The EC Approves Nivolumab Plus Chemotherapy as First Line Treatment for Oesophageal Cancer
On October 21 the European Commission (EC) approved the use of nivolumab (Opdivo®) plus chemotherapy for the first line treatment of adult patients with HER2-negative advanced or metastatic gastric, gastroesophageal junction, or oesophageal adenocarcinoma whose tumours express PD-L1. These cancers have a median overall survival (OS) of less than a year. 1, 2 With this approval patients have access to a treatment regime that can prolong their life.
The EC approval was based on the results of the CheckMate 649, a phase III, global clinical trial, which examined the overall survival between two groups of patients: a group treated with nivolumab and chemotherapy and a group treated with chemotherapy alone. All the participants in the clinical trial had previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Results from the trial showed a statistically significant and clinically meaningful improvement in OS and progression-free survival (PFS) in patients from the first group that was treated with nivolumab and chemotherapy. The median OS was 14,4 months in patients receiving nivolumab plus chemotherapy (95% Confidence Interval [CI]: 13,1–16,3) compared to 11,1 months (95% CI: 10,0–12,1) in patients receiving chemotherapy alone and the median PFS was 8,31 months in patients receiving nivolumab plus chemotherapy (95% CI: 7,03 –9,26) vs. 6,05 months (95% CI: 5,55 –6,90) in patients receiving chemotherapy alone (Hazard Ratio [HR]: 0,68; 95% CI: 0,59 –0,79). The most common adverse events related to treatment included nausea, diarrhoea and peripheral neuropathy and were experienced by patients in both treatment groups. Among all treated patients, 59% treated with nivolumab plus chemotherapy and 44% treated with chemotherapy had grade 3–4 adverse events related to treatment.3
Nivolumab inhibits the PD-L1 (Programmed-Death-Ligand1) function and helps restore anti-tumour immune response. PD-L1 is a protein that, when expressed on the surface of cells, helps keep the lymphocytes T cells from attacking them so that cancers expressing PD-L1 are protecting themselves from the anti-tumour action of lymphocytes T. By harnessing the body’s own immune system to fight cancer, nivolumab has become an important treatment option across multiple cancers. In oesophageal cancer, it is also approved as a monotherapy (used on its own) for previously treated patients.
The European Commission approval allows for the use of nivolumab in combination with chemotherapy 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 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 European Commission approval and others after several years.4
1. Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) + Chemotherapy for Patients with HER2 Negative, Advanced or Metastatic Gastric, Gastroesophageal Junction or Esophageal Adenocarcinoma whose Tumors Express PD-L1 with CPS ≥ 5. Press release. Bristol Myers Squibb. Oct. 21, 2021. Accessed November 22, 2021.
2. https://www.ema.europa.eu/en/medicines/human/EPAR/opdivo. Access November 22, 2021.
3. Yelena Y Janjigian, Kohei Shitara, Markus Moehler, Marcelo Garrido, Pamela Salman, Lin Shen, Lucjan Wyrwicz, et al. -line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. doi: 10.1016/S0140-6736(21)00797-2.
4. Wilking N, et al. Achieving equal and timely access to innovative anticancer drugs in the European Union (EU): summary of a multidisciplinary CECOG-driven roundtable discussion with a focus on Eastern and South-Eastern EU countries. ESMO Open. 2019 Nov 13;4(6):e000550. doi: 10.1136/esmoopen-2019-000550.