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

Paul Nghiem, Shailender Bhatia, Evan Lipson, William Sharfman, Ragini R. Kudchadkar, Andrew S. Brohl, Phillip A. Friedlander, Adil Daud, Harriet M. Kluger, Sunil A. Reddy, Brian C. Boulmay, Adam I. Riker, Melissa A. Burgess, Brent A. Hanks, Thomas Olencki, Kim Margolin, Lisa M. Lundgren, Abha Soni, Nirasha Ramchurren, Candice Church & 11 others Song Y. Park, Michi M. Shinohara, Bob Salim, Janis M Taube, Steven R. Bird, Nageatte Ibrahim, Steven P. Fling, Blanca Homet Moreno, Elad Sharon, Martin A. Cheever, Suzanne Topalian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)693-702
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number9
DOIs
StatePublished - Mar 20 2019

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Merkel Cell Carcinoma
Disease-Free Survival
Survival
Neoplasms
Merkel cell polyomavirus
Cell Death
Therapeutics
Survival Rate
Drug Therapy
Oncogenic Viruses
Skin Neoplasms
Immunotherapy
pembrolizumab
Observation
Clinical Trials
Ligands
Viruses
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. / Nghiem, Paul; Bhatia, Shailender; Lipson, Evan; Sharfman, William; Kudchadkar, Ragini R.; Brohl, Andrew S.; Friedlander, Phillip A.; Daud, Adil; Kluger, Harriet M.; Reddy, Sunil A.; Boulmay, Brian C.; Riker, Adam I.; Burgess, Melissa A.; Hanks, Brent A.; Olencki, Thomas; Margolin, Kim; Lundgren, Lisa M.; Soni, Abha; Ramchurren, Nirasha; Church, Candice; Park, Song Y.; Shinohara, Michi M.; Salim, Bob; Taube, Janis M; Bird, Steven R.; Ibrahim, Nageatte; Fling, Steven P.; Moreno, Blanca Homet; Sharon, Elad; Cheever, Martin A.; Topalian, Suzanne.

In: Journal of Clinical Oncology, Vol. 37, No. 9, 20.03.2019, p. 693-702.

Research output: Contribution to journalArticle

Nghiem, P, Bhatia, S, Lipson, E, Sharfman, W, 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, Moreno, BH, Sharon, E, Cheever, MA & Topalian, S 2019, 'Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy', Journal of Clinical Oncology, vol. 37, no. 9, pp. 693-702. https://doi.org/10.1200/JCO.18.01896
Nghiem, Paul ; Bhatia, Shailender ; Lipson, Evan ; Sharfman, William ; Kudchadkar, Ragini R. ; Brohl, Andrew S. ; Friedlander, Phillip A. ; Daud, Adil ; Kluger, Harriet M. ; Reddy, Sunil A. ; Boulmay, Brian C. ; Riker, Adam I. ; Burgess, Melissa A. ; Hanks, Brent A. ; Olencki, Thomas ; Margolin, Kim ; Lundgren, Lisa M. ; Soni, Abha ; Ramchurren, Nirasha ; Church, Candice ; Park, Song Y. ; Shinohara, Michi M. ; Salim, Bob ; Taube, Janis M ; Bird, Steven R. ; Ibrahim, Nageatte ; Fling, Steven P. ; Moreno, Blanca Homet ; Sharon, Elad ; Cheever, Martin A. ; Topalian, Suzanne. / Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 9. pp. 693-702.
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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 na{\"i}ve 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.",
author = "Paul Nghiem and Shailender Bhatia and Evan Lipson and William Sharfman and Kudchadkar, {Ragini R.} and Brohl, {Andrew S.} and Friedlander, {Phillip A.} and Adil Daud and Kluger, {Harriet M.} and Reddy, {Sunil A.} and Boulmay, {Brian C.} and Riker, {Adam I.} and Burgess, {Melissa A.} and Hanks, {Brent A.} and Thomas Olencki and Kim Margolin and Lundgren, {Lisa M.} and Abha Soni and Nirasha Ramchurren and Candice Church and Park, {Song Y.} and Shinohara, {Michi M.} and Bob Salim and Taube, {Janis M} and Bird, {Steven R.} and Nageatte Ibrahim and Fling, {Steven P.} and Moreno, {Blanca Homet} and Elad Sharon and Cheever, {Martin A.} and Suzanne Topalian",
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TY - JOUR

T1 - Durable tumor regression and overall survival in patients with advanced Merkel cell carcinoma receiving pembrolizumab as first-line therapy

AU - Nghiem, Paul

AU - Bhatia, Shailender

AU - Lipson, Evan

AU - Sharfman, William

AU - Kudchadkar, Ragini R.

AU - Brohl, Andrew S.

AU - Friedlander, Phillip A.

AU - Daud, Adil

AU - Kluger, Harriet M.

AU - Reddy, Sunil A.

AU - Boulmay, Brian C.

AU - Riker, Adam I.

AU - Burgess, Melissa A.

AU - Hanks, Brent A.

AU - Olencki, Thomas

AU - Margolin, Kim

AU - Lundgren, Lisa M.

AU - Soni, Abha

AU - Ramchurren, Nirasha

AU - Church, Candice

AU - Park, Song Y.

AU - Shinohara, Michi M.

AU - Salim, Bob

AU - Taube, Janis M

AU - Bird, Steven R.

AU - Ibrahim, Nageatte

AU - Fling, Steven P.

AU - Moreno, Blanca Homet

AU - Sharon, Elad

AU - Cheever, Martin A.

AU - Topalian, Suzanne

PY - 2019/3/20

Y1 - 2019/3/20

N2 - 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.

AB - 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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