High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma

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 metastaticMCC(mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-gradeNETs that express somatostatin receptors (SSTRs). Objectives To assessSSTRexpression and the efficacy ofSSAs inmMCC, a high-gradeNET. MethodsIn this retrospective study of 40 patients withmMCC,SSTRexpression was assessed radiologically by somatostatin receptor scintigraphy (SRS;n= 39) and/or immunohistochemically when feasible (n= 9). Nineteen patients (18 hadSRSuptake inMCCtumours) were treated withSSA. Disease control was defined as progression-free survival (PFS) of >= 120 days after initiation ofSSA. Results Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) ofSRSuptake. Of 19 patients treated withSSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a medianPFSof 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 (medianPFSof 429 days, range 143-1757). The degree ofSSTRexpression (determined bySRSand/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. Conclusions In contrast to other high-gradeNETs,mMCCtumours appear frequently to expressSSTRs.SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting ofSSTRs usingSSAor other novel approaches should be explored further formMCC.