Avelumab for advanced Merkel cell carcinoma in the Netherlands: a real-world cohort

Abstract

BackgroundMerkel cell carcinoma (MCC) is associated with high recurrence rates and poor survival when metastatic disease is present. The immune checkpoint inhibitor avelumab has shown high response rates (RRs) and durable responses in patients with advanced MCC (aMCC) in clinical trials. To date, only results from clinical trials, patients treated in an expanded access program and very small numbers of patients have been reported. In this study, detailed real-world efficacy and toxicity data of avelumab in patients with aMCC are reported.MethodsPatients with aMCC treated in four dedicated referral centers in the Netherlands were analyzed from February 2017 until December 2019. Patients were included if they had received at least one administration of avelumab, regardless of previous lines of therapy. Patient data were collected retrospectively from patient records. Primary endpoints were response rate (RR) and duration of response (DOR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity.ResultsFifty-four patients received avelumab. Eight (15%) patients had locally advanced disease (laMCC). In 40 (74%) patients, avelumab was first-line treatment, these included all patients with laMCC. The median follow-up was 8.9 (range 0.5–35.9) months. RR was 57% (n=31) with 24% (n=13) of patients achieving a complete response. The median DOR was 8.4 (range 1.3–22.1) months and 23 (43%) patients had an ongoing response at the end of the study. The median PFS was 8.6 (95% CI 1.6–15.5) months, and the median OS was 25.8 (95% CI 9.1–42.4) months. Six (11%) patients experienced grade 3 toxicity. No grade 4–5 toxicity was seen.ConclusionsIn this real-world cohort, clinical efficacy and toxicity outcomes in clinical practice were in line with results from clinical trials and showed relatively high RRs and durable responses in patients with aMCC.

Real-World Clinical Outcomes with First-Line Avelumab in Locally Advanced/metastatic Merkel Cell Carcinoma in the USA: SPEAR-Merkel

“…Nearly all (96.4%) in our study were immunocompetent, as were patients in clinical trials [8,12,17,18]. However, proportions of patients with immunocompromised status have ranged from 6 to 30% across other real-world studies [8,9,11,12,[19][20][21]. Two of these studies investigated patients treated with avelumab.…”

"Present and future of immunotherapy in Neuroendocrine Tumors"

“…Spassova et al [109] in their retrospective study found that immunocompetent patients responded better than ones with hematological malignancies or under immunosuppressive drugs, whereas the type of drug was not found to be predictor of response. Levy et al [111] showed that for avelumab, real-life data appear to be in line with results from clinical trials in terms of efficacy and toxicity. DOR in their cohort was 8.4 months, but with 43% of the patients having ongoing response at the end of the study.…”

“…While initial evidence is available from clinical trials, fewer real-life data are available on ICIs in MCC patients. Few authors have described experience with such drugs in MCC so far [108][109][110][111]. In the mentioned real-life studies, which comprise cohorts of patients treated with either avelumab, pembrolizumab or nivolumab plus ipilimumab, response rates ranged between 39-57%, with the best one found in a cohort of only avelumab-treated patients [111].…”

Merkel Cell Carcinoma: New Trends

“…In 71% of responders, there was a durable effect of more than one year. Experience from daily practice showed higher response rates of 47–57% and complete response in almost 25% of the patients, albeit that the duration of response was shorter (median 8 months) [ 80 , 81 ].…”

“…Toxicities more specific for immunotherapy include autoimmune endocrine dysfunctions, pneumonitis, colitis, and hepatitis [ 86 , 87 ]. Reported overall incidence of adverse effects for avelumab was 28–46%, of which 8–9% were grade 3–4 adverse reactions [ 80 , 83 ]. In the study with pembrolizumab as first line for advanced and metastatic MCC, treatment-related adverse events of any grade occurred in 48 of 50 (96%) patients, of which 14 (28%) were grade 3 or higher.…”