High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma. (1st February 2021) - Akaike, T.
Summary: Background: Merkel cell carcinoma (MCC) is an aggressive, high‐grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low‐ and moderate‐grade NETs that express somatostatin receptors (SSTRs). Objectives: To assess SSTR expression and the efficacy of SSAs in mMCC, a high‐grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible ( n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression‐free survival (PFS) of ≥ 120 days after initiation of SSA. Results: Thirty‐three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response‐evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152–358). Twelve of 19 patients did not have a response‐evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143–1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. Conclusions: In contrast to other high‐grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side‐effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.