Efficacy of somatostatin analog (SSA) monotherapy for well-differentiated grade 3 (G3) gastroenteropancreatic neuroendocrine tumors (NETs).

McGarrah, Patrick Walsh; Hobday, Timothy J.; Starr, Jason S.; Kendi, Ayse T.; Graham, Rondell P.; Sonbol, Mohamad Bassam; Halfdanarson, Thorvardur R.

doi:10.1200/jco.2020.38.4_suppl.617

Cited by 11 publications

(15 citation statements)

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“…Other treatment regimens have been used in NET G3, including sunitinib, immune checkpoint inhibitors, and SSAs [10,31,32]. In a separate Mayo Clinic study, treatment response and survival were assessed in patients with NET G3 who received SSA (n = 14), finding ORR of 14.3%, DCR of 64.3%, and mPFS of 4.4 months (95% CI, 2.9-24) [10].…”

Section: Discussionmentioning

confidence: 99%

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Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

et al. 2021

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Introduction Recent classification of neuroendocrine neoplasms has defined well‐differentiated high‐grade neuroendocrine tumors (NET G3) as a distinct entity from poorly differentiated neuroendocrine carcinoma. The optimal treatment for NET G3 has not been well‐described. This study aimed to evaluate metastatic NET G3 response to different treatment regimens. Materials and Methods This was a retrospective study of patients with NET G3 within the Mayo Clinic database. Patients’ demographics along with treatment characteristics, responses, and survival were assessed. Primary endpoints were progression‐free survival (PFS) and overall survival. Secondary endpoints were objective response rate (ORR) and disease control rate (DCR). Results Treatment data was available in 30 patients with median age of 59.5 years at diagnosis. The primary tumor was mostly pancreatic (73.3%). Ki‐67 index was ≥55% in 26.7% of cases. Treatments included capecitabine + temozolomide (CAPTEM) (n = 20), lutetium 177 DOTATATE (PRRT; n = 10), Platinum‐etoposide (EP; n = 8), FOLFOX (n = 7), and everolimus (n = 2). CAPTEM exhibited ORR 35%, DCR 65%, and median PFS 9.4 months (95% confidence interval, 2.96–16.07). Both EP and FOLFOX showed similar radiographic response rates with ORR 25.0% and 28.6%; however, median PFS durations were quite distinct at 2.94 and 13.04 months, respectively. PRRT had ORR of 20%, DCR of 70%, and median PFS of 9.13 months. Conclusion Among patients with NET G3, CAPTEM was the most commonly used treatment with clinically meaningful efficacy and disease control. FOLFOX or PRRT are other potentially active treatment options. EP has some activity in NET G3, but responses appear to be short‐lived. Prospective studies evaluating different treatments effects in patients with NET G3 are needed to determine an optimal treatment strategy. Implications for Practice High‐grade well‐differentiated neuroendocrine tumors (NET G3) are considered a different entity from low‐grade NET and neuroendocrine carcinoma in terms of prognosis and management. The oral combination of capecitabine and temozolomide is considered a good option in the management of metastatic NET G3 and may be preferred. FOLFOX is another systemic option with reasonable efficacy. Similar to other well‐differentiated neuroendocrine tumors, peptide receptor radionuclide therapy seems to have some efficacy in these tumors.

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Section: Discussionmentioning

confidence: 99%

“…In this retrospective analysis, we aim to evaluate the clinical outcomes of patients with NET G3 treated with different cytotoxic regimens at Mayo Clinic. SSA use in NET G3 is discussed in a separate retrospective Mayo Clinic study [10]. [11].…”

Section: Introductionmentioning

confidence: 99%

Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

et al. 2021

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“…Limited data point to PRRT efficacy even in G3 NEN with high SSTR expression ( Lithgow et al 2021 ), which is consistent with the early plateau we observed in the relationship between Ki-67 and PFS. On the other hand, pivotal SSA studies included only patients with Ki-67 <10%, and small series indicate minimal effect in patients with G3 tumours ( McGarrah et al 2020 , Lithgow et al 2021 , Merola et al 2021 ). Interestingly, the European Society of Medical Oncology guidelines propose the use of everolimus before PRRT in G2 patients with Ki-67 >10% ( Pavel et al 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Treatment efficacy in a metastatic small intestinal neuroendocrine tumour grade 2 cohort

Papantoniou

Grönberg

Thiis‐Evensen

et al. 2023

Endocrine-Related Cancer

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Small intestinal neuroendocrine tumours (Si-NET) are often studied as a uniform group. Proliferation index Ki-67 influences prognosis and determines tumour grade. We hypothesized that Si-NET grade 2 (G2), which have a higher Ki-67 than G1 tumours, might benefit less from established treatments for metastatic disease. We conducted a retrospective cohort study of 212 patients with metastatic Si-NET G2 treated in two Swedish hospitals during 20 years (2000-2019). Median cancer-specific survival (CSS) on first-line somatostatin analogues (SSA) was 77 months. Median progression-free survival (PFS) was 12.4 months when SSA was given as monotherapy, and 19 months for all patients receiving first-line SSA. PFS after SSA dose escalation was 6 months in patients with radiological progression. Treatment efficacies of SSA and peptide-receptor radionuclide treatment (PRRT) were studied separately in patients with Ki-67 of 3-5%, 5-10% and 10-20%. For SSA, PFS was significantly shorter at higher Ki-67 levels (31, 18 and 10 months, respectively) while there was only a minor difference in PFS for PRRT (29, 25 and 25 months). Median PFS for sequential treatment with interferon-alpha (IFNa), everolimus and chemotherapy was 6, 5 and 9 months. IFNa seemed to be effective in tumours with low somatostatin-receptor expression. In conclusion, established treatments appeared effective in Si-NET G2, despite their higher proliferation index compared to G1 tumours. However, efficacy of SSA but not PRRT was reduced at higher Ki-67 levels. SSA dose escalation provided limited disease stabilization.

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“… 25 Data regarding the use of SSAs in G3 NETs is scarce and SSAs were historically not recommended for high-grade NENs. McGarrah et al 26 reported a median PFS of 4.4 months and a disease control rate of 50% in 14 patients with G3 NETs receiving single-agent SSAs in any line of therapy. They concluded SSAs may present an attractive option given their favorable side-effect profile, a conclusion that is supported by our results.…”

Section: Discussionmentioning

confidence: 99%

Well-Differentiated Grade 3 Neuroendocrine Tumors

Boutin¹,

Mathews²,

Badesha³

et al. 2022

Pancreas

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Objectives:We evaluated a population-based cohort of metastatic welldifferentiated grade 3 gastroenteropancreatic neuroendocrine tumors (G3 NETs) to describe their characteristics, prognosis, and treatment outcomes. Methods:The British Columbia provincial database was queried for G3 NETs diagnosed 2004 to 2021, and charts were reviewed to describe clinical features and outcomes.Results: Forty-one patients were identified, most were diagnosed with pancreatic (58.5%) or midgut (26.8%) primary tumor and Ki-67 was less than 55% in 68.3%. The primary was resected in 19 (46.3%) with median disease-free survival of 25.2 months. Once metastatic, patients received a median of one line of systemic therapy. Median overall survival with metastatic disease was 33.8 months. Median progression-free survival was longest in patients treated with capecitabine-temozolomide (20.6 months) or somatostatin analogs (7.9 months), while etoposide-platinum provided little benefit (2.4 months). Limited data of efficacy for targeted therapies and radionuclide therapy was available. Seven patients (17.1%) were also treated with local therapies, which were associated with improved overall survival (median not reached, hazard ratio, 0.23; P = 0.012).Conclusions: Capecitabine-temozolomide and somatostatin analogs were associated with clinically meaningful benefit, and use of local therapies provided benefits in selected patients. Multidisciplinary discussion is essential to optimize individual outcomes in this heterogeneous population.

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Efficacy of somatostatin analog (SSA) monotherapy for well-differentiated grade 3 (G3) gastroenteropancreatic neuroendocrine tumors (NETs).

Cited by 11 publications

References 0 publications

Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

Treatment Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors

Treatment efficacy in a metastatic small intestinal neuroendocrine tumour grade 2 cohort

Well-Differentiated Grade 3 Neuroendocrine Tumors

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