First immunotherapy-based treatment recommended for advanced anal cancer

30 January 2026

Zynyz provides an option for adults with squamous cell carcinoma of the anal canal

EMA has recommended extending the therapeutic indication of Zynyz (retifanlimab) to include treatment of adults with squamous cell carcinoma of the anal canal (SCAC) that cannot be removed by surgery and is metastatic or locally recurrent. It is used in combination with carboplatin and paclitaxel (chemotherapy medicines).

SCAC is the most common type of anal cancer, accounting for 85% of all cases. SCAC is a rare, life-threatening cancer affecting around 10,000 people each year. However, its incidence has increased by approximately 3% per year over the past decade, mainly due to the spread of high-risk strains of human papillomavirus (HPV) that can cause several types of cancer, particularly HPV 16 and 18 [references]. In approximately 25% of people with SCAC, the cancer spreads to other parts of the body. This advanced stage of SCAC is associated with markedly poorer outcomes, with 5-year survival rates of just 36% [references].

There are currently no medicines specifically authorised in the EU for the treatment of adults with SCAC. For SCAC that has not spread to other parts of the body, treatment options are limited to chemotherapy and radiation. However, up to 60% of these patients see their cancer return within 5 years of their initial treatment. The outlook for these patients and for those who are diagnosed with metastatic disease from the outset remains poor, with 5-year survival rates of only 15 to 20%. For metastatic SCAC, treatment typically focuses on palliative care, specifically chemotherapy, to manage symptoms and improve quality of life.

The active substance in Zynyz, retifanlimab, is a monoclonal antibody, a protein that blocks a receptor called PD-1 found on the surface of immune cells known as T cells. Some cancers, including SCAC, can make a protein known as PD-L1 that attaches to the PD-1 receptor on T cells to switch off the activity of the T cells, preventing them from attacking the cancer. By blocking PD-1, retifanlimab stops the cancer switching off the activity of T cells, thereby increasing the immune system’s ability to kill the cancer cells.

EMA’s recommendation is based on the results of a randomised, double-blind clinical trial that included 308 adults with metastatic or locally recurrent SCAC that could not be removed by surgery. All participants were given six cycles of chemotherapy consisting of carboplatin on day 1 and paclitaxel on days 1, 8 and 15. They also received treatment with either Zynyz or placebo (a dummy treatment) every 4 weeks. Half of the patients treated with Zynyz in combination with chemotherapy lived for 9.3 months or longer without their cancer worsening compared with 7.4 months for those receiving placebo in combination with chemotherapy. While half of those treated with Zynyz lived for at least 32.8 months compared with 22.2 months for those receiving placebo, these results were not statistically significant, meaning the difference between the two groups could have happened by chance. Although there is uncertainty about the extent to which Zynyz prolongs life in these patients, EMA concluded that when these findings were considered alongside data on how long patients lived without their cancer worsening, they indicate that the medicine has a beneficial effect.

The most common side effects reported with Zynyz when used in combination with carboplatin and paclitaxel were neutropenia (low levels of neutrophils, a type of white blood cell), pruritus (itching), rash, lymphopenia (low levels of lymphocytes, a type of white blood cell), hypothyroidism (an underactive thyroid gland) and increased levels of the liver enzyme alanine aminotransferase, which may be a sign of liver problems.

The opinion adopted by EMA is an intermediary step on Zynyz’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide extension of the therapeutic indication. Once an extension has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.