statistically significant: Median OS was 29.2 months (95% CI: 24.2, not estimable [NE]) and 23 months (95% CI: 15.1, 27.9) in the respective arms (hazard ratio 0.70 [95% CI: 0.49, 1.01]). Forty-five percent of patients who received placebo received retifanlimab-dlwr after disease progression. ORR was 56% (95% CI: 48, 64) and 44% (95% CI: 36, 52) in the respective arms. The FDA also wrote in a press release that the efficacy of retifanlimab-dlwr as a single agent was evaluated in POD1UM-202 (NCT03597295), an open-label, multicenter, single-arm trial in 94 patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. Those patients received retifanlimab-dlwr 500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity or up to 24 months. The major efficacy outcome measures were ORR and DOR as assessed by an independent review committee (IRC) according to RECIST v1.1. ORR was 14% (95% CI: 8, 23), and median DOR was 9.5 months (95% CI: 4.4, not estimable [NE]). The prescribing information for retifanlimab-dlwr includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT and embryo-fetal toxicity, according to the FDA. The recommended retifanlimab-dlwr dose in combination with carboplatin and paclitaxel is 500 mg every 4 weeks until disease progression, unacceptable toxicity or up to 12 months. The recommended dose of retifanlimab-dlwr as a single agent is 500 mg every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months. Refer to the prescribing information for carboplatin and paclitaxel for recommended dosing information in combination with retifanlimab. The POD1UM-303/InterAACT-2 study, published in Lancet in June 2025 noted that carboplatin with weekly paclitaxel was the current recommended regi- men based on the phase 2 InterAACT trial results and European Society for Medical Oncology and National Comprehensive Cancer Network guidelines for SCAC. “However, the progression-free survival and overall survival with this regimen are short (8·1 months and 20·0 months, respectively),” the researchers wrote. “Retifanlimab is an anti-programmed cell death-1 (PD- 1) humanized monoclonal antibody that is approved in the USA and Europe for advanced Merkel cell carci- noma. Retifanlimab showed improved clinical responses and a favorable safety profile compared with previous sal- vage chemotherapy in a phase 2 study of patients with platinum-refractory advanced SCAC.”4 They added that, although the current standard-of- care platinum-based chemotherapy provides high initial response rates, “patients commonly experience disease progression and have short median survival times, high- lighting an unmet medical need. To our knowledge, this is the first and largest well controlled trial in recurrent or metastatic SCAC, a rare disease. The addition of reti- fanlimab to carboplatin-paclitaxel led to significantly longer median progression-free survival than placebo plus carboplatin-paclitaxel, with a consistent benefit in favour of retifanlimab plus chemotherapy observed for all subgroup comparisons.” The study team also pointed out that, at the interim analysis and despite the immature data, their results suggested a possible improvement of overall survival. “Similar rates of carboplatin-paclitaxel dose interruption were observed in both groups, with higher rates of serious and grade ≥3 adverse events observed with retifanlimab that could be managed with standard measures and did not compromise administration of carboplatin-pacli- taxel,” according to their report. According to the study, about 14% of anal cancers are metastatic at diagnosis, and about 40% of patients with localized SCAC will progress after initial chemoradia- tion. The 5-year relative survival rate is approximately 36% for patients with distant metastasis. “In addition to compromised survival, patients with advanced anal can- cer report bleeding, rectal and abdominal pain, and feel- ing stigmatised, all of which lead to a diminished quality of life,” the researchers wrote. They concluded that “retifanlimab improves clinical outcomes with a manageable safety profile when added to standard-of-care chemotherapy in advanced SCAC. Retifanlimab with carboplatin plus paclitaxel should be considered the new standard of care for this difficult-to- treat disease.” 1 Sanger CB, Xu Y, Carchman E, Lawson EH, Heise CP, Striker R, Voils CI. Prevalence of High-Grade Anal Dysplasia and Anal Cancer in Veterans Living With HIV and CD4/CD8 Ratio as a Marker For Increased Risk: A Regional Retrospective Cohort Study. Dis Colon Rectum. 2021 Jul 1;64(7):805-811. doi: 10.1097/DCR.0000000000002009. PMID: 34086000; PMCID: PMC8186795. 2Sanger CB, Kalbfell E, Cherney-Stafford L, Striker R, Alagoz E. A Qualitative Study of Barriers to Anal Cancer Screenings in US Veterans Living with HIV. AIDS Patient Care and STDs. 2023;37(9):436-446. doi:10.1089/ apc.2023.0144. 3Palefsky JM, Lee JY, Jay N, Goldstone SE, et. Al. ; ANCHOR Investigators Group. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. N Engl J Med. 2022 Jun 16;386(24):2273-2282. doi: 10.1056/NEJMoa2201048. PMID: 35704479; PMCID: PMC9717677. 4Rao S, Samalin-Scalzi E, Evesque L, Ben Abdelghani M, et. Al. ; POD1UM-303/InterAACT-2 study investigators. Retifanlimab with carboplatin and paclitaxel for locally recurrent or metastatic squamous cell carcinoma of the anal canal (POD1UM-303/InterAACT-2): a global, phase 3 randomized controlled trial. Lancet. 2025 Jun 14;405(10495):2144-2152. doi: 10.1016/S0140-6736(25)00631-2. PMID: 40517007. 2 0 2 6 C O M P E N D I U M O F F E D E R A L M E D I C I N E 7
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