Reason for request

New indication

Key points

Unfavourable opinion for reimbursement, as monotherapy, in the treatment of adult patients with unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC) after prior fluoropyrimidine- and platinum-based combination chemotherapy.

Role in the care pathway?

Therapeutic strategies for oesophageal squamous cell carcinoma are defined based on the histological type (squamous cell/adenocarcinoma) and stage of the cancer. In patients with unresectable advanced, metastatic oesophageal squamous cell carcinoma, use of systemic treatment alone (palliative chemotherapy) is the standard treatment.

The main medicinal products used in combination are cisplatin and 5- fluorouracil. Other regimens, such as the FOLFOX regimen combining fluorouracil-oxaliplatin-folinic acid, are sometimes used as a treatment option.

In certain metastatic gastro-oesophageal junction (GEJC) adenocarcinomas over-expressing HER 2, treatment with a targeted therapy (trastuzumab) may also be proposed in combination with chemotherapy.

Apart from nivolumab (the subject of the present assessment), no other medicinal products currently have an MA specifically as second-line therapy in unresectable advanced, recurrent or metastatic oesophageal squamous cell carcinoma after a first line of chemotherapy. However, in this situation ESMO (2016) European guidelines and NCCN (2021) American guidelines recommend, in particular, taxanes (docetaxel or paclitaxel) as monotherapy in eligible patients. Patients in poor general condition are managed by supportive care.

Role of the medicinal product in the care pathway

Considering, on the one hand:

  • the demonstrated superiority of nivolumab versus monotherapy with taxanes (docetaxel or paclitaxel) on overall survival (primary endpoint) in a phase 3, randomised, open-label study (ATTRACTION-III) with a modest absolute improvement of 2.5 months and survival curves that cross (additional effect size difficult to interpret
  • the more favourable safety profile of nivolumab compared to taxanes (AE grades 3-4: 38.3% vs 70.7%; serious AEs: 32.5% vs 63.2%; AE having led to treatment discontinuation: 13.9% vs 15.9%) with, however, more frequent grade 5 AEs with nivolumab: 3.3% versus 2.4%);

But taking into account, on the other hand:

  • concerns related to the excess mortality observed with nivolumab compared to chemotherapy in the 5 months following randomisation in a context in which no specific factor associated with these early deaths could be identified;
  • the non-guaranteed transposability of the results to French patients (patients predominantly native to Asia [95.7%]) and the exclusion of patients with a poor general condition (ECOG score

≥ 2), who are nonetheless the most representative in routine practice at this stage of the disease;

  • the absence of any possible conclusion with respect to progression-free survival given the early interruption of the ranked analysis sequence;
  • the absence of a formal conclusion on quality of life (exploratory endpoint and open-label study);

the Transparency Committee considers that, on the basis of currently available data, OPDIVO (nivolumab), as monotherapy, has no role in the care pathway for oesophageal squamous cell carcinoma (OSCC) in the treatment of adult patients with unresectable advanced, recurrent or metastatic OSCC after prior fluoropyrimidine- and platinum-based combination chemotherapy.

Clinical Benefit


The Committee deems that the clinical benefit of OPDIVO (nivolumab) is insufficient to justify its public funding cover in the new MA indication.


Clinical Added Value


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