Systemic treatment of patients with inoperable and metastatic Merkel cell carcinoma: A multicenter study.
Authors: Dudzisz-Śledź Monika , Sobczuk Pawel , Kozak Katarzyna , Switaj Tomasz , Kosela-Paterczyk Hanna , Czarnecka Anna Malgorzata , Falkowski Slawomir , Rogala Pawel , Morysinski Tadeusz , Spalek Mateusz , Zdzienicki Marcin , Goryn Tomasz , Zietek Marcin , Cybulska-Stopa Bozena , Klek Stanislaw , Szumera-Cieckiewicz Anna , Rutkowski Piotr 
Published: June 2021

e21521

Background: Merkel cell carcinoma (MCC) is an uncommon, aggressive neuroendocrine skin cancer. The prognosis in the unresectable and metastatic setting is very poor. Distant metastases develop in more than 30%. Chemotherapy (CHT), the previous mainstay of treatment, is associated with the high response rates (RR) of limited duration. The main cytotoxic drugs have been platinum derivatives, taxoids, anthracyclines, and etoposide. The standard systemic treatment for this disease has changed in the last few years. Immunotherapy (IO) is currently the basis of systemic therapy in the metastatic setting. This study aimed to analyze outcomes for unresectable and metastatic MCC pts treated in routine clinical practice, mostly before the era of IO availability. Methods: We conducted the retrospective analysis of data from 36 MCC pts in unresectable (n= 23) and metastatic (n=13) settings treated in three oncological centers, diagnosed between 01/2010 and 12/2019, with data cut-off on 31/12/2020. The data collected included epidemiological and clinical information. Survival analyses were performed using the Kaplan-Meier method and log-rank test. Results: The median patient age at diagnosis was 72 years (57-88); 58.3% were male. The most common primary tumor (PT) locations were lower limbs (41.7%), head and neck (30.6%), and upper limbs (16.7%). In 63.9% the PT was located in the sun-exposed skin. The most common location of distant metastases were nonregional lymph nodes (n=9) and lungs (n=3). Thirty-six pts received 1st line CHT with the median progression-free survival (mPFS) of 5.3 months (95%CI 2.88-7.7) and objective response of 61.1%, with 13.9% complete responses (CR). The most commonly used regimens were platinum-based and anthracycline-based regimens (n=26). Disease progression (PD) was observed in 91.7% of pts treated with 1st line CHT. Twenty-one pts received 2nd line therapy, IO (n=14), or CHT (n=7), with PD in 19 pts (90.6%), mPFS 2.83 months (95% CI 0.59-5.06) and RR of 33.3% (0% CR). 13 pts were treated with avelumab (AVE), all in the 2nd line, with RR of 38.5% (0% CR). The mPFS in the 2nd line was 5 months (95%CI 0-11.46) on AVE compared to 2.82 (95%CI 0.46-5.19) on CHT (HR 0.65, 95%CI 0.25-1.70, p=0.378). During 1st line systemic therapy, 16 pts underwent palliative surgery (n=7, 19.4%) or received radiation therapy (RT) (n=9, 25%), and during 2nd line, one patient was treated with surgery, and five pts received RT. The median overall survival was 10.38 months (95% CI 2.90-17.87). Local treatment did not improve the treatment outcomes in the 1st (p=0.119) nor 2nd line (p=0.821). Conclusions: Our results confirm the poor prognosis of pts with unresectable and metastatic MCC. The response rates and median PFS for CHT in the 1st and 2nd line setting are consistent with historical data. The treatment with AVE in the 2nd line allows achieving better results, similar to the results reported in the clinical trials.