Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study

Yung Jue Bang, Yoon Koo Kang, Daniel V. Catenacci, Kei Muro, Charles S. Fuchs, Ravit Geva, Hiroki Hara, Talia Golan, Marcelo Garrido, Shadia Jalal, Christophe Borg, Toshihiko Doi, Harry H. Yoon, Mary J. Savage, Jiangdian Wang, Rita P. Dalal, Sukrut Shah, Zev A. Wainberg, Hyun Cheol Chung

Research output: Contribution to journalArticle

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Abstract

Background: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. Methods: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m 2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m 2 on days 1–5 of each 3-week cycle (or capecitabine 1000 mg/m 2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). Results: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8–24.1) and 17.5 months (range 1.7–20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3–5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7–78.9] (combination therapy) and 25.8% (95% CI 11.9–44.6) (monotherapy). Conclusions: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. Clinical Trial: ClinicalTrials.gov NCT02335411.

Original languageEnglish (US)
JournalGastric Cancer
DOIs
StatePublished - Jan 1 2019

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Esophagogastric Junction
Combination Drug Therapy
Stomach
Adenocarcinoma
Therapeutics
Confidence Intervals
Safety
pembrolizumab
Death Domain Receptors
Fluorouracil
Cisplatin
Pneumonia
Japan
Clinical Trials
Drug Therapy

Keywords

  • 5-Fluorouracil
  • Capecitabine
  • Cisplatin
  • Gastric cancer
  • Pembrolizumab

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology
  • Cancer Research

Cite this

Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma : results from the phase II nonrandomized KEYNOTE-059 study. / Bang, Yung Jue; Kang, Yoon Koo; Catenacci, Daniel V.; Muro, Kei; Fuchs, Charles S.; Geva, Ravit; Hara, Hiroki; Golan, Talia; Garrido, Marcelo; Jalal, Shadia; Borg, Christophe; Doi, Toshihiko; Yoon, Harry H.; Savage, Mary J.; Wang, Jiangdian; Dalal, Rita P.; Shah, Sukrut; Wainberg, Zev A.; Chung, Hyun Cheol.

In: Gastric Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Bang, YJ, Kang, YK, Catenacci, DV, Muro, K, Fuchs, CS, Geva, R, Hara, H, Golan, T, Garrido, M, Jalal, S, Borg, C, Doi, T, Yoon, HH, Savage, MJ, Wang, J, Dalal, RP, Shah, S, Wainberg, ZA & Chung, HC 2019, 'Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma: results from the phase II nonrandomized KEYNOTE-059 study', Gastric Cancer. https://doi.org/10.1007/s10120-018-00909-5
Bang, Yung Jue ; Kang, Yoon Koo ; Catenacci, Daniel V. ; Muro, Kei ; Fuchs, Charles S. ; Geva, Ravit ; Hara, Hiroki ; Golan, Talia ; Garrido, Marcelo ; Jalal, Shadia ; Borg, Christophe ; Doi, Toshihiko ; Yoon, Harry H. ; Savage, Mary J. ; Wang, Jiangdian ; Dalal, Rita P. ; Shah, Sukrut ; Wainberg, Zev A. ; Chung, Hyun Cheol. / Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma : results from the phase II nonrandomized KEYNOTE-059 study. In: Gastric Cancer. 2019.
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abstract = "Background: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. Methods: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m 2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m 2 on days 1–5 of each 3-week cycle (or capecitabine 1000 mg/m 2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). Results: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8–24.1) and 17.5 months (range 1.7–20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0{\%}); none were fatal. In the monotherapy cohort, grade 3–5 treatment-related adverse events occurred in seven patients (22.6{\%}); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0{\%} [95{\%} confidence interval (CI), 38.7–78.9] (combination therapy) and 25.8{\%} (95{\%} CI 11.9–44.6) (monotherapy). Conclusions: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. Clinical Trial: ClinicalTrials.gov NCT02335411.",
keywords = "5-Fluorouracil, Capecitabine, Cisplatin, Gastric cancer, Pembrolizumab",
author = "Bang, {Yung Jue} and Kang, {Yoon Koo} and Catenacci, {Daniel V.} and Kei Muro and Fuchs, {Charles S.} and Ravit Geva and Hiroki Hara and Talia Golan and Marcelo Garrido and Shadia Jalal and Christophe Borg and Toshihiko Doi and Yoon, {Harry H.} and Savage, {Mary J.} and Jiangdian Wang and Dalal, {Rita P.} and Sukrut Shah and Wainberg, {Zev A.} and Chung, {Hyun Cheol}",
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TY - JOUR

T1 - Pembrolizumab alone or in combination with chemotherapy as first-line therapy for patients with advanced gastric or gastroesophageal junction adenocarcinoma

T2 - results from the phase II nonrandomized KEYNOTE-059 study

AU - Bang, Yung Jue

AU - Kang, Yoon Koo

AU - Catenacci, Daniel V.

AU - Muro, Kei

AU - Fuchs, Charles S.

AU - Geva, Ravit

AU - Hara, Hiroki

AU - Golan, Talia

AU - Garrido, Marcelo

AU - Jalal, Shadia

AU - Borg, Christophe

AU - Doi, Toshihiko

AU - Yoon, Harry H.

AU - Savage, Mary J.

AU - Wang, Jiangdian

AU - Dalal, Rita P.

AU - Shah, Sukrut

AU - Wainberg, Zev A.

AU - Chung, Hyun Cheol

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. Methods: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m 2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m 2 on days 1–5 of each 3-week cycle (or capecitabine 1000 mg/m 2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). Results: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8–24.1) and 17.5 months (range 1.7–20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3–5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7–78.9] (combination therapy) and 25.8% (95% CI 11.9–44.6) (monotherapy). Conclusions: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. Clinical Trial: ClinicalTrials.gov NCT02335411.

AB - Background: The multicohort, phase II, nonrandomized KEYNOTE-059 study evaluated pembrolizumab ± chemotherapy in advanced gastric/gastroesophageal junction cancer. Results from cohorts 2 and 3, evaluating first-line therapy, are presented. Methods: Patients ≥ 18 years old had previously untreated recurrent or metastatic gastric/gastroesophageal junction adenocarcinoma. Cohort 3 (monotherapy) had programmed death receptor 1 combined positive score ≥ 1. Cohort 2 (combination therapy) received pembrolizumab 200 mg on day 1, cisplatin 80 mg/m 2 on day 1 (up to 6 cycles), and 5-fluorouracil 800 mg/m 2 on days 1–5 of each 3-week cycle (or capecitabine 1000 mg/m 2 twice daily in Japan). Primary end points were safety (combination therapy) and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 by central review, and safety (monotherapy). Results: In the combination therapy and monotherapy cohorts, 25 and 31 patients were enrolled; median follow-up was 13.8 months (range 1.8–24.1) and 17.5 months (range 1.7–20.7), respectively. In the combination therapy cohort, grade 3/4 treatment-related adverse events occurred in 19 patients (76.0%); none were fatal. In the monotherapy cohort, grade 3–5 treatment-related adverse events occurred in seven patients (22.6%); one death was attributed to a treatment-related adverse event (pneumonitis). The objective response rate was 60.0% [95% confidence interval (CI), 38.7–78.9] (combination therapy) and 25.8% (95% CI 11.9–44.6) (monotherapy). Conclusions: Pembrolizumab demonstrated antitumor activity and was well tolerated as monotherapy and in combination with chemotherapy in patients with previously untreated advanced gastric/gastroesophageal junction adenocarcinoma. Clinical Trial: ClinicalTrials.gov NCT02335411.

KW - 5-Fluorouracil

KW - Capecitabine

KW - Cisplatin

KW - Gastric cancer

KW - Pembrolizumab

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U2 - 10.1007/s10120-018-00909-5

DO - 10.1007/s10120-018-00909-5

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