TY - JOUR
T1 - Somatostatin Analogs for Pancreatic Neuroendocrine Tumors
T2 - Any Benefit When KI-67 is ≥10%?
AU - Merola, E
AU - Alonso Gordoa, T
AU - Zhang, P
AU - Al-Toubah, T
AU - Pelle, E
AU - Kolasińska-Ćwikła, A
AU - Zandee, W T
AU - Laskaratos, F M
AU - de Mestier, L
AU - Lamarca, A
AU - Hernando, J
AU - Cwikla, J B
AU - Strosberg, J
AU - de Herder, W W
AU - Caplin, M
AU - Cives, M
AU - van Leeuwaarde, R S
N1 - Funding Information:
The authors thank NET CONNECT for having made this study possible through logistical and organizational support provided by COR2ED. NET CONNECT is supported by an Independent Educational Grant from IPSEN. The program is therefore independent, and the content is not influenced by IPSEN and is under the sole responsibility of the experts. Elettra Merola, Teresa Alonso Gordoa, Panpan Zhang, Wouter Zandee, Faidon Laskaratos, Louis de Mestier, Angela Lamarca, Jorge Hernando, Wouter de Herder, Martin Caplin, Mauro Cives, and Rachel van Leeuwaarde are members of the NET CONNECT group. This research did not receive any specific grant from any funding agency in the public, commercial, or not‐for‐profit sector.
Funding Information:
ENETS excellence Academy fellowship 2017 (RF‐Grant awarded for another research project regarding neuroendocrine tumors); Ipsen, Novartis, Pfizer (C/A), Novartis (RF); Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan, Delcath (Other‐travel, educational support), Merck, Pfizer, Ipsen, Incyte, AAA (H‐Speaker), EISAI, Nutricia Ipsen, QED, Roche (H‐Advisory), Knowledge Network and NETConnect Initiatives funded by Ipsen (Other‐Member); Novartis (C/A), Ipsen, Lexicon (H); Ipsen (RF), AAA/Novartis (SAB); Novartis, AAA, Ipsen, Pfizer (H, SAB); AAA, Ipsen (SAB). The other authors indicate no financial relationships. Elettra Merola: Louis de Mestier: Angela Lamarca: Jonathan Strosberg: Wouter de Herder: Martin Caplin: Mauro Cives:
Publisher Copyright:
© 2020 AlphaMed Press
PY - 2021/4
Y1 - 2021/4
N2 - Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. Materials and Methods: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014–2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. Results: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6–173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6–16.2) and 11.9 months (95% CI, 8.6–14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2–16.6; p =.04) and hepatic tumor load (HR, 2; 95% CI, 1–4; p =.03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8–86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2–10; p =.01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. Conclusion: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. Implications for Practice: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
AB - Background: Long-acting somatostatin analogs (SSAs) are the primary first-line treatment of well-differentiated advanced gastroenteropancreatic neuroendocrine tumors (NETs), but data about their efficacy in pancreatic NETs (panNETs) with Ki-67 ≥10% are still limited. Materials and Methods: To assess the clinical outcomes of advanced, nonfunctioning, well-differentiated panNETs with Ki-67 ≥10% receiving first-line long-acting SSAs in a real-world setting, we carried out a retrospective, multicenter study including patients treated between 2014–2018 across 10 centers of the NET CONNECT Network. The primary endpoints were time to next treatment (TNT) and progression-free survival (PFS), whereas overall survival (OS) and treatment safety were secondary endpoints. Results: A total of 73 patients were included (68 grade [G]2, 5 G3), with liver metastases in 61 cases (84%). After a median follow-up of 36.4 months (range, 6–173), the median TNT and PFS were 14.2 months (95% confidence interval [CI], 11.6–16.2) and 11.9 months (95% CI, 8.6–14.1) respectively. No statistically significant difference was observed according to the somatostatin analog used (octreotide vs. lanreotide), whereas increased tumor grade (hazard ratio [HR], 4.4; 95% CI, 1.2–16.6; p =.04) and hepatic tumor load (HR, 2; 95% CI, 1–4; p =.03) were independently associated with shortened PFS. The median OS recorded was 86 months (95% CI, 56.8–86 months), with poor outcomes observed when the hepatic tumor burden was >25% (HR, 3.4; 95% CI, 1.2–10; p =.01). Treatment-related adverse events were reported in 14 patients, most frequently diarrhea. Conclusion: SSAs exert antiproliferative activity in panNETs with Ki-67 ≥10%, particularly in G2 tumors, as well as when hepatic tumor load is ≤25%. Implications for Practice: The results of the study call into question the antiproliferative activity of somatostatin analogs (SSAs) in pancreatic neuroendocrine tumors with Ki-67 ≥10%. Patients with grade 2 tumors and with hepatic tumor load ≤25% appear to derive higher benefit from SSAs. Prospective studies are needed to validate these results to optimize tailored therapeutic strategies for this specific patient population.
KW - G2
KW - G3
KW - Hepatic tumor load
KW - Lanreotide
KW - Octreotide
KW - Pancreatic neuroendocrine tumor
UR - http://www.scopus.com/inward/record.url?scp=85098145034&partnerID=8YFLogxK
U2 - 10.1002/onco.13633
DO - 10.1002/onco.13633
M3 - Article
C2 - 33301235
SN - 1083-7159
VL - 26
SP - 294
EP - 301
JO - Oncologist
JF - Oncologist
IS - 4
ER -