(18)F-FDG PET/CT response in a phase 1/2 trial of nab-paclitaxel plus gemcitabine for advanced pancreatic cancer

BACKGROUND: Positron emission tomography (PET) is poised to become a useful imaging modality in staging and evaluating therapeutic responses in patients with metastatic pancreatic cancer (mPC). This analysis from a phase 1/2 study examined the utility of early PET imaging in patients with mPC treated with nab-paclitaxel plus gemcitabine. METHODS: Tumors were measured by [(18)F]2-fluoro-2-deoxyglucose PET/computed tomography (CT) in patients who received nab-paclitaxel 100 (n = 13), 125 (n = 38), or 150 (n = 1) mg/m(2) plus gemcitabine 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle. Lesion metabolic activity was evaluated at baseline and 6 and 12 weeks postbaseline. RESULTS: Fifty-two patients had baseline and ≥1 follow-up PET scan. The median maximum standardized uptake values per pancreatic lesion in the nab-paclitaxel 100 mg/m(2) and 125 mg/m(2) cohorts were 5.1 and 6.5, respectively. Among patients who had a metabolic response by PET, those who received nab-paclitaxel 125 mg/m(2) had a 4-month survival advantage over those who received 100 mg/m(2). All patients in the nab-paclitaxel 125 mg/m(2) cohort experienced an early complete metabolic response (CMR; 34%) or partial metabolic response (PMR; 66%). In the nab-paclitaxel 125 mg/m(2) cohort, investigator-assessed objective response rates were 77% and 44% among patients with a CMR and PMR, respectively, with no correlation between PET and CT response (Spearman r (s) = 0.22; P = 0.193). Patients in the nab-paclitaxel 125 mg/m(2) cohort with a CMR experienced a significantly longer overall survival vs those with a PMR (median, 23.0 vs 11.2 months; P = 0.011), and a significant correlation was found between best percentage change in tumor burden by PET and survival: for each 1% decrease in PET score, the risk of death decreased by 2%. CONCLUSIONS: The majority of primary pancreatic tumors and their metastases were PET avid, and PET effectively measured changes in tumor metabolic activity at 6 and 12 weeks. These results support the antitumor activity of nab-paclitaxel 125 mg/m(2) plus gemcitabine 1000 mg/m(2) for treating mPC and the utility of PET for measuring treatment response. Treatment response by PET analysis may be considered when evaluating investigational agents in mPC. TRIAL REGISTRATION: NCT00398086.