Abstract
A recent analysis from the MPACT trial supported the use of carbohydrate antigen 19-9 (CA19-9) decrease as a predictive marker for survival in patients receiving nab-paclitaxel plus gemcitabine or gemcitabine alone for metastatic pancreatic cancer; however, CA19-9 cannot be used in this capacity for the 15% to 20% of patients who do not produce elevated levels at baseline, leaving fewer tools for predicting outcomes in these patients. Decreases in tumor metabolic activity as measured by positron emission tomography (PET) also predicted longer survival in the MPACT trial. Here we report that tumor metabolic response measured by PET significantly predicted longer survival in patients in the MPACT trial who did not produce elevated CA19-9 at baseline.
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, 2]. 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, 4]. 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]) 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 1.
Overall 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 cohort |
HR (P-value) | ||
|---|---|---|---|
| Yes PET MR | No PET MR | ||
| Week 8 | n = 21 | n = 17 | |
| Median OS, months | 13.2 | 8.0 | 0.34 (0.001) |
| (95% CI) | (9.20–17.05) | (3.38–14.69) | |
| One-year survival rate | 52% | 35% | |
| Best response during treatment | n = 24 | n = 16 | |
| Median OS, months | 13.6 | 6.9 | 0.31 (0.003) |
| (95% CI) | (9.26–22.83) | (3.38–10.22) | |
| One-year survival rate | 58% | 25% | |
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.
funding
This work was supported in part by a grant from Stand Up 2 Cancer and Celgene Corporation (no grant number).
disclosure
RKR: consultant or advisory role, honoraria, and research funding, Celgene Corporation; RK: research funding, Celgene Corporation; EGC: research funding, Celgene Corporation; HL: employment and stock ownership, Celgene Corporation; DDVH: consultant or advisory role, honoraria, and research funding, Celgene Corporation.
references
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