Your browser doesn't support javascript.
loading
Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial.
Shitara, Kohei; Özgüroglu, Mustafa; Bang, Yung-Jue; Di Bartolomeo, Maria; Mandalà, Mario; Ryu, Min-Hee; Fornaro, Lorenzo; Olesinski, Tomasz; Caglevic, Christian; Chung, Hyun C; Muro, Kei; Goekkurt, Eray; Mansoor, Wasat; McDermott, Raymond S; Shacham-Shmueli, Einat; Chen, Xinqun; Mayo, Carlos; Kang, S Peter; Ohtsu, Atsushi; Fuchs, Charles S.
Afiliación
  • Shitara K; National Cancer Center Hospital East, Kashiwa, Japan. Electronic address: kshitara@east.ncc.go.jp.
  • Özgüroglu M; Istanbul University, Cerrahpasa School of Medicine, Istanbul, Turkey.
  • Bang YJ; Seoul National University College of Medicine, Seoul, South Korea.
  • Di Bartolomeo M; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
  • Mandalà M; Papa Giovanni XXIII Hospital, Bergamo, Italy.
  • Ryu MH; University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
  • Fornaro L; Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
  • Olesinski T; Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland.
  • Caglevic C; Fundación Arturo López Pérez - Clínica Alemana de Santiago, Santiago, Chile.
  • Chung HC; Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
  • Muro K; Aichi Cancer Center Hospital, Nagoya, Japan.
  • Goekkurt E; Hematology Oncology Practice Eppendorf (HOPE), Hamburg, Germany; University Cancer Center Hamburg, Hamburg, Germany.
  • Mansoor W; Christie Hospital NHS Foundation Trust, Manchester, UK.
  • McDermott RS; Adelaide and Meath Hospital, Dublin, Ireland.
  • Shacham-Shmueli E; Sheba Medical Center, Ramat Gan, Israel.
  • Chen X; Merck & Co, Kenilworth, NJ, USA.
  • Mayo C; Merck & Co, Kenilworth, NJ, USA.
  • Kang SP; Merck & Co, Kenilworth, NJ, USA.
  • Ohtsu A; National Cancer Center Hospital East, Kashiwa, Japan.
  • Fuchs CS; Yale Cancer Center, Smilow Cancer Hospital, New Haven, CT, USA.
Lancet ; 392(10142): 123-133, 2018 07 14.
Article en En | MEDLINE | ID: mdl-29880231
ABSTRACT

BACKGROUND:

Patients with advanced gastric or gastro-oesophageal junction cancer that progresses on chemotherapy have poor outcomes. We compared pembrolizumab with paclitaxel in patients with advanced gastric or gastro-oesophageal junction cancer that progressed on first-line chemotherapy with a platinum and fluoropyrimidine.

METHODS:

This randomised, open-label, phase 3 study was done at 148 medical centres in 30 countries. Eligible patients were randomised (11) in blocks of four per stratum with an interactive voice-response and integrated web-response system to receive either pembrolizumab 200 mg every 3 weeks for up to 2 years or standard-dose paclitaxel. Primary endpoints were overall survival and progression-free survival in patients with a programmed cell death ligand 1 (PD-L1) combined positive score (CPS) of 1 or higher. Safety was assessed in all patients, irrespective of CPS. The significance threshold for overall survival was p=0·0135 (one-sided). This trial is registered at ClinicalTrials.gov, number NCT02370498.

FINDINGS:

Between June 4, 2015, and July 26, 2016, 592 patients were enrolled. Of the 395 patients who had a PD-L1 CPS of 1 or higher, 196 patients were assigned to receive pembrolizumab and 199 patients were assigned to receive paclitaxel. As of Oct 26, 2017, 326 patients in the population with CPS of 1 or higher had died (151 [77%] of 196 patients in the pembrolizumab group and 175 [88%] of 199 patients in the paclitaxel group). Median overall survival was 9·1 months (95% CI 6·2-10·7) with pembrolizumab and 8·3 months (7·6-9·0) with paclitaxel (hazard ratio [HR] 0·82, 95% CI 0·66-1·03; one-sided p=0·0421). Median progression-free survival was 1·5 months (95% CI 1·4-2·0) with pembrolizumab and 4·1 months (3·1-4·2) with paclitaxel (HR 1·27, 95% CI 1·03-1·57). In the total population, grade 3-5 treatment-related adverse events occurred in 42 (14%) of the 294 patients treated with pembrolizumab and 96 (35%) of the 276 patients treated with paclitaxel.

INTERPRETATION:

Pembrolizumab did not significantly improve overall survival compared with paclitaxel as second-line therapy for advanced gastric or gastro-oesophageal junction cancer with PD-L1 CPS of 1 or higher. Pembrolizumab had a better safety profile than paclitaxel. Additional trials of pembrolizumab in gastric and gastro-oesophageal cancer are ongoing.

FUNDING:

Merck Sharp & Dohme, a subsidiary of Merck & Co.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Neoplasias Esofágicas / Adenocarcinoma / Paclitaxel / Unión Esofagogástrica / Anticuerpos Monoclonales Humanizados Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Lancet Año: 2018 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Gástricas / Neoplasias Esofágicas / Adenocarcinoma / Paclitaxel / Unión Esofagogástrica / Anticuerpos Monoclonales Humanizados Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Lancet Año: 2018 Tipo del documento: Article