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KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer

Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, et al.

J Clin Oncol 35, 2017 (suppl; abstr 4003)

Editorial comment from Prof Lordick & Dr Smyth:
Keynote-059 confirms in a relatively big patient cohort, predominantly recruited in non-Asian populations, the efficacy of an anti-PD1-directed immune checkpoint therapy in advanced and pre-treated gastric cancer. Approximately every tenth patient responds to treatment. In case of a positive PD-L1-status (defined as ≥1% of cancer cells or tumor stroma cells stain positive for PD-L1) every fifth patient responds to Pembrolizumab. However, also PD-L1 negative cancers can respond. A very interesting response rate of 60% was seen in the relatively rare (4%) subgroup of patients with high microsatellite instability (MSI-H) gastric cancers.   The results of other ongoing clinical trials and decisions from regulatory authorities will determine in which lines of treatment and in which combination, if any pembrolizumab will be established in routinetreatment algorithms for gastric cancer. We hope that the authorities outside US will soon follow the good example of the FDA to register pembrolizumab for MSI-H irresectable and metastatic gastric cancer and other solid tumors.

ABSTRACT

Background:

Pembro has shown promising antitumor activity and manageable safety in a phase 1 study of pts with previously treated advanced gastric cancer. We conducted a global, multicohort, phase 2 study of pembro in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (KEYNOTE-059; NCT02335411).

Methods:

Cohort 1 enrolled 259 pts, aged $18 y with measurable recurrent or metastatic G/GEJ adenocarcinoma who had progressed on $2 prior chemotherapy regimens and had ECOG PS 0-1. Pts received pembro 200 mg Q3W up to 2 y or up to disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1+pts had expression in $1% tumor or stromal cells using IHC (22C3 antibody). Primary end points: ORR (RECIST 1.1, by central review), safety, and tolerability.

Results:

Of 259 pts in cohort 1, 76.4% were men; median age was 62.0 y. 51.7% and 48.3% received pembro as 3rd-line (3L) and 4L+ therapy, respectively. 57.1% had PD-L1+ tumors. At data cutoff (Oct 19, 2016), median duration of follow-up was 5.4 mo (range, 0.5 to 18.7). Overall ORR (CR + PR) was 11.2% (95% CI, 7.6-15.7); 1.9%of pts (95% CI, 0.6-4.4) had CR, 9.3% had PR (95% CI, 6.0-13.5), 17% (95% CI, 12.6-22.1) had SD, and 55.6% (95% CI, 49.3-61.7) had PD. Median DOR was 8.1 mo (range, 1.4+ to 15.1+). ORR was 14.9% (95% CI, 9.4-22.1) in 3L pts and 7.2% (95% CI, 3.3-13.2) in 4L+. In PD-L1+ pts, ORR was 15.5% (95% CI, 10.1-22.4) with 2.0% (95% CI, 0.4-5.8) CR and 13.5% (95% CI, 8.5-20.1) PR; in PD-L1– pts, ORR was 5.5% (95% CI, 2.0-11.6), with 1.8% (95% CI, 0.2-6.5) CR and 3.7% (95% CI, 1.0-9.1) PR. In 3L pts with PD-L1+ tumors, ORR was 21.3% (95% CI, 12.7-32.3), with 4.0% (95% CI, 0.8-11.2) CR; in 3L pts with PD-L1– tumors, ORR was 6.9% (95% CI, 1.9-16.7), with 3.4% (95% CI, 0.4-11.9) CR. Grade 3-5 treatment-related AEs (TRAEs) occurred in 43 pts (16.6%). TRAEs led to discontinuation in 2 pts (abnormal LFT, bile duct stenosis) and were fatal in 2 pts (acute kidney injury, pleural effusion).

Conclusions:

Pembro showed encouraging efficacy and manageable safety after $2 prior lines of therapy in pts with advanced G/GEJ cancer in this large phase 2 trial. Survival and additional biomarker data, including MSI status, will be presented. Clinical trial information: NCT02335411.

All content © 2017 American Society of Clinical Oncology. All rights reserved.

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