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ESMO 2017: Pembrolizumab Demonstrates Antitumour Activity in Advanced Gastric Cancer as Monotherapy and Combined with Chemotherapy

Update of KEYNOTE-059 study
08 Sep 2017
Cytotoxic Therapy
Gastrointestinal Cancers

Pembrolizumab continues to demonstrate promising clinical activity in patients with advanced gastric or gastroesophageal junction (GEJ) cancer, according to updated findings from the KEYNOTE-059 study presented during the ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.

Previously reported results from the global, phase II KEYNOTE-059 study (NCT02335411) showed manageable safety and promising antitumour activity both for single agent pembrolizumab and for pembrolizumab plus chemotherapy in patients with gastric or GEJ cancer.

The latest update of KEYNOTE-059 was presented at ESMO 2017 by Zev A. Wainberg, Medicine Hematology and Oncology, David Geffen School of Medicine at UCLA in Los Angeles, USA.

In the KEYNOTE-059 trial, patients with recurrent or metastatic gastric/GEJ adenocarcinoma were enrolled into 3 cohorts; 259 and 25 patients regardless of tumour PD-L1 expression were enroled into cohorts 1 and 2, respectively. Cohort 3 comprised 31 patients having confirmed PD-L1-positive tumours with a combined positive score of ≥1% per the PD-L1 immunohistochemistry 22C3 pharmDx assay.

All cohorts received pembrolizumab at 200 mg every 3 weeks for up to 2 years. Pembrolizumab was delivered following ≥2 prior lines of therapy in cohort 1, in combination with cisplatin plus 5-fluorouracil or capecitabine (in Japan only) as first-line in cohort 2, and as first-line monotherapy in cohort 3.   

Primary endpoints included safety in all 3 cohorts and objective response rate (ORR) per RECIST v1.1 by central review in cohorts 1 and 3. The key secondary endpoints were ORR in cohort 2 and duration of response (DoR) by RECIST v1.1, progression-free survival (PFS), and overall survival (OS).

The median follow-up in cohorts 1, 2, and 3 was 6 (range 2 to 25), 14 (range 2 to 24), and 18 (range 2 to 21) months, respectively.

The results 

The confirmed ORR with pembrolizumab in cohort 1 overall, which specifically had received 2 or more prior lines of therapy, was 12% (95% confidence interval 8, 17%); among PD-L1 positive patients the ORR rose to 16% (95% CI 11, 23), and the ORR was 6% (95% CI 3,13) in patients with PD-L1-negative tumours. The median PFS was 2.0 months (95% CI 2, 2) and median OS was 6 (95% CI 4, 7) months.


Best percentage change and longitudinal change in target lesion size.

© Zev Wainberg. 

Cohort 2, which received pembrolizumab in combination with chemotherapy, demonstrated confirmed ORR of 60% (95% CI 39, 79) overall; the ORR was 73% (95% CI 45, 92) in patients with PD-L1-positive versus 38% (95% CI 9, 76) in patients with PD-L1-negative tumours. Median PFS was 7 (95% CI 6, 11) months and median OS was 14 (95% CI 9, not estimable) months.


Best percentage change and longitudinal change in target lesion size.

© Zev Wainberg. 

Cohort 3 patients with PD-L1 expressing tumours receiving pembrolizumab as a first-line single agent had a confirmed ORR of 26% (95% CI 12, 45). Median PFS was 3 (95% CI 2, 6) months and median OS was not reached (95% CI 9, 21) months.


Best percentage change and longitudinal change in target lesion size.

© Zev Wainberg. 

The incidence of grades 3 to 5 treatment-related adverse events (TRAEs) in cohorts 1, 2 and 3, was 18%, 76%, and 23%, respectively. TRAEs led to discontinuation by 3% of cohort 1 patients and 12% of cohort 2 patients. TRAEs led to death in two cohort 1 and one cohort 3 patients.

FDA approval for pembrolizumab in gastric or GEJ adenocarcinoma awaited

A supplemental biologics license application based on data from the KEYNOTE-059 study was accepted by the US Food and Drug Administration (FDA) for a priority review in May 2017 for pembrolizumab as a treatment for patients following at least 2 lines of therapy for recurrent or advanced gastric or GEJ adenocarcinoma. The agency is expected to announce a decision by 22 September 2017.


According to the authors, these updated results demonstrated manageable safety and showed promising antitumour activity for pembrolizumab administered either alone or with chemotherapy in patients with advanced gastric/GEJ cancer.

Commenting on the study results, Prof. Eric Van Cutsem of the Digestive Oncology, Leuven, Belgium said that anti-PD antibodies will have a role in the management of advanced gastric adenocarcinoma, however role of PD-L1 expression has to clarified, predictive biomarkers have to be developed, role in early lines and in combination with chemotherapy has to be clarified and established, optimal combination and sequence have to be established as well.


This trial was sponsored by Merck & Co, Inc., Kenilworth, NJ, USA.


LBA28_PR – Wainberg ZA, et al. KEYNOTE-059 Update: Efficacy and Safety of Pembrolizumab Alone or in Combination With Chemotherapy in Patients With Advanced Gastric or Gastroesophageal (G/GEJ) cancer.

Last update: 08 Sep 2017

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