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

Ronald L Korn, Daniel D Von Hoff, Mitesh J Borad, Markus F Renschler, Desmond McGovern, R Curtis Bay, Ramesh K Ramanathan, Ronald L Korn, Daniel D Von Hoff, Mitesh J Borad, Markus F Renschler, Desmond McGovern, R Curtis Bay, Ramesh K Ramanathan

Abstract

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 [18F]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/m2 plus gemcitabine 1000 mg/m2 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/m2 and 125 mg/m2 cohorts were 5.1 and 6.5, respectively. Among patients who had a metabolic response by PET, those who received nab-paclitaxel 125 mg/m2 had a 4-month survival advantage over those who received 100 mg/m2. All patients in the nab-paclitaxel 125 mg/m2 cohort experienced an early complete metabolic response (CMR; 34%) or partial metabolic response (PMR; 66%). In the nab-paclitaxel 125 mg/m2 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/m2 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/m2 plus gemcitabine 1000 mg/m2 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.

Keywords: Gemcitabine; Pancreatic cancer; Phase 1/2 clinical trial; Positron emission tomography; nab-Paclitaxel.

Conflict of interest statement

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice, Guidelines of the International Conference on Harmonization. Written informed consent was obtained from all patients before entering the study.

Consent for publication

Not applicable.

Competing interests

RLK: research funding: Celgene; DDVH: consultant or advisory role, honoraria, and research funding: Celgene; MJB: nothing to disclose; RCB: consultant: Celgene; DM: employment: Celgene; MFR: employment: Celgene; RKR: consultant or advisory role, honoraria, and research funding: Celgene.

The manuscript has not been submitted for publication nor is it under consideration for publication elsewhere.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Waterfall plot of best responses by 18F-FDG PET/CT. CMR, complete metabolic response; CT, computed tomography; nab-P, nab-paclitaxel; PET, positron emission tomography; PMR, partial metabolic response; SMD, stable metabolic disease. a The blue circle represents 0% best response from a single patient in the nab-P 100 mg/m2 cohort
Fig. 2
Fig. 2
Overall survival by PET metabolic response among patients in the nab-paclitaxel 125 mg/m2 cohort. CMR, complete metabolic response; OS, overall survival; PET, positron emission tomography; PMR, partial metabolic response
Fig. 3
Fig. 3
Time to best response by CT in the 125 and 100 mg/m2nab-paclitaxel cohorts. CT, computed tomography

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