PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma

Raiza Gandola, Mercer University College of Pharmacy

Merkel Cell Carcinoma (MCC), considered a rare and aggressive skin cancer, arises from the uncontrolled growth of Merkel cells in the skin. It is classified as stage 0 – IV based on primary tumor size and presence of lymph node and metastasis. A cancer that normally affects those over 65 years of age or those immunocompromised, only about 1,500 cases are diagnosed per year in the United States. However, it is recommended that these patients undergo aggressive treatment as MCC has the potential to be lethal. [1]

The Skin Cancer Foundation states primary treatment for MCC involves surgical incision, radiation, and chemotherapy. The latest research on treatment for MCC, which focuses on blocking receptors that can inhibit production of T cells, is considered to show promising results. One such agent is Keytruda® (pembrolizumab), which works by blocking an immune-inhibiting receptor called programmed death-1 (PD-1), thus allowing the release of T cells to attack cancer cells. [2]

Title: PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma
Design Multi-center, phase II, non-controlled study; N= 26
Objective To determine the clinical efficacy of pembrolizumab as first systemic therapy for patients with advanced Merkel-cell carcinoma
Study Groups Pembrolizumab 2 mg/kg
Methods Adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy were to receive pembrolizumab at a dose of 2 mg/kg every three weeks.
Duration November 2014 to February 2016
Primary Outcome Measure Objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1
Baseline Characteristics   Patients with virus-positive tumors Patients with virus-negative tumors
Mean age, y 67.5 76.3
Male, n (%) 13 (76) 3 (33)
Disease stage at study entry, n (%)    
     IIIB 2 (12) 0
     IV 15 (88) 9 (100)
Previous duration of disease, weeks 71.3 35.2
Results A total 14 out of 26 patients had a confirmed response (four with a complete response and 10 with a partial response), representing an objective response rate of 56% [95% confidence interval (CI) (35-76)]
Adverse Events Common Adverse Events: Fatigue (46%) and lab abnormalities (23%)
Serious Adverse Events: Myocarditis (7.7%) and elevated levels of alanine aminotransferase (ALT) and aspartate aminotransferases (AST) (7.7%)
Percentage that Discontinued due to Adverse Events: 7.7%
Study Author Conclusions First-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors


The results of this study offer an alternative option for patients with advanced MCC, when standard of treatment does not always extend survival. One limitation to this study is the small population size, diminishing its usefulness to the general population. However, as this is a disease that does not affect many, finding a large patient population may prove difficult. The toxic effects seen in the elderly patient population are something to consider as myocarditis can lead to irregular heart rhythms, and abnormal AST and ALT levels suggest liver damage.



  1. Nghiem P, Kulikauskas R, Yelistratova L, et al. Merkel Cell Carcinoma: Information for Patients and their Physicians. Seattle Multidisciplinary MCC Team. http://www.merkelcell.org/. Accessed July 6, 2016.
  2. Sarnoff D. Merkel Cell Carcinoma-Treatment Options. Skin Cancer Foundation. http://www.skincancer.org/skin-cancer-information/merkel/treatment. Accessed on July 12, 2016.

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