EMA approves two combination-treatments for an aggressive oesophageal cancer
The two most common types of oesophageal cancer are squamous cell carcinoma (OSCC) and adenocarcinoma (OAC). The majority of oesophageal cancers belong to the OSCC sub-type, accounting for more than 85% of all oesophageal cancers.1
Advanced OSCC is an aggressive disease with a poor prognosis. The latest approval, by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) of nivolumab (Opdivo) plus ipilimumab (Yervoy) as a first-line treatment for patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%, is forward momentum in providing another promising treatment option for patients awaiting new therapeutics in the E.U.
This positive recommendation is based on encouraging results demonstrated in the CheckMate 648 trial. The CheckMate 648 trial is a randomized phase III, global clinical trial, which compared the overall survival (OS) and progression-free survival (PFS) between two groups of patients treated with nivolumab plus ipilimumab or treated with nivolumab plus fluorouracile and cisplatine (chemotherapies) respectively, to a group treated with chemotherapy alone. All the participants in the clinical trial had previously untreated, unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma.
Results from the trial revealed that treatment with nivolumab plus ipilimumab had a statistically significant and clinically meaningful OS benefit compared to chemotherapy alone in patients with unresectable advanced, recurrent, or metastatic OSCC with PD-L1 expression ≥1%, showing a median OS of 13.7 months compared to 9.1 months for those receiving chemotherapy alone (98.6% confidence interval (CI): 0.46 to 0.90; p-value = 0.001).
Of importance to note, the treatment with nivolumab plus chemotherapy also had a statistically significant and clinically meaningful OS benefit compared to chemotherapy alone with a median of 15.4 months OS in the nivolumab plus chemotherapy group compared to 9.1 months in the chemotherapy group (99.5% CI: 0.37 to 0.80; p-value <0.001). Furthermore, this combination of nivolumab plus chemotherapy revealed a statistically significant and clinically meaningful improvement in the primary endpoint of PFS and a clinically meaningful increase in objective response rate (ORR) in patients whose tumours express PD-L1. These positive results have also gained EMA approval recommendation for nivolumab plus chemotherapy as a first-line treatment for patients with unresectable advanced, recurrent, or metastatic oesophageal squamous cell carcinoma with tumour cell PD-L1 expression ≥ 1%.
The safety profile of nivolumab plus ipilimumab, as well nivolumab plus chemotherapy was consistent with previously reported studies. Regarding safety, the most common (occurring in 10% or more) treatment-related adverse events (TRAEs) for the chemotherapy-containing groups were nausea, decreased appetite, and stomatitis. For the nivolumab plus ipilimumab group, common TRAEs were rash, pruitis, and hypothyroidism. Notably, incidence of TRAEs was consistent with all treated patients across all arms for patients whose tumour cell had PD-L1 expression 1%.
The European Commission’s (EC) review and approval of nivolumab plus ipilimumab, and nivolumab plus chemotherapy represents two new potential first line treatment options for patients with advanced oesophageal squamous cell carcinoma, based on the results of CheckMate-648. It allows for the use of the approved combinations in the 27 member states of the European Union, as well as Iceland, Liechtenstein, and Norway. The next step is for each country to make this new therapy combination available through their national health care systems. This process varies significantly from country to country, with some country reimbursement approvals happening within a few months after the EC approval and others after several years.
About nivolumab and ipilimumab
Both nivolumab and ipilimumab are immunotherapy cancer drugs; they may help a person’s own immune system fight cancer. Both drugs are also immune checkpoint inhibitors. Immune checkpoints engage when proteins on the surface of immune cells called T-cells recognize and bind to partner proteins on other cells, preventing an immune response from being so strong that it destroys healthy cells in the body. Some cancer cells maintain the ability to produce immune checkpoints thus, they cannot be attacked by the immune system. Immune checkpoint inhibitors block checkpoint proteins from binding with their partner proteins, hence restoring and enhancing the body’s anti-tumor immune response.
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1. World Cancer Research Fund, American Institute for Cancer Research, Diet, nutrition, physical activity and stomach cancer, 2018, https://www.wcrf.org/ sites/default/files/Stomach-cancer-report.pdf