Addition of an immune checkpoint inhibitor reduces the risk of disease progression for select patients with anal cancer

Abstract

The addition of the immune checkpoint inhibitor retifanlimab to standard-of-care chemotherapy significantly improved progression-free survival (PFS) in patients with previously untreated and inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC), according to a study presented at the 2024 European Society for Medical Oncology annual meeting in Barcelona.¹

Findings from the international phase 3 POD1UM-303/InterAACT 2 study show that patients with inoperable locally recurrent or metastatic SCAC treated with the combination of retifanlimab and standard-of-care chemotherapy (carboplatin and paclitaxel) had a 37% reduced risk of disease progression in comparison with patients treated with the standard of care alone (hazard ratio, 0.63; 95% CI, 0.47–0.84; p = .0006). The median PFS was 9.3 months for the retifanlimab–chemotherapy group and 7.4 months for the chemotherapy-alone group.

A trend in overall survival (OS) also was found. The median OS was 29.2 and 23.0 months for the retifanlimab–chemotherapy and chemotherapy-alone groups, respectively, with a hazard ratio of 0.70 (95% CI, 0.49–1.01; p = .0273).

The findings are based on 308 patients randomized 1:1 to carboplatin and paclitaxel (six cycles) plus a placebo or plus retifanlimab (500 mg delivered intravenously every 4 weeks). Along with meeting its primary endpoint of PFS, the study showed that the combination regimen was well tolerated with no new safety signals. Immune-related side effects linked to retifanlimab included thyroid dysfunction, adrenal insufficiency, and skin toxicity.

Sheela Rao, MBBS, MD, a consultant medical oncologist in the Gastrointestinal Unit at the Royal Marsden Hospital in Sutton, United Kingdom, who presented the findings, said in a follow-up interview that the findings represent a potentially new standard of care for a disease for which there are very few trials. “So, this really does offer a new treatment option for our patients,” she said.²

Commenting on the study, Cathy Eng, MD, the David H. Johnson Endowed Chair in Surgical and Medical Oncology at Vanderbilt–Ingram Cancer Center, says that the findings suggest a potential role for immune checkpoint inhibition for newly diagnosed locally advanced or metastatic anal cancer that is surgically unresectable.

“Oncologists should be made aware that there is promising data of immune checkpoint inhibition with carbo/paclitaxel that may result in a new indication based on progression-free survival,” she says.

Pointing to the National Cancer Institute–sponsored phase 3 EA2176 study in the United States, which has just completed enrollment, she says that if that study is positive, it will “further validate the role of immune checkpoint inhibition in newly diagnosed surgically unresectable locally advanced metastatic anal cancer.”