Pembrolizumab with chemo improves survival in oesophageal cancerDecember 17, 2020
The checkpoint inhibitor pembrolizumab (Keytruda, Merck) with chemotherapy showed an improved overall survival (OS) in patients with previously untreated advanced oesophageal squamous cell carcinoma (ESCC), oesophagal adenocarcinoma (EAC) or esophagogastric junction adenocarcinoma (EGJ). Benefits were greatest in patients with high expression of programmed death ligand-1 (PD-L1), the check-point target of pembrolizumab.
The phase 3 KEYNOTE-590 trial involved 749 patients with unresectable or metastatic ESCC, EAC or Siewert type 1 EGJ. Most patients were male (83%) and had ESCC (73%). Patients were randomly assigned to receive 200 mg of pembrolizumab or placebo every three weeks. All patients received cisplatin and 5-fluorouracil in conventional doses on a 21-day cycle.
After a median follow-up of 10.8 months, the OS benefit was significant regardless of the CPS score. The hazard ratio (HR) for this outcome was reduced in the whole study population by 27% (HR, 0.73; P<0.0001). In the subgroup with a CPS of at least 10, the risk reduction was 43% (HR, 0.57; P<0.0001)
There also were large advantages among patients randomized to receive pembrolizumab relative to those receiving chemotherapy alone for progression-free survival (HR, 0.65; P<0.0001) and objective response rate (45.0% vs. 29.3%; P<0.0001).
Adverse events of grade 3 or higher were modestly higher in the group that received pembrolizumab. The types of toxicities were similar in the two groups, although immune-mediated adverse events and injection-site reactions were more frequent in the group receiving pembrolizumab. Trial discontinuation due to an AE was greater in the pembrolizumab arm (19% vs. 12%).
The advantage of pembrolizumab over chemotherapy alone was of a similar magnitude in the ESCC and EGJ groups. According to the findings, the addition of pembrolizumab to chemotherapy is a reasonable strategy in advanced ESCC, EAC or EGJ, but it may not be considered a standard for those with low PD-L1 expression. The results were presented at the Virtual ESMO Congress 2020.