Positron emission tomography (PET) as a predictive measure in patients with metastatic pancreatic cancer and normal CA19-9 levels at baseline
Authors: R.K. Ramanathan, R.L. Korn, E.G. Chiorean, H. Liu, D.D. Von Hoff
Journal: Annals of Oncology (2016)

Two recent MPACT subanalyses (Chiorean et al. and Ramanathan et al. Ann Oncol. 2016) demonstrated evidence that decreases from baseline in carbohydrate antigen 19-9 (CA19-9) and tumor uptake of radioactively labeled glucose (18F-FDG) as measured by positron emission tomography (PET) imaging were each significantly associated with longer overall survival (OS) in patients who received first-line treatment with nab-paclitaxel plus gemcitabine or gemcitabine for metastatic pancreatic cancer [1.Chiorean E.G. Von Hoff D.D. Reni M. et al.CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine vs gemcitabine alone in patients with metastatic pancreatic cancer.Ann Oncol. 2016; 27: 654-660Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar, 2.Ramanathan R.K. Goldstein D. Korn R.L. et al.Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas.Ann Oncol. 2016; 27: 648-653Abstract Full Text Full Text PDF PubMed Scopus (35) Google Scholar]. These modalities are complementary approaches to monitor treatment efficacy in most patients. However, we raised the question of whether tumor response measured by PET could predict outcome for a subset of patients (15%–20%) with pancreatic cancer who do not secrete elevated levels of CA19-9 [3.Bauer T.M. El-Rayes B.F. Li X. et al.Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials.Cancer. 2013; 119: 285-292Crossref PubMed Scopus (91) Google Scholar, 4.Tempero M.A. Uchida E. Takasaki H. et al.Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer.Cancer Res. 1987; 47: 5501-5503PubMed Google Scholar]. In the MPACT trial, more patients experienced a metabolic response (MR) measured by PET imaging than a tumor response measured by computed tomography. PET imaging may be particularly valuable to predict outcomes in patients without elevated baseline CA19-9 levels. We carried out a post hoc, pooled treatment-arm analysis of OS by PET response in patients without elevated CA19-9 levels at baseline (defined as <37 U/ml). Results for OS by MR (defined by European Organization for the Research and Treatment of Cancer [EORTC] criteria [5.Young H. Baum R. Cremerius U. et al.Measurement of clinical and subclinical tumour response using [18F]-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group.Eur J Cancer. 1999; 35: 1773-1782Abstract Full Text Full Text PDF PubMed Scopus (1454) Google Scholar]) are summarized in Table 1. MRs at week 8 and at best response during the study were each significantly associated with longer OS in patients with no CA19-9 elevation at baseline. Specifically, the median OS in patients with an MR at week 8 was 5.2 months longer than that in patients without one. In addition, patients with an MR at any time during the study had a nearly twofold longer median OS than those without one.Table 1Overall survival by metabolic response in patients without elevated baseline CA19-9 levels treated with nab-paclitaxel plus gemcitabine or gemcitabine alone (pooled)Patients without elevated CA19-9 levels at baseline in the PET cohortHR (P-value)Yes PET MRNo PET MRWeek 8n = 21n = 17Median OS, months13.28.00.34 (0.001)(95% CI)(9.20–17.05)(3.38–14.69)One-year survival rate52%35%Best response during treatmentn = 24n = 16Median OS, months13.66.90.31 (0.003)(95% CI)(9.26–22.83)(3.38–10.22)One-year survival rate58%25%CA19-9, carbohydrate antigen 19-9; MR, metabolic response; OS, overall survival; PET, positron emission tomography. Open table in a new tab CA19-9, carbohydrate antigen 19-9; MR, metabolic response; OS, overall survival; PET, positron emission tomography. These results illustrate that PET imaging may serve as a valuable tool to monitor treatment response in the subset of patients without elevated CA19-9 levels at baseline. Future trials may examine this issue more systematically as a preplanned end point. This work was supported in part by a grant from Stand Up 2 Cancer and Celgene Corporation (no grant number).