From a Phase 3 Study

Abstract

Objectives: Results from the phase 3 Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) led to approval of nab-paclitaxel plus gemcitabine for first-line treatment of metastatic pancreatic cancer. The current analysis evaluated the effects of nab-paclitaxel plus gemcitabine versus gemcitabine on primary pancreatic and metastatic lesions.

Methods: In this analysis of the previously described MPACT trial, changes in pancreatic and metastatic tumor burden were assessed using independently measured diameters of lesions on computed tomography or magnetic resonance imaging scans. Changes in the sums of longest tumor diameters were summarized using descriptive statistics and were included in a multivariate analysis of overall survival.

Results: Primary pancreatic lesion measurement was feasible. Reductions in primary pancreatic tumor burden and metastatic burden from baseline to nadir were significantly greater with nab-paclitaxel plus gemcitabine versus gemcitabine. Baseline pancreatic tumor burden was independently predictive of survival. Both regimens elicited linear reductions in primary pancreatic and metastatic tumor burden through time. There was a high within-patient concordance of tumor changes between primary pancreatic lesions and metastatic lesions.

Conclusions: This analysis of MPACT demonstrated significant tumor shrinkage benefit for nab-paclitaxel plus gemcitabine in both primary pancreatic and metastatic lesions, supporting ongoing evaluation of this regimen in locally advanced disease.

FIGURE 1

Percentage change in tumor burden from baseline to nadir. The percent change in the sum of the longest diameters of the primary pancreatic (A) or metastatic (B) target lesions was calculated from baseline to nadir in the evaluable population for the gemcitabine monotherapy and nab-paclitaxel plus gemcitabine groups.

FIGURE 2

Percentage change in pancreatic target lesion sum of the longest diameters from baseline. The mean percent change in the sum of the longest diameters of the primary pancreatic target lesions in the evaluable population was calculated (±95% CI) from baseline to weeks 8, 16, and 24 for the gemcitabine monotherapy and nab-paclitaxel plus gemcitabine groups.

FIGURE 3

Percentage change in sum of the longest diameters of metastatic target lesions from baseline. The mean percent change in the sum of the longest diameters of the metastatic pancreatic tumors in the evaluable population was calculated (±95% CI) from baseline to weeks 8, 16, and 24 for the gemcitabine monotherapy and nab-paclitaxel plus gemcitabine groups.

FIGURE 4

Within-patient correlation between percentage change in pancreatic target lesion burden and metastatic target lesion burden. Distribution of percent change in metastatic burden from baseline versus percent change in pancreatic tumor burden from baseline is shown at weeks 8, 16, and 24 of treatment for each patient in the combination arm (open red circles) and each patient in the gemcitabine-alone arm (blue crosses). Linear fits were performed for data points in the combination group (solid red line) and gemcitabine-alone group (solid blue line). Gem, gemcitabine; nab-P, nab-paclitaxel.