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

Abstract

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.

Targeting the expression of T antigens with selinexor (KPT‐330) shows promise for Merkel cell polyomavirus‐positive Merkel cell carcinoma treatment

“…A previous study by Akaike et al . examining the use of somatostatin analogues to treat metastatic MCC with high somatostatin receptor expression found that these receptor analogues led to clinically significant disease control 8 . Taken together, our results demonstrate that evaluating MCC tumour‐targeted therapies must continue.…”

Positron Emission Tomography in Merkel Cell Carcinoma

“…In the largest cohort study, 85% of MCC patients ( n = 39) had at least some degree of 111 In-pentetreotide uptake in SSTR scintigraphy, with the majority (75%) showing low to medium tracer uptake. However, the SSTR expression status, assessed by scintigraphy, did not significantly correlate with clinical outcomes of SSTR-targeted therapy [ 73 ].…”

There is still a place for tumour‐targeted therapies in Merkel cell carcinoma in the era of immune checkpoint inhibitors

“…Their use in clinical trials is increasingly recognized by regulatory authorities, clinicians and patients because they help to indicate whether the impact of an intervention is comprehensively assessed. 4 In this issue of the BJD, Bhat et al 5 use qualitative research to assess the impact of CTCL on patients' daily lives and to identify the most meaningful aspects in assessing QoL in CTCL. This is achieved by evaluating existing QoL instruments (generic, skin specific and disease specific).…”

“…In this issue of the BJD, Akaike et al 4 report the Seattle experience with targeting somatostatin receptors (SSTRs), transmembrane proteins frequently expressed by neuroendocrine cancers. SSTR expression was assessable by either imaging or immunohistochemistry in 40 patients with MCC, of whom 19 were evaluable for their response to a somatostatin analogue (octreotide long-acting release).…”

“…Signature 1, a clock-like signature, correlates with age and is thought to arise from spontaneous deamination of 5-methylcytosine during cell division. 4 Signature 7 reflects environmental UVR-specific mutation damage. Previous studies show that signature 7 is more predominant in BRAF, NRAS and NF1 melanomas compared with W3 tumours.…”