Evaluation of real-world treatment outcomes in patients with distant metastatic Merkel cell carcinoma following second-line chemotherapy in Europe

Abstract

Background and aimsMerkel cell carcinoma (MCC) is a rare, aggressive skin cancer; few treatments exist for patients with advanced disease. Once tumors metastasize to distant sites, patients generally receive chemotherapy, but response duration and progression-free survival (PFS) are typically short. Few studies have assessed the efficacy of second-line chemotherapy for metastatic MCC. Here, we studied outcomes in patients who received ≥ 2 lines of chemotherapy for metastatic MCC.Materials and methodsPatients in an MCC-specific registry diagnosed with stage IV MCC between November 1, 2004, and September 15, 2015, and treated with second-line or later chemotherapy were analyzed retrospectively. Patient records, including baseline characteristics, immunocompetent status, and responses to prior chemotherapy, were evaluated. Patients meeting eligibility criteria were followed through December 31, 2015.ResultsOf 29 patients with metastatic MCC and immunocompetent status who had received ≥ 2 lines of chemotherapy, 3 achieved a partial response, for an objective response rate (ORR) of 10.3% (95% CI, 2.2–27.4). In the overall population including patients with immunocompetent and immunocompromised status (n = 34), the ORR was 8.8% (95% CI, 1.9–23.7). The median duration of response was 1.9 months (range, 1.3–2.1 months; 95% CI, 1.3–2.1). In the immunocompetent population, median PFS and overall survival were 3.0 months (95% CI, 2.5–6.0) and 5.3 months (95% CI, 4.3–6.0), respectively.ConclusionsThe low response rates and limited durability confirm previous reports of the ineffectiveness of second-line or later chemotherapy in patients with metastatic MCC and provide a benchmark for assessing clinical benefit of new treatments.

Merkel cell carcinoma

“…In the 30 patients who also received second-line chemotherapy, the response rate was 23%, median progression-free survival was 61 days and median overall survival was 5.7 months 131 . Similar poor results of second-line chemotherapy were reported in another retrospective analysis of 34 European patients 131,132 .…”

Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program

“…4 5 MCC is considered a chemosensitive tumor, but responses to chemotherapy in patients with metastatic MCC (mMCC) are seldom durable. [6][7][8][9][10] In addition, commonly used platinum-based chemotherapy regimens incur significant toxicity, particularly in a population that largely comprise older patients. There is evidence that impairment of the immune system can contribute to the pathogenesis of MCC, providing a rationale for therapies that promote antitumor immune responses.…”

S2k guidelines for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) – update 2018

“…Response rates in these publications ranged from 23 % to 61 %, with higher response rates in the first‐line setting (53–61 %) than in second‐line therapy (23–45 %). The response duration was less than eight months, both in first‐ and second‐line treatment , . Given their high toxicity, combination therapies in particular require individual dose adjustments, especially in elderly patients who frequently have impaired liver and kidney function as well as a limited bone marrow reserve.…”