The European Medicines Agency (EMA) has issued a positive opinion recommending that retifanlimab (Zynyz) be approved for an expanded indication to treat adults with advanced squamous cell carcinoma of the anal canal (SCAC). If authorised, it would become the first immunotherapy-based regimen available in the EU for this population, marking a significant advance in a field with limited therapeutic options.
A Rare but Increasingly Common Cancer
SCAC represents the predominant form of anal cancer, making up roughly 85% of cases. Although considered rare, it affects about 10,000 individuals annually, and incidence continues to climb—largely driven by persistent infection with high‑risk HPV types such as HPV‑16 and HPV‑18. Approximately one in four patients eventually develop metastatic disease, which is associated with drastically poorer prognoses and a five‑year survival rate of about 36%.
Current treatment options for SCAC in earlier stages rely primarily on chemoradiation. Despite this, as many as 60% of patients experience relapse within five years. For metastatic disease, available therapies have historically been palliative in nature, centred on chemotherapy with modest survival benefits. The absence of EU‑approved treatments specifically targeting SCAC has been a notable gap in cancer care.
How Retifanlimab Works
Retifanlimab is a monoclonal antibody that targets PD‑1, a receptor on T cells that, when engaged by PD‑L1 expressed on tumour cells, suppresses immune activity. By blocking PD‑1, the drug helps reactivate T‑cell responses against cancer cells. When used alongside carboplatin and paclitaxel, retifanlimab is intended to enhance the immune system’s ability to mount a sustained antitumor attack.
Clinical Trial Results
EMA’s recommendation stems from findings of a randomized, double‑blind trial involving 308 adults with unresectable, metastatic, or locally recurrent SCAC. All participants received standard carboplatin–paclitaxel chemotherapy, along with either retifanlimab or placebo.
Key findings include:
- Progression‑free survival: Patients receiving retifanlimab lived a median of 9.3 months without disease worsening versus 7.4 months in the placebo group.
- Overall survival: Median survival reached 32.8 months in the retifanlimab arm compared with 22.2 months for placebo, though this difference did not reach statistical significance.
While overall survival results were not conclusive, EMA determined that the combined dataset—particularly the improvement in progression‑free survival—supports a meaningful clinical benefit.
Safety Profile
The most frequently reported side effects in the combination-treated group included:
- Neutropenia
- Lymphopenia
- Rash and pruritus
- Hypothyroidism
- Elevated alanine aminotransferase levels
These adverse events are consistent with known effects of immune checkpoint inhibitors and taxane–platinum chemotherapy.
Next Steps Toward Patient Access
The EMA’s opinion now moves to the European Commission, which will decide whether to grant an EU‑wide extension of indication for Zynyz. If approved, pricing and reimbursement decisions will then be made at the level of individual Member States.
If fully authorised, retifanlimab could become the first immunotherapy available for advanced SCAC in Europe—marking a critical milestone for a patient population with few effective treatment options.
