Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study
Abstract
1. Introduction
2. Patients and Methods
2.1. Treatment Protocol
2.2. Laboratory and Imaging Studies
2.3. Pathology
2.4. Statistical Analysis
3. Results
3.1. Patient Characteristics
3.2. Chromogranin A Data
3.3. Treatment Cycles
3.4. Response Assessment
3.5. Survival Analysis
3.6. Safety Profile
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Parameter | Total |
---|---|
(N = 25) | |
Median (min,max) | |
Age (in years) ^ | 56.9 (37.6,79.9) |
Tumor size (in mm) * | 35.0 (15.0,100.0) |
Ki67 (% of positive nuclei per 2000 cells, central assessment) * | 0.0 (0.0–20.0) |
N (%) | |
Sex | |
Man | 10 (40.0) |
Woman | 15 (60.0) |
PS | |
0 | 19 (76.0) |
1 | 6 (24.0) |
Sporadic | |
No | 4 (16.0) |
Yes | 21 (84.0) |
MEN testing | |
No | 24 (96.0) |
Yes | 1 (4.0) |
Initial surgery | |
No | 12 (48.0) |
Yes | 13 (52.0) |
Type of surgery | |
Laparotomy | 1 (7.7) |
Open surgery | 12 (92.3) |
Type of open surgery | |
Total resection | 4 (33.3) |
Subtotal resection | 5 (41.7) |
Other ** | 3 (25.0) |
Tumor localization | |
Jejunum | 2 (8.0) |
Ileus | 4 (16.0) |
Colon | 2 (8.0) |
Pancreas | 10 (40.0) |
Unknown primary | 2 (8.0) |
Other *** | 5 (20.0) |
Tumor grade | |
G1 [Low grade] | 11 (44.0) |
G2 [Intermediate grade] | 14 (56.0) |
Ki67 (local assessment) | |
<3% | 11(44.0) |
3–20% | 14 (56.0) |
Ki67 (central assessment) * | |
<3% | 10 (58.8) |
3–20% | 7 (41.2) |
Locally advanced ^ | |
No | 21 (84.0) |
Yes | 4 (16.0) |
Number of metastatic sites ^ | |
0 | 4 (16.0) |
1 | 17 (68.0) |
2 | 4 (16.0) |
Site of metastases ^ | |
Lung | 0 (0.0) |
Liver | 19 (76.0) |
Bones | 0 (0.0) |
LNS | 5 (20.0) |
Other **** | 1 (4.0) |
CgA | Time point | ||
---|---|---|---|
Baseline | Last Cycle | p-Value | |
N | 24 | 12 | >0.999 ^ |
mean (std) | 21.22 (30.36) | 16.05 (25.73) | |
median | 3.50 | 4 | |
min-max | 1.57–102.0 | 2.30–91.60 | |
p25–p75 | 2.55–27.60 | 2.90-21.50 | |
Normal (N,%) | 13 (54.2) | 5 (41.7) | 0.16 ^^ |
Abnormal (N,%) | 11 (45.8) | 7 (58.3) |
Adverse Event | Grade 1 | Grade 2 | ||||
---|---|---|---|---|---|---|
System Organ Class | N of evts | N of pts | % pts | N of evts | N of pts | % pts |
Preferred Term | ||||||
Anemia | 5 | 5 | 20.00 | 3 | 3 | 12.00 |
Diarrhea | 2 | 2 | 8.00 | 6 | 6 | 24.00 |
Edema limbs | 4 | 4 | 16.00 | 1 | 1 | 4.00 |
Fatigue | 4 | 4 | 16.00 | 2 | 2 | 8.00 |
Fever | 4 | 4 | 16.00 | 1 | 1 | 4.00 |
Alanine aminotransferase increased | 6 | 6 | 24.00 | 4 | 4 | 16.00 |
Alkaline phosphatase increased | 7 | 7 | 28.00 | 0 | 0 | 0.00 |
Aspartate aminotransferase increased | 6 | 6 | 24.00 | 4 | 4 | 16.00 |
Cholesterol high | 6 | 6 | 24.00 | 2 | 2 | 8.00 |
Creatinine increased | 3 | 3 | 12.00 | 1 | 1 | 4.00 |
GGT increased | 2 | 2 | 8.00 | 5 | 5 | 20.00 |
White blood cell decreased | 4 | 4 | 16.00 | 1 | 1 | 4.00 |
Hyperglycemia | 8 | 8 | 32.00 | 8 | 8 | 32.00 |
Hypertriglyceridemia | 5 | 5 | 20.00 | 1 | 1 | 4.00 |
Hypocalcemia | 4 | 4 | 16.00 | 1 | 1 | 4.00 |
Hypokalemia | 3 | 3 | 12.00 | 1 | 1 | 4.00 |
Hypophosphatemia | 2 | 2 | 8.00 | 3 | 3 | 12.00 |
Rash maculo-papular | 4 | 4 | 16.00 | 2 | 2 | 8.00 |
Adverse Event | Grade 3 | Grade 4 | ||||
---|---|---|---|---|---|---|
System Organ Class | N of evts | N of pts | % pts | N of evts | N of pts | % pts |
Preferred Term | ||||||
Total | 16 | 11 | 44.00 | 2 | 2 | 8.00 |
Blood and lymphatic system disorders | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Anemia | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Gastrointestinal disorders | 5 | 5 | 20.00 | 0 | 0 | 0.00 |
Diarrhea | 2 | 2 | 8.00 | 0 | 0 | 0.00 |
Mucositis oral | 3 | 3 | 12.00 | 0 | 0 | 0.00 |
Infections and infestations | 2 | 2 | 8.00 | 0 | 0 | 0.00 |
Infections and infestations - Other, specify * | 2 | 2 | 8.00 | 0 | 0 | 0.00 |
Investigations | 4 | 4 | 16.00 | 2 | 2 | 8.00 |
Alanine aminotransferase increased | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
CPK increased | 1 | 1 | 4.00 | 1 | 1 | 4.00 |
GGT increased | 1 | 1 | 4.00 | 1 | 1 | 4.00 |
Neutrophil count decreased | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Metabolism and nutrition disorders | 3 | 3 | 12.00 | 0 | 0 | 0.00 |
Anorexia | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Hyperglycemia | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Hypokalemia | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Vascular disorders | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
Hypertension | 1 | 1 | 4.00 | 0 | 0 | 0.00 |
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Koumarianou, A.; Pectasides, D.; Koliou, G.-A.; Dionysopoulos, D.; Kolomodi, D.; Poulios, C.; Skondra, M.; Sgouros, J.; Pentheroudakis, G.; Kaltsas, G.; et al. Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study. Biology 2020, 9, 51. https://doi.org/10.3390/biology9030051
Koumarianou A, Pectasides D, Koliou G-A, Dionysopoulos D, Kolomodi D, Poulios C, Skondra M, Sgouros J, Pentheroudakis G, Kaltsas G, et al. Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study. Biology. 2020; 9(3):51. https://doi.org/10.3390/biology9030051
Chicago/Turabian StyleKoumarianou, Anna, Dimitrios Pectasides, Georgia-Angeliki Koliou, Dimitrios Dionysopoulos, Dionysia Kolomodi, Christos Poulios, Maria Skondra, Joseph Sgouros, George Pentheroudakis, Gregory Kaltsas, and et al. 2020. "Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study" Biology 9, no. 3: 51. https://doi.org/10.3390/biology9030051
APA StyleKoumarianou, A., Pectasides, D., Koliou, G.-A., Dionysopoulos, D., Kolomodi, D., Poulios, C., Skondra, M., Sgouros, J., Pentheroudakis, G., Kaltsas, G., & Fountzilas, G. (2020). Efficacy and Safety of First-Line Everolimus Therapy Alone or in Combination with Octreotide in Gastroenteropancreatic Neuroendocrine Tumors. A Hellenic Cooperative Oncology Group (HeCOG) Study. Biology, 9(3), 51. https://doi.org/10.3390/biology9030051