New data presented at this year’s virtual ESMO 2020 Congress have shown that immunotherapy is beneficial for patients with gastric and oesophageal cancers who currently have poor survival. Immune therapy would be a big change in treatment, since immune checkpoint inhibitors are not yet approved for early therapy in Western countries. Three studies provide evidence, based on different patient populations and different immune checkpoint inhibitors used as first-line therapy.
The CheckMate 649 trial evaluated nivolumab plus chemotherapy versus chemotherapy alone as first-line treatment in patients with non-HER2-positive advanced gastric cancer, gastro-oesophageal junction cancer, or oesophageal cancer – all with adenocarcinoma histology. The results show that nivolumab and chemotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with PD-L1 combined positive score (CPS) >five tumours. Improvements were also observed in patients with PD-L1 CPS >one tumours and in the overall patient population. Additional analysis of subgroups and biomarkers (eg, MSIHigh) are planned to better characterise the efficacy benefit in patients across all CPS cut-offs.
The ATTRACTION 4 trial was similar to CheckMate 649 except for two important differences: It was performed only in Asian patients and the primary endpoints were designed for all-comers, rather than a specific CPS value. First-line treatment with nivolumab plus chemotherapy improved the co-primary PFS endpoint, but not OS. “The improvement in progression-free survival was clinically relevant and the trial strongly supports the results of CheckMate 649,” said Prof Salah-Eddin Al-Batran, Director, Institute of Clinical Cancer Research, Frankfurt, Germany, and ESMO 2020 upper GI track chair. “Overall survival was not improved, possibly because all-comers were treated or because patients in Asia receive more subsequent therapies than Western populations.”
The KEYNOTE 590 trial examined first-line chemotherapy, with or without pembrolizumab, in patients with squamous cell carcinoma of the oesophagus, adenocarcinoma of the oesophagus, or Siewert type 1 gastro-oesophageal junction adenocarcinoma. It demonstrated that pembrolizumab plus chemotherapy improved OS in patients with squamous cell carcinoma of the oesophagus with PD-L1 CPS >10 tumours, all squamous cell carcinomas, all patients with CPS >10, and the study population as a whole. PFS was also improved. Most oesophageal cancer patients in the trial had squamous cell carcinoma (73 per cent) and those with adenocarcinoma were a small subgroup. The results in the subgroup of patients with adenocarcinoma were an experimental analysis, but in the adenocarcinoma subgroup, median OS was 11.6 months and 9.9 months (HR=0.74), and median PFS was 6.3 months and 5.7 months (HR=0.63) in the pembro+chemo and chemo group, respectively. The OS- and PFS-benefit observed in the adenocarcinoma subgroup was consistent with the benefit observed in the overall patient population.
Commenting on the findings, Prof Al-Batran said: “I expect that KEYNOTE-590 will change practice for patients with metastatic squamous cell carcinoma or adenocarcinoma of the oesophagus who have PD-L1 CPS >10 tumours, for whom pembrolizumab added to chemotherapy will become the standard of care in the first-line.”