Dr Kim on Upfront vs Second-Line Use of Retifanlimab in Metastatic SCAC

"Based on the data we have seen with the PODIUM-303 study, it clearly makes sense to use [retifanlimab in the frontline]. You are not only getting the benefit of PFS and a higher response rate, but [median] OS is over 20 months. By giving it upfront, you are ensuring that the patient will get exposed [to retifanlimab] at the beginning [of treatment] and not the end.”

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 considerations for utilizing retifanlimab-dlwr (Zynyz)–based therapy in the frontline setting or saving it for later use as a single agent in the second line.

For adult patients with inoperable locally recurrent or metastatic SCAC, retifanlimab is currently indicated for use in the frontline setting in combination with carboplatin and paclitaxel, as well as a single agent for second-line therapy for those who experienced disease progression or were intolerant to platinum-based chemotherapy. Of note, the May 2025 FDA approval of retifanlimab plus chemotherapy for first-line, inoperable locally recurrent or metastatic SCAC was supported by data from the phase 3 POD1UM-303/InterAACT2 trial (NCT04472429). This study demonstrated that the addition of retifanlimab to carboplatin and paclitaxel significantly increased median progression-free survival to 9.3 months (95% CI, 7.5-11.3) compared with 7.4 months (95% CI, 7.1-7.7) for those receiving placebo plus chemotherapy (HR, 0.63; 95% CI, 0.47-0.84; P = .0006). Furthermore, although the overall survival (OS) benefit was not statistically significant at the time of interim analysis, the median OS was 29.2 months (95% CI, 24.2-not evaluable) in the retifanlimab arm vs 23 months (95% CI, 15.1-27.9) in the placebo arm (HR, 0.70; 95% CI, 0.49-1.01; P = .0273)

Kim emphasized that using this combination at the beginning of treatment is the most logical strategy for eligible patients. By providing immunotherapy upfront, both the response rate and PFS benefit can be maximized, ensuring that patients receive exposure to the most effective agents early in their disease course rather than waiting for later-line settings, Kim explained. He noted that reserving retifanlimab as a single agent for the second line is primarily appropriate for patients who missed the opportunity for immunotherapy in the first line.

Ultimately, although certain conditions such as autoimmune disease represent a relative contraindication, Kim concluded that for most patients with advanced SCAC, there is no clinical reason to withhold frontline immunotherapy. These findings reinforce the value of incorporating retifanlimab into the standard of care to optimize long-term patient outcomes, Kim concluded.