Format

Send to

Choose Destination
J Clin Oncol. 2019 Feb 6:JCO1801896. doi: 10.1200/JCO.18.01896. [Epub ahead of print]

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

Author information

1
1 University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA.
2
2 Johns Hopkins Kimmel Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy, Baltimore, MD.
3
3 Emory University, Atlanta, GA.
4
4 Moffitt Cancer Center, Tampa, FL.
5
5 Mount Sinai Medical Center, New York, NY.
6
6 University of California San Francisco, San Francisco, CA.
7
7 Yale University, New Haven, CT.
8
8 Stanford University, Stanford, CA.
9
9 Louisiana State University, New Orleans, LA.
10
10 University of Pittsburgh, Pittsburgh, PA.
11
11 Duke University Medical Center, Durham, NC.
12
12 Ohio State University Comprehensive Cancer Center, Columbus, OH.
13
13 City of Hope, Duarte, CA.
14
14 Fred Hutchinson Cancer Research Center/Cancer Immunotherapy Trials Network, Seattle, WA.
15
15 University of Washington, Seattle, WA.
16
16 Axio Research, Seattle, WA.
17
17 Merck Research Laboratories, Kenilworth, NJ.
18
18 National Cancer Institute, Cancer Therapy Evaluation Program, Bethesda, MD.

Abstract

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.

PMID:
30726175
DOI:
10.1200/JCO.18.01896

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center