Promising front-line alternative for advanced gastric or gastroesophageal junction adenocarcinoma

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Front-line pembrolizumab was comparable to standard chemotherapy in select patients with advanced gastric or gastroesophageal junction adenocarcinoma. 39% of patients with HER2-negative, advanced gastric or gastroesophageal junction adenocarcinoma with PD-L1 combined positive scores of 10 or more who received front-line pembrolizumab were alive after 2 years compared with 22% of those who received systemic chemotherapy [1].

The KEYNOTE-062 phase 3 randomised clinical trial achieved its primary endpoint, showing that for patients with PD-L1-positive, HER2-negative, advanced gastric or gastroesophageal junction (GEJ) cancer, initial therapy with pembrolizumab resulted in comparable (non-inferior) overall survival as standard chemotherapy. Additionally, pembrolizumab showed clinically meaningful improvement in overall survival among patients with tumours that had high levels of PD-L1 expression. At 2 years, 39% of patients (all of whom had high PD-L1 levels) that received pembrolizumab alone were alive, compared with 22% of people who received standard chemotherapy. The trial also evaluated combined treatment with pembrolizumab and standard chemotherapy but found this regimen did not improve survival relative to chemotherapy alone.

“This trial shows that front-line pembrolizumab is effective and could provide a new opportunity for people newly diagnosed with advanced gastric or GEJ cancers,” said lead study author Prof. Josep Tabernero, (Vall d’Hebron Barcelona Hospital University Hospital and Institute of Oncology, Spain). “There remains a significant unmet need for treatments for these cancers and our results reinforce the importance of continued research in this field.”

The trial enrolled 763 patients with a median age of 62 and 26% had previous gastric surgery to remove a tumour. In total, 69% had gastric cancer and 30% had GEJ cancer, which are typically very similar types of tumours despite their adjacent locations according to Prof. Tabernero. Investigators focused only on HER2-negative cancers, which studies have shown have a higher chance of recurrence after treatment, to limit factors that could affect outcomes.

In the current trial, all patients had a PD-L1 CPS of one or greater, and 281 (37% of the enrolees) had a score of 10 or more. The investigators randomly assigned patients, in equal numbers, to receive one of three treatment options as initial therapy: intravenous pembrolizumab, pembrolizumab and chemotherapy, or chemotherapy plus placebo. The patients were followed for a median of 11.3 months.

The trial reached its primary endpoint, demonstrating that overall survival for pembrolizumab was non-inferior to standard chemotherapy. A favourable survival outcome was seen among enrolled patients with PD-L1 CPS of 10 or more. Specific findings include:

• Patients with PD-L1 CPS of one or more: Survival was non-inferior to chemotherapy [hazard ratio = 0.91] – median overall survival was 10.6 months for those receiving pembrolizumab compared with 11.1 months for those who received chemotherapy.

• Patients with PD-L1 CPS 10 or more: Survival with pembrolizumab was superior to chemotherapy [hazard ratio = 0.69] – median overall survival was 17.4 months for those receiving pembrolizumab compared with 10.8 months for those receiving chemotherapy. After 2 years, 39% of people taking pembrolizumab were alive compared with 22% of those taking chemotherapy. Overall survival and progression-free survival (time until disease progression), regardless of CPS score, for the combination treatment of pembrolizumab and chemotherapy was comparable to that of chemotherapy alone.

The safety profile of pembrolizumab was consistent with prior experiences of patients who have been treated with it.

  1. Tabernero J. et al. Abstract LBA4007. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. ASCO 2019, 31 May-4 June, Chicago, USA.

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