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

Publication ,  Journal Article
Nghiem, P; Bhatia, S; Lipson, EJ; Sharfman, WH; Kudchadkar, RR; Brohl, AS; Friedlander, PA; Daud, A; Kluger, HM; Reddy, SA; Boulmay, BC ...
Published in: J Clin Oncol
March 20, 2019

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.

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Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 20, 2019

Volume

37

Issue

9

Start / End Page

693 / 702

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Response Evaluation Criteria in Solid Tumors
  • Remission Induction
  • Progression-Free Survival
  • Pneumonia
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Hypothyroidism
  • Humans
 

Citation

APA
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MLA
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Nghiem, P., Bhatia, S., Lipson, E. J., Sharfman, W. H., Kudchadkar, R. R., Brohl, A. S., … Topalian, S. L. (2019). Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol, 37(9), 693–702. https://doi.org/10.1200/JCO.18.01896
Nghiem, Paul, Shailender Bhatia, Evan J. Lipson, William H. Sharfman, Ragini R. Kudchadkar, Andrew S. Brohl, Phillip A. Friedlander, et al. “Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.J Clin Oncol 37, no. 9 (March 20, 2019): 693–702. https://doi.org/10.1200/JCO.18.01896.
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, et al. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693–702.
Nghiem, Paul, et al. “Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy.J Clin Oncol, vol. 37, no. 9, Mar. 2019, pp. 693–702. Pubmed, doi:10.1200/JCO.18.01896.
Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693–702.

Published In

J Clin Oncol

DOI

EISSN

1527-7755

Publication Date

March 20, 2019

Volume

37

Issue

9

Start / End Page

693 / 702

Location

United States

Related Subject Headings

  • Skin Neoplasms
  • Response Evaluation Criteria in Solid Tumors
  • Remission Induction
  • Progression-Free Survival
  • Pneumonia
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Hypothyroidism
  • Humans