Article Figures & Data
Figures
- Figure 1.
Treatment schema. Gemcitabine (1,000 mg/m2) was infused on days 1, 8, and 15 of each 28-day cycle, with CP-870,893 administered once during each treatment cycle on day 3.
- Figure 2.
FDG-PET/CT imaging of (A and B) primary pancreatic tumors and (C and D) metastatic hepatic lesions. A and C, change relative to baseline in MVPmean as a measure of metabolic activity. B and D, CT, FDG-PET, and fused PET/CT images (baseline vs. end of cycle 4) showing (B), a responding primary pancreatic lesion (green arrow) and (D) a mixed response in liver with representative new or progressive lesions (red arrowheads), stable lesions (yellow arrowheads), and responding lesions (green arrows). Normal FDG excretion in kidneys and ureters is also seen.
- Figure 3.
The response of individual lesions measured by changes in lesional MVPmean from baseline to end of cycle 2, shown for: A, each patient, and B, for each metastatic site (all patient lesions pooled) including liver, lung, lymph node (LN), and peritoneal cavity. Changes in MVPmean were classified as CMR indicating disappearance of lesion; PMR indicating ≥25% reduction in MVPmean; progressive metabolic disease (PMD) indicating >25% increase in MVPmean or new lesion; and stable metabolic disease (SMD) indicating insufficient decrease to qualify for PMR and insufficient increase to qualify for PMD.
- Figure 4.
Biologic correlatives for OS after treatment with CP-870,893 in combination with gemcitabine. A, median OS and PFS for patients (n = 21) receiving at least one dose of CP-870,893. Relationship between (B) percentage change in CA19-9 at end of one cycle of therapy compared with baseline (R = −0.579; P = 0.049), (C) OS and tumor response determined by RECIST 1.0 at completion of two cycles of therapy (R = −0.652; P = 0.002), and (D) percentage change in total MVPmean for all lesions, primary pancreatic lesion, and all hepatic lesions after 2 weeks of therapy compared with baseline (R = −0.929; P = 0.007). Best overall tumor response measured by RECIST 1.0 is indicated in (B), (C), and (D) using open circles (PR), gray circles (stable disease), and black circles (progressive disease).
Tables
- Table 1.
Baseline patient demographics and clinical characteristics
CP-870,893 Dose cohort 0.1 mg/kg (n = 3) 0.2 mg/kg (n = 6) MTD expansion 0.2 mg/kg (n = 13) Characteristic n (%) n (%) n (%) Age, y Median 59 59 Range 57–72 40–81 Sex Male 2 (67) 3 (50) 9 (69) Female 1 (33) 3 (50) 4 (31) Race/ethnicity White 0 (0) 5 (83) 11 (84) Black 3 (100) 1 (17) 1 (8) Asian 0 (0) 0 (0) 1 (8) ECOG PS 0 2 (67) 5 (83) 2 (15) 1 1 (33) 1 (17) 11 (85) Extent of disease Locally advanced 0 (0) 0 (0) 2 (15) Metastatic 3 (100) 6 (100) 11 (85) Location of primary Head 2 (67) 2 (33) 4 (31) Body or tail 1 (33) 2 (33) 9 (69) Not reported 0 (0) 2 (33) 0 (0) Site of metastases Liver 3 (100) 5 (83) 10 (77) Lung 0 (0) 2 (33) 0 (0) Peritoneal 0 (0) 0 (0) 3 (23) Skeleton 0 (0) 2 (33) 0 (0) Other 0 (0) 0 (0) 1 (8) Prior radiotherapies No 3 (100) 6 (100) 11 (84) Yes 0 (0) 0 (0) 1 (8) Not reported 0 (0) 0 (0) 1 (8) - Table 2.
Summary of the most commonly reported adverse events by grade
CP-870,893 dose cohort 0.1 mg/kg (n = 3) 0.2 mg/kg (n = 6) MTD expansion 0.2 mg/kg (n = 13) Grade 1 or 2 Grade 3 or 4 Grade 1 or 2 Grade 3 or 4 Grade 1 or 2 Grade 3 or 4 Adverse events n (%) n (%) n (%) n (%) n (%) n (%) Clinical events CRS 2 (67) 1 (33) 6 (100) 0 (0) 11 (85) 0 (0) Fatigue 3 (100) 0 (0) 5 (83) 0 (0) 11 (85) 0 (0) Nausea 3 (100) 0 (0) 5 (83) 0 (0) 10 (77) 0 (0) Vomiting 1 (33) 0 (0) 3 (50) 0 (0) 6 (46) 0 (0) Pyrexia 1 (33) 0 (0) 1 (17) 0 (0) 6 (46) 0 (0) Peripheral edema 3 (100) 0 (0) 2 (33) 0 (0) 3 (23) 0 (0) Constipation 1 (33) 0 (0) 3 (50) 0 (0) 6 (46) 0 (0) Cerebrovascular accident 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (8) Hematologic events Anemia 3 (100) 0 (0) 4 (67) 1 (17) 10 (77) 2 (15) Lymphopenia 1 (33) 1 (33) 4 (67) 0 (0) 7 (54) 4 (31) Neutropenia 2 (67) 0 (0) 1 (17) 3 (50) 3 (23) 2 (15) Thrombocytopenia 2 (67) 0 (0) 3 (50) 0 (0) 3 (23) 0 (0) Nonhematologic events ALT 2 (67) 0 (0) 4 (67) 0 (0) 8 (62) 0 (0) AST 2 (67) 0 (0) 3 (50) 0 (0) 11 (85) 0 (0) Alkaline Phosphatase 2 (67) 0 (0) 5 (83) 1 (17) 8 (62) 2 (15) Total bilirubin 2 (67) 1 (33) 2 (33) 1 (17) 5 (38) 1 (8) Hyperglycemia 2 (67) 1 (33) 2 (33) 4 (67) 11 (85) 1 (8) Hypocalcemia 2 (67) 0 (0) 1 (17) 0 (0) 10 (77) 0 (0) Hyponatremia 2 (67) 0 (0) 3 (50) 0 (0) 2 (15) 2 (15)
Supplementary Data
Files in this Data Supplement:
- Supplementary Figure Legends - Supplementary Figure Legends - PDF file 64K, Supplementary Figure Legends
- Supplementary Figure 1 - Supplementary Figure 1 - PDF file 99K, Pharmacodynamic effects of gemcitabine and CP-870,893
- Supplementary Figure 2 - Supplementary Figure 2 - PDF file 71K, Analysis of cytokines as correlatives of overall survival
- Supplementary Table 1 - Supplementary Table 1 - PDF file 56K, Spearman Rank Correlation Analysis of Biomarkers for Overall Survival
CCR Translation for This Article
The following CCR Translation is available for this article:
Harnessing Immune Responses in the Tumor Microenvironment: All Signals Needed
Dung T. Le and Elizabeth M. Jaffee
Volume 19, Issue 22
