Systematic literature review of efficacy, safety and tolerability outcomes of chemotherapy regimens in patients with metastatic Merkel cell carcinoma

Abstract

Aim:Merkel cell carcinoma (MCC) is a rare neuroendocrine, cutaneous malignancy with poor prognosis once metastasized. The aim of this study was to conduct a systematic literature review to assess clinical outcomes associated with chemotherapy regimens in metastatic MCC.>Materials & methods:Embase®, MEDLINE®, MEDLINE®-In-Process and CENTRAL were searched for studies published in January 2016.Results & conclusion:Overall, the literature on chemotherapy in patients with metastatic MCC is sparse, with most studies being case series/reports. Across all studies, response rates ranged from 20 to 61%, with higher response rates in first-line setting (53–61%) versus second-line setting (23–45%). Among responders, duration of response was short (≤8 months) in both first- and second-line settings. There is a need for novel agents that can induce durable responses in metastatic MCC.

Merkel cell carcinoma

“…Until 2016, before the introduction of immunotherapy, the most common treatments for metastatic MCC not amenable to surgery were chemotherapeutic regimens often used for other small-cell carcinomas; these include platinum-based regimens, etoposide 130 , taxanes and anthracyclines, either alone or in various combinations. The rationale for this approach was the observation that MCC has a cell morphology similar to that of other small-cell carcinomas as well as the fact that this treatment led to clinically meaningful responses in a subset of patients with MCC; however, these responses were short-lived.…”

“…In the first study to report immune-checkpoint blockade using the anti-PD1 antibody pembrolizumab in patients with advanced-stage MCC, the response rate was 56% 136 . The rate of progression-free survival at 6 months was 67%, compared with 24% for chemotherapy, based on historical data 130,131 . These promising results led to the inclusion of pembrolizumab as a systemic therapy option for disseminated disease in the 2017 NCCN guidelines for MCC management 81 .…”

Molecular and immune targets for Merkel cell carcinoma therapy and prevention

“…On the basis of the histopathologic findings and resulting staging, lymphadenectomy and adjuvant radiation therapy may follow. For metastatic MCC, cytotoxic chemotherapy including anthracyclines, platinums and/or etoposide and/or topotecan are utilized most commonly . Response rates to chemotherapy range from 20% to 61%, with higher response rates in the first‐line setting .…”

“…For metastatic MCC, cytotoxic chemotherapy including anthracyclines, platinums and/or etoposide and/or topotecan are utilized most commonly . Response rates to chemotherapy range from 20% to 61%, with higher response rates in the first‐line setting . Among responders, the duration of response is short, that is, less than 8 months in first and second line settings .…”

“…The lack of molecular specificity, and the early development of resistance to chemotherapies, has limited their efficacy. For these reasons, chemotherapy is now considered to have only a palliative role in MCC …”