Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study

SPS commentary:

At the first interim analysis (median follow-up 22·6 months):

• Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for overall survival in patients with oesophageal squamous cell carcinoma and PD-L1 CPS of 10 or more (median 13.9 vs 8.8 months; HR 0.57 [95% CI 0.43–0.75]; p<0.0001), oesophageal squamous cell carcinoma (12.6 vs 9.8 months; 0.72 [0.60–0.88]; p=0.0006), PD-L1 CPS of 10 or more (13.5 vs 9.4 months; 0.62 [0.49–0.78]; p<0·0001), and in all randomised patients (12.4 vs 9.8 months; 0.73 [0.62–0.86]; p<0.0001).
• Pembrolizumab plus chemotherapy was superior to placebo plus chemotherapy for progression-free survival in patients with oesophageal squamous cell carcinoma (6.3 vs 5.8 months; 0.65 [0.54–0.78]; p<0.0001), PD-L1 CPS of 10 or more (7.5 vs 5.5 months; 0.51 [0.41–0.65]; p<0.0001), and in all randomised patients (6.3 months vs 5.8 months; 0.65 [0.55–0.76]; p<0.0001).

According to a commentary, this study has important implications for the practice of a neglected condition in that it believes pembrolizumab plus chemotherapy should now be considered as a new standard of care in first-line settings for patients with advanced oesophageal cancer, where maximal benefits will be seen in those with oesophageal squamous cell carcinoma and those who have tumours with CPS of 10 or more.

In UK, pembrolizumab in combination with platinum and fluoropyrimidine based chemotherapy, is licensed for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the oesophagus or HER-2 negative gastroesophageal junction adenocarcinoma in adults whose tumours express PD-L1 with a CPS ≥ 10.