FOR MANY YEARS, chemotherapy and radiation have remained first-line treatments for people with advanced anal cancer. However, on May 15, 2025, the Food and Drug Administration (FDA) approved an immune checkpoint inhibitor called Zynyz (retifanlimab) to be added to chemotherapy for first-line treatment of advanced squamous cell carcinoma of the anal canal (SCAC).

The approval was based on a study published June 14, 2025, in the Lancet that included 308 people with inoperable locally recurrent or metastatic SCAC. Participants received an IV infusion of either Zynyz or a placebo every four weeks, along with chemotherapy. Those who received Zynyz were alive without cancer progression for a median of 9.3 months, compared with 7.4 months for those who received the placebo infusion. Patients who received a placebo could switch to Zynyz monotherapy if their disease progressed during the clinical trial.

Immune checkpoint inhibitors, like Keytruda (pembrolizumab) and Opdivo (nivolumab), are recommended as second-line treatments for people who have anal cancer that has progressed after chemotherapy and cannot be removed with surgery, according to National Comprehensive Cancer Network (NCCN) guidelines. However, for the first time, the NCCN now recommends an immune checkpoint inhibitor along with chemotherapy as the preferred first-line treatment for metastatic SCAC, says Sheela Rao, an oncologist at the Royal Marsden Hospital in London and the lead author of the Lancet paper. The study findings fill an unmet need for assessing treatment approaches in a cancer that has historically been understudied, she says. “For a long period of time, there weren’t any trials [comparing approaches for advanced SCAC]. There wasn’t enough [clinical data] to know the best treatment,” Rao says.

The FDA approval also included the use of Zynyz alone for adults who have locally recurrent or advanced SCAC that doesn’t respond to or who cannot tolerate chemotherapy. This part of the approval was based on a 2022 study published in ESMO Open that included 94 people with advanced anal cancer who received Zynyz alone. The immunotherapy controlled the disease in close to half of patients and shrank tumors in about 14%.

Marwan Fakih, a researcher and oncologist at City of Hope Comprehensive Cancer Center in Duarte, California, who was not involved in the study, notes immune checkpoint inhibitors, such as Zynyz, offer another option for people who cannot tolerate chemotherapy. Patients may decide to stop chemotherapy due to progressively worsening side effects, such as peripheral neuropathy, which can cause pain, tingling, numbness or muscle weakness in the hands and feet, Fakih says.

Primarily caused by human papillomavirus infection, SCAC represents the most common form of anal cancer. About 14% of people with anal cancer will receive their diagnosis after the cancer has spread to distant organs. Some symptoms of anal cancer, such as rectal bleeding, may be overlooked and can also be a source of embarrassment. In addition, a person with anal cancer “often goes misdiagnosed because people assume it’s other things, like hemorrhoids,” Rao says. “And unless they’re properly examined and reviewed and their symptoms are listened to, that can lead to a later diagnosis, and by doing so, sometimes that can make it more difficult to treat.”