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KEYNOTE-059 Points To Potential For Pembrolizumab Role In Advanced Gastric Cancer

Pembrolizumab monotherapy is well tolerated and shows efficacy for patients with advanced, previously treated gastric or gastro-oesophageal junction cancer
22 Mar 2018
Immunotherapy;  Gastric Cancer;  Therapy
By Lynda Williams, Senior medwireNews Reporter

medwireNews: Pembrolizumab monotherapy could offer a third-line or later treatment option for advanced gastric or gastro-oesophageal junction cancer, phase II trial findings indicate. 

The KEYNOTE-059 study included 259 patients from 16 countries who were given open-label pembrolizumab 200 mg every 3 weeks until disease progression or unacceptable toxicity. 

After a median of 5.8 months, 11.6% of the patients had achieved a RECIST objective response, including a complete response in 2.3% of the participants. In all, 42.6% of patients who underwent tumour imaging after baseline showed shrinkage of their measurable tumour size.

The median duration of response was 8.4 months and 53.3% of responses were ongoing at the time of data cutoff, the investigators report in JAMA Oncology.

Median progression-free survival (PFS) was 2.0 months, with a 6-month PFS rate of 14.1%. The corresponding values for overall survival were 5.6 months and 46.5%, falling to 23.4% at 12 months.

Safety analysis revealed that 60.2% of patients experienced at least one treatment-related event of any grade, while 17.8% had at least one grade 3–5 treatment-related side effect, with corresponding values for immune-related adverse events of 17.8% and 4.6%. Two patients discontinued therapy after developing bile duct stenosis and abnormal liver function, and there was one death each from kidney injury and pleural effusion that were both thought to be related to treatment.

“These patients have limited treatment options and poor prognosis”, say Charles Fuchs, from Yale School of Medicine in New Haven, Connecticut, USA, and co-investigators, explaining that the KEYNOTE-059 participants had all previously progressed after receiving regimens containing fluoropyrimidine and platinum doublet chemotherapy, and where applicable, trastuzumab.

“The current results suggest that pembrolizumab offers a promising new treatment option, providing high and durable responses, for advanced gastric or gastroesophageal junction adenocarcinoma that progresses after second-line treatment,” they summarise.

In addition, programmed cell death ligand 1 (PD-L1) immunohistochemistry was performed on tissue from surgical resection or biopsy samples taken from primary or metastatic disease in 257 patients; 57.1% of these patients were positive for PD-L1, 42.1% were negative and 0.8% had unknown status.

The objective response rate was 15.5% for the PD–L1-positive patients, with a median duration of response of 16.3 months, versus 6.4% and a median of 6.9 months for those with PD–L1-negative disease.

When patients were profiled using an 18-gene T-cell-inflamed gene expression score, a higher score was significantly associated with pembrolizumab response and there was a significant, if nonlinear, positive relationship between the score and PD-L1 expression.

“These results suggest the potential for T-cell-inflamed gene expression profiling score and PD-L1 expression as biomarkers for treatment selection in the clinic, but confirmation in future trials is warranted”, the team concludes.

Reference 

Fuchs CS, Foi T, Jang RW, et al. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric gastroesophageal junction cancer. Phase 2 clinical KEYNOTE-059 trial. JAMA Oncol; Advance online publication 15 March 2018.
DOI: https://doi.org/10.1001/jamaoncol.2018.0013

Last update: 22 Mar 2018

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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