Real-world treatment outcomes in patients with metastatic Merkel cell carcinoma treated with chemotherapy in the USA

Abstract

aim: This retrospective study of patients in the USA with metastatic Merkel cell carcinoma (mMCC) aimed to assess patient responses to second-line and later (2L+) and first-line (1L) chemotherapy. Patients & methods: Out of 686 patients with MCC identified in The US Oncology Network, 20 and 67 patients with mMCC qualified for the 2L+ and 1L study, respectively; the primary analysis population was restricted to immunocompetent patients. Results: In the 2L+ primary analysis population, objective response rate (ORR) was 28.6%, median duration of response (DOR) was 1.7 months and median progression-free survival was 2.2 months. In the 1L primary analysis population, ORR was 29.4%, median DOR was 6.7 months and median progression-free survival was 4.6 months. conclusion: The low ORR and brief DOR underscore the need for novel therapies. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer that occurs most frequently in elderly and immunocompromised patients [1][2][3]. There are approximately 1500 cases of MCC per year in the USA, and the incidence has dramatically increased over the last 20 years [4]. MCC typically presents as painless growths that are clinically unremarkable in appearance and are usually found on sun-exposed areas, such as the head and neck [2,3]. These tumors grow rapidly and tend to metastasize early and frequently to local regions of the body, leading to a relatively poor prognosis with this aggressive disease [2,3,5]. Among patients diagnosed with local or regional disease, the reported rates of recurrence range from 43 to 48% [6,7]. The 5-year overall survival (OS) rate is 40% [1] and the mortality rate with MCC is greater than that with other skin cancers, including melanoma [4].Recently, avelumab, a human IgG1 anti-programmed death-ligand 1 (PD-L1) monoclonal antibody, was approved by the US FDA as the first and only approved treatment for patients with metastatic MCC (mMCC) [8]. Before this approval, there was no evidence-based standard therapeutic regimen for mMCC. The National Comprehensive Cancer Network treatment guidelines for mMCC [9] are based on those used for small cell lung cancer, as both are aggressive and poorly differentiated cancers [10]. Treatments typically include platinum agents, such as carboplatin or cisplatin with or without etoposide or topotecan, and are associated with high toxicity [9,11]. Although MCC is generally considered a chemosensitive tumor, responses to chemotherapy in metastatic disease are For reprint orders, please contact: reprints@futuremedicine.com

Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma

“…Our median PFS of 9.1 months for patients receiving first-line treatment exceeds that previously reported with chemotherapy. 4,5 Our safety analysis showed that avelumab was generally tolerable. These findings suggest overall improvement of outcomes with immune checkpoint inhibitors vs chemotherapy in patients with mMCC.…”

Recent Therapeutic Advances and Change in Treatment Paradigm of Patients with Merkel Cell Carcinoma

“…Two‐year PFS and OS rates were 26% (29% at 1 year) and 36% (50% at 1 year), respectively. Median PFS was 2.7 months and median OS was 12.6 months, which is highly favorable for patients in this setting considering historical chemotherapy data (Table ) . Durable antitumor efficacy was observed across all patient subgroups (MCPyV‐positive, MCPyV‐negative, PD‐L1‐positive, and PD‐L1‐negative patients), although there was a trend toward a greater response rate in patients with PD‐L1‐positive as compared with PD‐L1‐negative tumors (36% vs 19%, respectively) .…”

“…Avelumab is a fully human IgG1 anti-PD-L1 antibody that preserves antibody-mediated cytotoxicity [49]. The efficacy of avelumab was investigated in the JAVELIN Merkel 200 phase II trial, which has two main parts (A and B) [3,44,50,51]. Durable antitumor efficacy was observed across all patient subgroups (MCPyV-positive, MCPyV-negative, PD-L1-positive, and PD-L1-negative patients), although there was a trend toward a greater response rate in patients with PD-L1positive as compared with PD-L1-negative tumors (36% vs 19%, respectively) [38,50].…”

Merkel Cell Polyomavirus Small Tumor Antigen Activates Matrix Metallopeptidase-9 Gene Expression for Cell Migration and Invasion

“…Our study is the first approach to investigate the therapeutic potential of matrix metalloproteinases in MCC. Standard chemotherapy regimens for metastatic MCC include carboplatin or cisplatin with etoposide and topotecan (69). Because recent FDA approvals of Avelumab and Pembrolizumab represent the only approved treatment option for metastatic MCC (70, 71), it is necessary to evaluate and develop the preclinical activity of efficient and economical chemotherapeutics through retrospective analysis for both MCV-negative and positive MCC patients.…”