Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial

Charles S. Fuchs, Toshihiko Doi, Raymond W. Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia Jalal, Manish A. Shah, Jean Phillipe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V. Catenacci, Atsushi Ohtsu, Kohei Shitara, Ravit Geva, Jonathan Bleeker, Andrew H. KoGeoffrey Ku, Philip Philip, Peter C. Enzinger, Yung Jue Bang, Diane Levitan, Jiangdian Wang, Minori Rosales, Rita P. Dalal, Harry H. Yoon

Research output: Contribution to journalArticle

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Abstract

IMPORTANCE Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. OBJECTIVE To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. DESIGN, SETTING, AND PARTICIPANTS In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. INTERVENTION Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)–positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. RESULTS Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1–positive and PD-L1–negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. CONCLUSIONS AND RELEVANCE Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted.

Original languageEnglish (US)
Article number2675013
JournalJAMA oncology
Volume4
Issue number5
DOIs
StatePublished - May 1 2018

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Esophagogastric Junction
Stomach
Safety
Neoplasms
CD274 Antigen
pembrolizumab
Therapeutics
Poisons

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer : Phase 2 clinical KEYNOTE-059 trial. / Fuchs, Charles S.; Doi, Toshihiko; Jang, Raymond W.; Muro, Kei; Satoh, Taroh; Machado, Manuela; Sun, Weijing; Jalal, Shadia; Shah, Manish A.; Metges, Jean Phillipe; Garrido, Marcelo; Golan, Talia; Mandala, Mario; Wainberg, Zev A.; Catenacci, Daniel V.; Ohtsu, Atsushi; Shitara, Kohei; Geva, Ravit; Bleeker, Jonathan; Ko, Andrew H.; Ku, Geoffrey; Philip, Philip; Enzinger, Peter C.; Bang, Yung Jue; Levitan, Diane; Wang, Jiangdian; Rosales, Minori; Dalal, Rita P.; Yoon, Harry H.

In: JAMA oncology, Vol. 4, No. 5, 2675013, 01.05.2018.

Research output: Contribution to journalArticle

Fuchs, CS, Doi, T, Jang, RW, Muro, K, Satoh, T, Machado, M, Sun, W, Jalal, S, Shah, MA, Metges, JP, Garrido, M, Golan, T, Mandala, M, Wainberg, ZA, Catenacci, DV, Ohtsu, A, Shitara, K, Geva, R, Bleeker, J, Ko, AH, Ku, G, Philip, P, Enzinger, PC, Bang, YJ, Levitan, D, Wang, J, Rosales, M, Dalal, RP & Yoon, HH 2018, 'Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial', JAMA oncology, vol. 4, no. 5, 2675013. https://doi.org/10.1001/jamaoncol.2018.0013
Fuchs, Charles S. ; Doi, Toshihiko ; Jang, Raymond W. ; Muro, Kei ; Satoh, Taroh ; Machado, Manuela ; Sun, Weijing ; Jalal, Shadia ; Shah, Manish A. ; Metges, Jean Phillipe ; Garrido, Marcelo ; Golan, Talia ; Mandala, Mario ; Wainberg, Zev A. ; Catenacci, Daniel V. ; Ohtsu, Atsushi ; Shitara, Kohei ; Geva, Ravit ; Bleeker, Jonathan ; Ko, Andrew H. ; Ku, Geoffrey ; Philip, Philip ; Enzinger, Peter C. ; Bang, Yung Jue ; Levitan, Diane ; Wang, Jiangdian ; Rosales, Minori ; Dalal, Rita P. ; Yoon, Harry H. / Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer : Phase 2 clinical KEYNOTE-059 trial. In: JAMA oncology. 2018 ; Vol. 4, No. 5.
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title = "Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: Phase 2 clinical KEYNOTE-059 trial",
abstract = "IMPORTANCE Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. OBJECTIVE To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. DESIGN, SETTING, AND PARTICIPANTS In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. INTERVENTION Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)–positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. RESULTS Of 259 patients enrolled, most were male (198 [76.4{\%}]) and white (200 [77.2{\%}]); median (range) age was 62 (24-89) years. Objective response rate was 11.6{\%} (95{\%} CI, 8.0{\%}-16.1{\%}; 30 of 259 patients), with complete response in 2.3{\%} (95{\%} CI, 0.9{\%}-5.0{\%}; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5{\%} (95{\%} CI, 10.1{\%}-22.4{\%}; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4{\%} (95{\%} CI, 2.6{\%}-12.8{\%}; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1–positive and PD-L1–negative tumors, respectively. Forty-six patients (17.8{\%}) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8{\%}) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. CONCLUSIONS AND RELEVANCE Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted.",
author = "Fuchs, {Charles S.} and Toshihiko Doi and Jang, {Raymond W.} and Kei Muro and Taroh Satoh and Manuela Machado and Weijing Sun and Shadia Jalal and Shah, {Manish A.} and Metges, {Jean Phillipe} and Marcelo Garrido and Talia Golan and Mario Mandala and Wainberg, {Zev A.} and Catenacci, {Daniel V.} and Atsushi Ohtsu and Kohei Shitara and Ravit Geva and Jonathan Bleeker and Ko, {Andrew H.} and Geoffrey Ku and Philip Philip and Enzinger, {Peter C.} and Bang, {Yung Jue} and Diane Levitan and Jiangdian Wang and Minori Rosales and Dalal, {Rita P.} and Yoon, {Harry H.}",
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month = "5",
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TY - JOUR

T1 - Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer

T2 - Phase 2 clinical KEYNOTE-059 trial

AU - Fuchs, Charles S.

AU - Doi, Toshihiko

AU - Jang, Raymond W.

AU - Muro, Kei

AU - Satoh, Taroh

AU - Machado, Manuela

AU - Sun, Weijing

AU - Jalal, Shadia

AU - Shah, Manish A.

AU - Metges, Jean Phillipe

AU - Garrido, Marcelo

AU - Golan, Talia

AU - Mandala, Mario

AU - Wainberg, Zev A.

AU - Catenacci, Daniel V.

AU - Ohtsu, Atsushi

AU - Shitara, Kohei

AU - Geva, Ravit

AU - Bleeker, Jonathan

AU - Ko, Andrew H.

AU - Ku, Geoffrey

AU - Philip, Philip

AU - Enzinger, Peter C.

AU - Bang, Yung Jue

AU - Levitan, Diane

AU - Wang, Jiangdian

AU - Rosales, Minori

AU - Dalal, Rita P.

AU - Yoon, Harry H.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - IMPORTANCE Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. OBJECTIVE To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. DESIGN, SETTING, AND PARTICIPANTS In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. INTERVENTION Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)–positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. RESULTS Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1–positive and PD-L1–negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. CONCLUSIONS AND RELEVANCE Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted.

AB - IMPORTANCE Therapeutic options are needed for patients with advanced gastric cancer whose disease has progressed after 2 or more lines of therapy. OBJECTIVE To evaluate the safety and efficacy of pembrolizumab in a cohort of patients with previously treated gastric or gastroesophageal junction cancer. DESIGN, SETTING, AND PARTICIPANTS In the phase 2, global, open-label, single-arm, multicohort KEYNOTE-059 study, 259 patients in 16 countries were enrolled in a cohort between March 2, 2015, and May 26, 2016. Median (range) follow-up was 5.8 (0.5-21.6) months. INTERVENTION Patients received pembrolizumab, 200 mg, intravenously every 3 weeks until disease progression, investigator or patient decision to withdraw, or unacceptable toxic effects. MAIN OUTCOMES AND MEASURES Primary end points were objective response rate and safety. Objective response rate was assessed by central radiologic review per Response Evaluation Criteria in Solid Tumors, version 1.1, in all patients and those with programmed cell death 1 ligand 1 (PD-L1)–positive tumors. Expression of PD-L1 was assessed by immunohistochemistry. Secondary end points included response duration. RESULTS Of 259 patients enrolled, most were male (198 [76.4%]) and white (200 [77.2%]); median (range) age was 62 (24-89) years. Objective response rate was 11.6% (95% CI, 8.0%-16.1%; 30 of 259 patients), with complete response in 2.3% (95% CI, 0.9%-5.0%; 6 of 259 patients). Median (range) response duration was 8.4 (1.6+ to 17.3+) months (+ indicates that patients had no progressive disease at their last assessment). Objective response rate and median (range) response duration were 15.5% (95% CI, 10.1%-22.4%; 23 of 148 patients) and 16.3 (1.6+ to 17.3+) months and 6.4% (95% CI, 2.6%-12.8%; 7 of 109 patients) and 6.9 (2.4 to 7.0+) months in patients with PD-L1–positive and PD-L1–negative tumors, respectively. Forty-six patients (17.8%) experienced 1 or more grade 3 to 5 treatment-related adverse events. Two patients (0.8%) discontinued because of treatment-related adverse events, and 2 deaths were considered related to treatment. CONCLUSIONS AND RELEVANCE Pembrolizumab monotherapy demonstrated promising activity and manageable safety in patients with advanced gastric or gastroesophageal junction cancer who had previously received at least 2 lines of treatment. Durable responses were observed in patients with PD-L1–positive and PD-L1–negative tumors. Further study of pembrolizumab for this group of patients is warranted.

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