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Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial

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Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. / Shitara, Kohei; Van Cutsem, Eric; Bang, Yung-Jue; Fuchs, Charles; Wyrwicz, Lucjan; Lee, Keun-Wook; Kudaba, Iveta; Garrido, Marcelo; Chung, Hyun Cheol; Lee, Jeeyun; Castro, Hugo Raul; Mansoor, Wasat; Braghiroli, Maria Ignez; Karaseva, Nina; Caglevic, Christian; Villanueva, Luis; Goekkurt, Eray; Satake, Hironaga; Enzinger, Peter; Alsina, Maria; Benson, Al; Chao, Joseph; Ko, Andrew H; Wainberg, Zev A; Kher, Uma; Shah, Sukrut; Kang, S Peter; Tabernero, Josep.

In: JAMA ONCOL, Vol. 6, No. 10, 01.10.2020, p. 1571-1580.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Shitara, K, Van Cutsem, E, Bang, Y-J, Fuchs, C, Wyrwicz, L, Lee, K-W, Kudaba, I, Garrido, M, Chung, HC, Lee, J, Castro, HR, Mansoor, W, Braghiroli, MI, Karaseva, N, Caglevic, C, Villanueva, L, Goekkurt, E, Satake, H, Enzinger, P, Alsina, M, Benson, A, Chao, J, Ko, AH, Wainberg, ZA, Kher, U, Shah, S, Kang, SP & Tabernero, J 2020, 'Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial', JAMA ONCOL, vol. 6, no. 10, pp. 1571-1580. https://doi.org/10.1001/jamaoncol.2020.3370

APA

Shitara, K., Van Cutsem, E., Bang, Y-J., Fuchs, C., Wyrwicz, L., Lee, K-W., Kudaba, I., Garrido, M., Chung, H. C., Lee, J., Castro, H. R., Mansoor, W., Braghiroli, M. I., Karaseva, N., Caglevic, C., Villanueva, L., Goekkurt, E., Satake, H., Enzinger, P., ... Tabernero, J. (2020). Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA ONCOL, 6(10), 1571-1580. https://doi.org/10.1001/jamaoncol.2020.3370

Vancouver

Shitara K, Van Cutsem E, Bang Y-J, Fuchs C, Wyrwicz L, Lee K-W et al. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA ONCOL. 2020 Oct 1;6(10):1571-1580. https://doi.org/10.1001/jamaoncol.2020.3370

Bibtex

@article{6618b3a64ba04832adb45ae1af6dc0a9,
title = "Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial",
abstract = "Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater.Design, Setting, and Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.Interventions: Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks.Main Outcomes and Measures: Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater.Results: A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02; P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively.Conclusions and Relevance: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.Trial Registration: ClinicalTrials.gov Identifier: NCT02494583.",
author = "Kohei Shitara and {Van Cutsem}, Eric and Yung-Jue Bang and Charles Fuchs and Lucjan Wyrwicz and Keun-Wook Lee and Iveta Kudaba and Marcelo Garrido and Chung, {Hyun Cheol} and Jeeyun Lee and Castro, {Hugo Raul} and Wasat Mansoor and Braghiroli, {Maria Ignez} and Nina Karaseva and Christian Caglevic and Luis Villanueva and Eray Goekkurt and Hironaga Satake and Peter Enzinger and Maria Alsina and Al Benson and Joseph Chao and Ko, {Andrew H} and Wainberg, {Zev A} and Uma Kher and Sukrut Shah and Kang, {S Peter} and Josep Tabernero",
year = "2020",
month = oct,
day = "1",
doi = "10.1001/jamaoncol.2020.3370",
language = "English",
volume = "6",
pages = "1571--1580",
journal = "JAMA ONCOL",
issn = "2374-2437",
publisher = "American Medical Association",
number = "10",

}

RIS

TY - JOUR

T1 - Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial

AU - Shitara, Kohei

AU - Van Cutsem, Eric

AU - Bang, Yung-Jue

AU - Fuchs, Charles

AU - Wyrwicz, Lucjan

AU - Lee, Keun-Wook

AU - Kudaba, Iveta

AU - Garrido, Marcelo

AU - Chung, Hyun Cheol

AU - Lee, Jeeyun

AU - Castro, Hugo Raul

AU - Mansoor, Wasat

AU - Braghiroli, Maria Ignez

AU - Karaseva, Nina

AU - Caglevic, Christian

AU - Villanueva, Luis

AU - Goekkurt, Eray

AU - Satake, Hironaga

AU - Enzinger, Peter

AU - Alsina, Maria

AU - Benson, Al

AU - Chao, Joseph

AU - Ko, Andrew H

AU - Wainberg, Zev A

AU - Kher, Uma

AU - Shah, Sukrut

AU - Kang, S Peter

AU - Tabernero, Josep

PY - 2020/10/1

Y1 - 2020/10/1

N2 - Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater.Design, Setting, and Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.Interventions: Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks.Main Outcomes and Measures: Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater.Results: A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02; P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively.Conclusions and Relevance: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.Trial Registration: ClinicalTrials.gov Identifier: NCT02494583.

AB - Importance: Safe and effective therapies for untreated, advanced gastric/gastroesophageal junction (G/GEJ) cancer remain an unmet need.Objective: To evaluate the antitumor activity of pembrolizumab, pembrolizumab plus chemotherapy, or chemotherapy alone in patients with untreated, advanced G/GEJ cancer with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or greater.Design, Setting, and Participants: The phase 3 KEYNOTE-062 randomized, controlled, partially blinded interventional trial enrolled 763 patients with untreated, locally advanced/unresectable or metastatic G/GEJ cancer with PD-L1 CPS of 1 or greater from 200 centers in 29 countries between September 18, 2015, and May 26, 2017.Interventions: Patients were randomized 1:1:1 to pembrolizumab 200 mg, pembrolizumab plus chemotherapy (cisplatin 80 mg/m2/d on day 1 plus fluorouracil 800 mg/m2/d on days 1 to 5 or capecitabine 1000 mg/m2 twice daily), or chemotherapy plus placebo, every 3 weeks.Main Outcomes and Measures: Primary end points were overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 CPS of 1 or greater or 10 or greater.Results: A total of 763 patients were randomized to pembrolizumab (n = 256), pembrolizumab plus chemotherapy (n = 257), or chemotherapy (n = 250). The median (range) age of all patients in the study cohort was 62 (20-87) years; 554 of 763 (72.6%) were men. At final analysis, after a median (range) follow-up of 29.4 (22.0-41.3) months, pembrolizumab was noninferior to chemotherapy for OS in patients with CPS of 1 or greater (median, 10.6 vs 11.1 months; hazard ratio [HR], 0.91; 99.2% CI, 0.69-1.18). Pembrolizumab monotherapy was not superior to chemotherapy in patients with CPS of 1 or greater. Pembrolizumab prolonged OS vs chemotherapy in patients with CPS of 10 or greater (median, 17.4 vs 10.8 months; HR, 0.69; 95% CI, 0.49-0.97), but this difference was not statistically tested. Pembrolizumab plus chemotherapy was not superior to chemotherapy for OS in patients with CPS of 1 or greater (12.5 vs 11.1 months; HR, 0.85; 95% CI, 0.70-1.03; P = .05) or CPS of 10 or greater (12.3 vs 10.8 months; HR, 0.85; 95% CI, 0.62-1.17; P = .16) or for PFS in patients with CPS of 1 or greater (6.9 vs 6.4 months; HR, 0.84; 95% CI, 0.70-1.02; P = .04). Grade 3 to 5 treatment-related adverse event rates for pembrolizumab, pembrolizumab plus chemotherapy, and chemotherapy were 17%, 73%, and 69%, respectively.Conclusions and Relevance: This phase 3 randomized clinical trial found that among patients with untreated, advanced G/GEJ cancer, pembrolizumab was noninferior to chemotherapy, with fewer adverse events observed. Pembrolizumab or pembrolizumab plus chemotherapy was not superior to chemotherapy for the OS and PFS end points tested.Trial Registration: ClinicalTrials.gov Identifier: NCT02494583.

U2 - 10.1001/jamaoncol.2020.3370

DO - 10.1001/jamaoncol.2020.3370

M3 - SCORING: Journal article

C2 - 32880601

VL - 6

SP - 1571

EP - 1580

JO - JAMA ONCOL

JF - JAMA ONCOL

SN - 2374-2437

IS - 10

ER -