scholarly journals Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy

2019 ◽  
Vol 37 (9) ◽  
pp. 693-702 ◽  
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Evan J. Lipson ◽  
William H. Sharfman ◽  
Ragini R. Kudchadkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell ◽  
First Line ◽  
Median Response ◽  
Programmed Cell Death 1

PURPOSE Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus–positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1–positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION Here, we present the longest observation to date of patients with aMCC receiving first-line anti–programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

scholarly journals Avelumab for the treatment of patients with Merkel cell carcinoma

2020 ◽  
pp. 94-100
Author(s):  
K. V. Orlova ◽  
N. N. Petenko ◽  
V. V. Nazarova ◽  
L. V. Demidov
Keyword(s):  
Overall Survival ◽  
Cell Death ◽  
Programmed Cell Death ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Merkel Cell Carcinoma ◽  
Objective Response ◽  
Locally Advanced ◽  
Merkel Cell

Merkel cell carcinoma is a rare and aggressive skin tumor that is difficult to treat even at early stages. Treatment approaches for advanced disease are limited and standard chemotherapy provides short-lived disease control in half of patients without significant impact on the overall survival. The new immunotherapy with anti-PD-1/PD-L1 inhibitors allows to improve clinical outcomes of this disease. Avelumab is a fully human IgG1 monoclonal anti- PD-L1 antibody that blocks the interaction between programmed cell death ligand 1 (PD-L1) on tumor cells and programmed cell death-1 receptor (PD-1) on T cells, thereby elimination immunosuppression in the tumor microenvironment. Avelumab provides disease control in 43,2% of the patients with metastatic/locally advanced unresectable Merkel cell carcinoma for the second and subsequent lines treatment with the objective response rate (ORR) 33%. The response was ongoing for ≥ 6 months in 86% of patient with median duration of response 40,5 months. Responses occurred irrespectively of PD-L1 expression and presence of polyomavirus in tumor cells (MCPyV), 3-year overall survival rate reached 32%. Avelumab is more effective for the first line of treatment, providing the disease control in 78,6% the patients with ORR 71,5% lasting for ≥ 6 months. Treatment is well tolerated for the first, second and subsequent lines, demonstrating the adequate safety profile. The most common adverse events were fatigue, diarrhea and nausea. There were 7 patients in Russia treated with avelumab for metastatic/locally advanced unresectable Merkel cell carcinoma.

Merkel cell carcinoma showing regression after biopsy: Evaluation of programmed cell death 1-positive cells

2015 ◽  
Vol 42 (5) ◽  
pp. 496-499 ◽  
Author(s):  
Noriki Fujimoto ◽  
Gen Nakanishi ◽  
Miho Kabuto ◽  
Toshiaki Nakano ◽  
Hikaru Eto ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell ◽  
Programmed Cell Death 1

Durable tumor regression and overall survival (OS) in patients with advanced Merkel cell carcinoma (aMCC) receiving pembrolizumab as first-line therapy.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 9506-9506 ◽  
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Evan J. Lipson ◽  
William Howard Sharfman ◽  
Ragini Reiney Kudchadkar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Tumor Regression ◽  
Merkel Cell ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals TdT Expression Is a Marker of Better Survival in Merkel Cell Carcinoma, and Expression of B-Cell Markers Is Associated With Merkel Cell Polyomavirus

2020 ◽  
Vol 154 (1) ◽  
pp. 38-47
Author(s):  
Mai P Hoang ◽  
Piotr Donizy ◽  
Cheng-Lin Wu ◽  
Janusz Kopczynski ◽  
Malgorzata Pieniazek ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Fisher Exact Test ◽  
Stem Cell Markers ◽  
Merkel Cell ◽  
Exact Test ◽  
Cell Markers

Abstract Objectives Merkel cell carcinoma is a rare but very aggressive cutaneous tumor. We evaluated the prognostic potential of B-cell markers (terminal deoxynucleotidyl transferase [TdT], PAX5, CD117), follicular stem cell markers (CK15, CK19), p63, p53, RB, and Merkel cell polyomavirus (MCPyV; CM2B4) in 136 primary cutaneous Merkel cell carcinomas. Methods Clinical, histopathologic, and immunohistochemical analyses were performed. The results were correlated with patient outcomes by Fisher exact test, log-rank tests, and Cox multivariate models. Results By Fisher exact test, although TdT significantly correlated with both lack of progression (P = .0087) and alive status (P = .0056), MCPyV status correlated only with alive status (P = .031). In univariate analyses, TdT, MCPyV, and RB significantly correlated with improved overall survival, whereas p63 and CK15 correlated with worse overall survival. However, in multivariate analyses, only TdT expression remained as an independent predictor of improved overall survival, Merkel cell carcinoma-specific survival, and progression-free survival. By linear regression analyses, significant correlations between MCPyV vs TdT, PAX5, and CD117 were observed. Conclusions TdT expression is a potential marker of better survival in Merkel cell carcinoma. Expression of B-cell markers is associated with MCPyV, suggesting that clonal viral integration might play a role in the expression of these markers.

scholarly journals PD-L1 Expression in the Merkel Cell Carcinoma Microenvironment: Association with Inflammation, Merkel Cell Polyomavirus, and Overall Survival

2013 ◽  
Vol 1 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Evan J. Lipson ◽  
Jeremy G. Vincent ◽  
Myriam Loyo ◽  
Luciane T. Kagohara ◽  
Brandon S. Luber ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Merkel Cell Polyomavirus ◽  
Merkel Cell

scholarly journals Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma

2021 ◽  
Vol 9 (4) ◽  
pp. e002478
Author(s):  
Paul Nghiem ◽  
Shailender Bhatia ◽  
Evan J Lipson ◽  
William H Sharfman ◽  
Ragini R Kudchadkar ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Stable Disease ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Merkel Cell ◽  
First Line ◽  
Median Response

BackgroundMerkel cell carcinoma (MCC) is an aggressive skin cancer associated with poor survival. Programmed cell death-1 (PD-1) pathway inhibitors have shown high rates of durable tumor regression compared with chemotherapy for MCC. The current study was undertaken to assess baseline and on-treatment factors associated with MCC regression and 3-year survival, and to explore the effects of salvage therapies in patients experiencing initial non-response or tumor progression after response or stable disease following first-line pembrolizumab therapy on Cancer Immunotherapy Trials Network-09/KEYNOTE-017.MethodsIn this multicenter phase II trial, 50 patients with advanced unresectable MCC received pembrolizumab 2 mg/kg every 3 weeks for ≤2 years. Patients were followed for a median of 31.8 months.ResultsOverall response rate to pembrolizumab was 58% (complete response 30%+partial response 28%; 95% CI 43.2 to 71.8). Among 29 responders, the median response duration was not reached (NR) at 3 years (range 1.0+ to 51.8+ months). Median progression-free survival (PFS) was 16.8 months (95% CI 4.6 to 43.4) and the 3-year PFS was 39.1%. Median OS was NR; the 3-year OS was 59.4% for all patients and 89.5% for responders. Baseline Eastern Cooperative Oncology Group performance status of 0, greater per cent tumor reduction, completion of 2 years of treatment and low neutrophil-to-lymphocyte ratio were associated with response and longer survival. Among patients with initial disease progression or those who developed progression after response or stable disease, some had extended survival with subsequent treatments including chemotherapies and immunotherapies.ConclusionsThis study represents the longest available follow-up from any first-line anti-programmed death-(ligand) 1 (anti-PD-(L)1) therapy in MCC, confirming durable PFS and OS in a proportion of patients. After initial tumor progression or relapse following response, some patients receiving salvage therapies survived. Improving the management of anti-PD-(L)1-refractory MCC remains a challenge and a high priority.Trial registration numberNCT02267603.

Sign in / Sign up

Export Citation Format

Share Document