Gastroenterology Xagena

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ESMO: Pembrolizumab, promising response rate in pretreated metastatic gastric cancer

Pembrolizumab ( Keytruda ) has shown a promising response rate in patients with pretreated metastatic gastric cancer, according to results from the KEYNOTE-059 trial presented at the ESMO 2017 Congress in Madrid.

The expected survival of patients with metastatic gastric cancer is less than one year. Very few new drugs have been approved for this disease in the past decade.
The phase II KEYNOTE-059 is one of the largest studies to investigate immunotherapy in recurrent or metastatic gastric cancer.

The study included three cohorts: 1) 259 patients with metastatic gastric cancer who received the programmed death 1 ( PD-1 ) inhibitor Pembrolizumab alone, after pretreatment with two or more lines of chemotherapy; 2) 25 patients with newly diagnosed metastatic gastric cancer who received a combination of Pembrolizumab and chemotherapy; 3) 31 patients with newly diagnosed metastatic gastric cancer who received Pembrolizumab alone.

The primary endpoints were safety ( all three cohorts ) and objective response rate ( cohorts one and three ).

After a median follow-up of six months, the investigators found an overall objective response rate of 12% with Pembrolizumab alone in the pretreated patients ( cohort one ).
Patients who expressed programmed death-ligand 1 ( PD-L1 ) were more likely to respond than those who did not, with objective response rates of 16% and 6%, respectively.
Many of the responses were durable.
Grade 3 to 5 treatment-related adverse events occurred in 18% of patients in cohort one and 3% had to discontinue treatment as a result.

The data have shown that the tumours were sufficiently shrunk to warrant a response, particularly in those patients who had PD-L1 expression, and the drug was safe.
The expected response rate in these heavily pretreated patients was close to zero so the findings are encouraging.

In patients with newly diagnosed metastatic cancer, both the combination therapy ( cohort two ) and Pembrolizumab alone ( cohort three ) were safe and showed some promising activity.

There is currently no standard of care for metastatic gastric cancer treated in the third line or beyond. The KEYNOTE-059 cohort 1 results confirm that the efficacy previously reported for the PD-1 inhibitor Nivolumab in patients from East Asia in the ONO-4538 randomised trial can be applied to Western populations.

Researchers cautioned that while the toxicity profile of Pembrolizumab looked quite favourable in KEYNOTE-059, it could be that patients had not been treated long enough to experience side effects.
Unlike with chemotherapy, toxicities from immunotherapy tend to occur later on.

Further research should focus on refining the PD-L1 biomarker and searching for better biomarkers to tell us who benefits from these therapies. ( Xagena )

Source: European Society for Medical Oncology ( ESMO ), 2017