Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report

Guida, Michele; D'Alo', Alessandro; Mangia, Anita; Pinto, Federica; Sonnessa, Margherita; Albano, Anna; Sciacovelli, Angela Monica; Asabella, Artor Niccoli; Fucci, Livia

doi:10.3389/fonc.2020.01073

Cited by 12 publications

(9 citation statements)

References 21 publications

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“…Knowledge of somatostatin expression can be utilized for both diagnosis and treatment. A recent case report from Italy documented a metastatic MCC [ 26 ] patient who presented with loco-regional relapse after surgery and chemoradiotherapy. Octreoscan and IHC revealed increased expression of somatostatin receptors.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive Assessment of Somatostatin Receptors in Various Neoplasms: A Systematic Review

2022

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Somatostatin receptors (SSTR) are expressed in various neoplasms and can be targeted for both diagnostics as well as therapeutics. This systematic review aims to compile and discuss the prevalence of somatostatin receptor expression in various neoplasms. We performed a literature search from Google Scholar and PubMed using relevant keywords to look for all publicly available data regarding SSTR expression in various cancers. Both histopathological and radiographical studies were included for SSTR assessment. We found that many cancers express SSTR with varying prevalence. SSTR is now a well-established theranostics biomarker. We now have highly sensitive and specific diagnostic modalities like gallium 68 DOTATATE and copper 64 DOTATATE scans to screen for SSTR-2 and then target it therapeutically with lutetium 177 DOTATATE. A thorough understanding of SSTR expression in other tumors will open the channels for exploring potential SSTR targeting.

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Section: Resultsmentioning

confidence: 99%

Comprehensive Assessment of Somatostatin Receptors in Various Neoplasms: A Systematic Review

2022

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“…This study clearly provides evidence for the superiority of the combinational treatment of targeted radionuclide therapy and ICI over each single approach. Notably, the somatostatin analogue octreotide utilized in our PRRT approach may also add to the favorable response, as octreotide administered via intramuscular injection every 28 days in combination with avelumab demonstrates durable disease control in a patient with mMCC [ 33 ]. SSTR2 are not only expressed by neuroendocrine neoplastic cells, but also by some tumor-infiltrating B-cells.…”

Section: Discussionmentioning

confidence: 99%

Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma

et al. 2022

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Merkel cell carcinoma (MCC) is a neuroendocrine skin cancer of the elderly, with high metastatic potential and poor prognosis. In particular, the primary resistance to immune checkpoint inhibitors (ICI) in metastatic (m)MCC patients represents a challenge not yet met by any efficient treatment modality. Herein, we describe a novel therapeutic concept with short-interval, low-dose 177Lutetium (Lu)-high affinity (HA)-DOTATATE [177Lu]Lu-HA-DOTATATE peptide receptor radionuclide therapy (SILD-PRRT) in combination with PD-1 ICI to induce remission in patients with ICI-resistant mMCC. We report on the initial refractory response of two immunocompromised mMCC patients to the PD-L1 inhibitor avelumab. After confirming the expression of somatostatin receptors (SSTR) on tumor cells by [68Ga]Ga-HA-DOTATATE-PET/CT (PET/CT), we employed low-dose PRRT (up to six treatments, mean activity 3.5 GBq per cycle) at 3–6 weeks intervals in combination with the PD-1 inhibitor pembrolizumab to restore responsiveness to ICI. This combination enabled the synergistic application of PD-1 checkpoint immunotherapy with low-dose PRRT at more frequent intervals, and was very well tolerated by both patients. PET/CTs demonstrated remarkable responses at all metastatic sites (lymph nodes, distant skin, and bones), which were maintained for 3.6 and 4.8 months, respectively. Both patients eventually succumbed with progressive disease after 7.7 and 8 months, respectively, from the start of treatment with SILD-PRRT and pembrolizumab. We demonstrate that SILD-PRRT in combination with pembrolizumab is safe and well-tolerated, even in elderly, immunocompromised mMCC patients. The restoration of clinical responses in ICI-refractory patients as proposed here could potentially be used not only for patients with mMCC, but many other cancer types currently treated with PD-1/PD-L1 inhibitors.

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“…147 There have been reports of individual cases and small case series indicating that peptide-receptor radioligand therapy (PRRT) based on somatostatin expression may constitute an effective therapeutic concept if somatostatin receptors (SSTR) are detected on MCC cells in the tumors and metastases. [148][149][150] PRRT was either used as monotherapy or administered in combination with chemotherapy or immunotherapy. Somatostatin receptors can be detected via SSTR-PET/CT or SSTR-PET/MRT.…”

Section: Other Systemic Treatmentsmentioning

confidence: 99%

S2k Guideline – Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – Update 2022

Becker

Beer

DeTemple

et al. 2023

J Deutsche Derma Gesell

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SummaryMerkel cell carcinoma (MCC, ICD‐O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically‐mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.

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Somatostatin Receptors in Merkel-Cell Carcinoma: A Therapeutic Opportunity Using Somatostatin Analog Alone or in Association With Checkpoint Inhibitors Immunotherapy. A Case Report

Cited by 12 publications

References 21 publications

Comprehensive Assessment of Somatostatin Receptors in Various Neoplasms: A Systematic Review

Comprehensive Assessment of Somatostatin Receptors in Various Neoplasms: A Systematic Review

Short-Interval, Low-Dose Peptide Receptor Radionuclide Therapy in Combination with PD-1 Checkpoint Immunotherapy Induces Remission in Immunocompromised Patients with Metastatic Merkel Cell Carcinoma

S2k Guideline – Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – Update 2022

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