Dr Kim on Advancements With First-Line Immunotherapy and De-escalation Strategies in SCAC

"There is clearly a shift from chemotherapy-only toward a chemo-immunotherapy strategy for eligible patients... Adding PD-1 blockade to standard chemotherapy can translate into a meaningful improvement in overall survival compared with chemotherapy alone."

Richard Kim, MD, the service chief of Medical Gastrointestinal Oncology and a senior member in the Gastrointestinal Oncology Department at Moffitt Cancer Center, as well as a professor of oncology at the University of South Florida College of Medicine, discussed transformative shifts in the treatment paradigm for squamous cell carcinoma of the anal canal (SCAC), in recognition of SCAC Awareness Day.

Kim began by highlighting how the standard of care is rapidly evolving from traditional chemotherapy-only approaches toward more personalized, immunotherapy-inclusive regimens for both advanced and localized disease. The most significant development for advanced disease is the May 2025FDA approval of the PD-1 inhibitor retifanlimab-dlwr (Zynyz) in combination with carboplatin and paclitaxel. This approval for adult patients with inoperable, locally recurrent, or metastatic SCAC was supported by findings from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429).

Kim noted that the trial data have become increasingly mature, demonstrating a high and durable response rate. Critically, a trend toward overall survival (OS) has emerged, favoring the immunotherapy arm by up to 10 months compared with the standard chemotherapy arm alone. For patients who have failed platinum-based first-line therapy, retifanlimab has also received approval as a single agent in the second-line setting. However, ongoing research with PD-L1 inhibition is focused on ensuring eligible patients receive the benefit of checkpoint inhibition as early as possible in their treatment course to maximize OS, Kim noted.

Beyond advanced disease, the field is seeing a move toward personalizing treatment for localized SCAC through radiation de-escalation. Kim pointed to emerging data, including a study suggesting that selected patients with early-stage (T1 or T2) anal cancer can be successfully treated with radiation doses that are lower than the current standard. This approach allows for tailored treatment intensity, potentially reducing long-term toxicities while maintaining efficacy. These advancements represent a new era of precision medicine in SCAC, Kim concluded.