Treatment Outcomes in Patients with Metastatic Neuroendocrine Tumors: a Retrospective Analysis of a Community Oncology Database

Fisher, Mary L.; Pulgar, Sonia; Kulke, Matthew H.; Mirakhur, Beloo; Miller, Paul J.; Walker, Mark S.; Schwartzberg, Lee S.

doi:10.1007/s12029-018-0160-x

Cited by 8 publications

(10 citation statements)

References 37 publications

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“…Although multiple series [22–25] have documented the use of SSAs among patients with G3 NETs, this is, to our knowledge, the first study to formally report the survival outcomes associated with SSAs in an albeit small cohort of patients with well‐differentiated, G3 panNETs. The rationale to treat patients with G3 panNETs with somatostatin‐based therapies relies on the expression of somatostatin receptors, which has been described in small series to occur in up to 80% of G3 GEP‐NETs [26, 27].…”

Section: Discussionmentioning

confidence: 99%

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 99%

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

et al. 2020

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“…In the current study, a relatively high proportion of patients (64%) had CS at the time of GI NET diagnosis. Prior studies have reported a wide range of proportions of patients with NET and CS, ranging from 3% to 74% across studies . Halperin et al reported that 19% of those diagnosed with NET between 2000 and 2011 in SEER‐Medicare had CS within 6 months of NET diagnosis, with the percentage increasing over time .…”

Section: Discussionmentioning

confidence: 99%

“…In that study, CS was also shown to be associated with advanced disease , which was an eligibility requirement for patients in the current study. Using a U.S. cancer database, Fisher et al reported 43% of patients with metastatic NET had some CS symptoms . Pulgar et al reported 57% of patients with metastatic GEP NET had CS symptoms in an analysis of U.S. oncology electronic health records .…”

Section: Discussionmentioning

confidence: 99%

“…Dose modification occurred in 103 patients (38%), with a maximum of six instances of modification (supplemental online Table 1). The median (interquartile range) dose ever administered was 30 mg/4 weeks (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Supplemental online Figure 2 displays the patterns of octreotide dose changes observed in at least 1% of patients among those with known octreotide doses.…”

Section: Demographic and Clinical Characteristics At Baselinementioning

confidence: 99%

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Real-World Treatment Patterns and Clinical Outcomes in Advanced Gastrointestinal Neuroendocrine Tumors (GI NET): A Multicenter Retrospective Chart Review Study

Kulke¹,

Benson

Dasari

et al. 2019

The Oncologist

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Background We assessed treatment patterns and outcomes of patients with advanced gastrointestinal (GI) neuroendocrine tumors (NET) at four large tertiary referral centers in the U.S. Patients and Methods We performed a retrospective chart review of patients aged ≥18 years at advanced GI NET diagnosis, treated between July 2011 and December 2014. Index date was the histologically confirmed diagnosis date of locally advanced/metastatic GI NET. Data included baseline characteristics, treatment patterns, progression, death, and GI NET‐related health care resource utilization from index date through last contact or death. Time‐to‐event analyses, including treatment discontinuation, progression, and overall survival (OS), were performed using Kaplan‐Meier analysis. Results We identified 273 patients; 156 (57%) had primary ileum NET, and 174 (64%) had functional NET. First‐line treatments included somatostatin analog (SSA) alone (89%) or in combination (2%), liver‐directed therapy (LDT; 8%), and cytotoxic chemotherapy or interferon (2%). One hundred fifty‐five patients continued with second‐line therapy, including SSA alone (17%) or in combination (75%, with 3% combined with peptide receptor radionuclide therapy), LDT (4%), and other treatments (3%). Median time (months) to first‐line discontinuation was 154.0 for SSAs and 3.8 for cytotoxic chemotherapy. Overall median time to investigator‐assessed progression following treatment initiation was 30.3 months. Median OS (months) following first‐line initiation was 151.8 for all patients and 178.9 for first‐line SSA. Conclusion Our study illustrates the common use of SSAs in both first‐line and subsequent treatment of patients with GI NETs, as well as the relatively long survival durations and multiple additional treatments received by patients with this condition. Treatment pattern assessment at later times, following approval of newer treatments, is warranted. Implications for Practice This study, assessing treatment patterns over a period of up to 30 years, showed that SSAs, LDT, cytotoxic chemotherapy, and interferon are common treatments for advanced GI NETs. SSAs alone or in combination with other treatments were the most frequent therapy in first and subsequent lines. Patients in this study remained on SSAs long‐term, with median treatment duration of 12.8 years in first line. Treatment patterns should be assessed beyond this study's time period, given recent U.S. Food and Drug Administration approvals for additional treatments for GI NET, which will likely be incorporated in the continuum of care of patients.

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“…There are several publications describing real-world treatment patterns for GEP-NET [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. The majority of these studies are North American (mainly US), while a few are from Europe and other continents.…”

Section: Introductionmentioning

confidence: 99%

Treatment Patterns and Survival among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours in Sweden - a Population-based Register-linkage and Medical Chart Review Study

et al. 2019

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Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are neoplasms derived from the endocrine system in the gastrointestinal tract and pancreas. Treatment options include surgery; pharmacological treatments like somatostatin analogues (SSA), interferon alpha, molecular targeted therapy and chemotherapy; and peptide receptor radionuclide therapy.The objective of this study was to describe treatment patterns and survival among patients with metastatic GEP-NET grade 1 or 2 in Sweden.Methods: Data was obtained via linkage of nationwide registers. Patients diagnosed with metastatic GEP-NET grade 1 or 2 in Sweden between 2005 and 2013 were included (n=811; National population). In addition, medical chart review was performed for the subpopulation diagnosed at Sahlgrenska University Hospital, Gothenburg (n=127; Regional population). Treatment patterns, including treatment sequences, and overall survival were assessed.Results: Most patients had small intestinal NET (76%). In the regional population, 72% had grade 1 tumours; 50% had functioning tumours. The two most common first-line treatments were surgery (57%) and SSA (25%). After first-line surgery, 46% received SSA, while 40% had no further treatment. After first-line SSA, 52% received surgery, while 27% had no further treatment. Overall median survival time from date of diagnosis was 7.0 years (95% CI 6.2-not reached). Among patients with distant metastases, pancreatic NET (vs. small intestinal NET) was associated with poorer survival (HR 1.9; 95% CI 1.1-3.3), as were liver metastases (HR 3.2; 95% CI 1.5-7.0).Conclusions: First-line surgery was typically followed by SSA or no further treatment. Among patients with distant metastases, pancreatic NET or liver metastases were associated with a poorer survival.

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Treatment Outcomes in Patients with Metastatic Neuroendocrine Tumors: a Retrospective Analysis of a Community Oncology Database

Cited by 8 publications

References 37 publications

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

Somatostatin Analogs for Pancreatic Neuroendocrine Tumors: Any Benefit When Ki-67 Is ≥10%?

Real-World Treatment Patterns and Clinical Outcomes in Advanced Gastrointestinal Neuroendocrine Tumors (GI NET): A Multicenter Retrospective Chart Review Study

Treatment Patterns and Survival among Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumours in Sweden - a Population-based Register-linkage and Medical Chart Review Study

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