veterans, the VA recommends anal cancer screenings annually for patients with HIV. The screening rate has traditionally been low, however, at around 15%. Semi- structured interviews with VHA providers as part of a 2023 study determined that many clinicians lacked knowledge of screening protocols. Furthermore, even knowledgeable providers often lacked needed resources, including swabs, clinic space, reliable pathology, access to high-resolution anoscopy or leadership support to implement a screening program, according to the researchers from the W.S. Middleton Memorial Veterans’ Hospital and the University of Wisconsin School of Medicine, both in Madison.2 The report in AIDS Patient Care & STDs also noted that providers mentioned competing priorities in the care of veterans with HIV infection and lack of skilled/ trained personnel to perform the tests. The study team said additional factors included patient discomfort with screening exams. “Anal cancer screening protocols are recommended but not widely adopted in VA,” the authors wrote. “There is a critical need to address barriers to anal cancer screenings in veterans. The TDF domains identified align with five intervention domains to target, including education, training, resource/environment, delineation of provider roles and improved counseling efforts. Targeting these barriers may help improve the uptake of anal cancer screenings within VA.” Most experts now urge rigorous follow-up with pro- cedural examinations after dysplasia is detected, with standard or high-resolution anoscopy (HRA), biop- sies and excision/ablation of dysplastic lesions. Yet, recommendations for screening didn’t become wide- spread until after the ANCHOR study was published in the NEJM in 2022.The results of the large, Phase 3 study led by researchers at UC San Francisco, found that treating precursor anal cancer lesions can signifi- cantly reduce the risk of progression to full blown anal cancer among people living with HIV. The Anal Cancer/ HSIL Outcomes Research (ANCHOR) study deter- mined that removing high-grade squamous intraepithe- lial lesions (HSIL) reduced the chances of progression to anal cancer.3 Once lesions progressed to anal cancer, the proto- col has been to use chemoradiation, a combination of external beam radiation (often IMRT) with chemother- apy (typically 5-fluorouracil (5-FU) plus mitomycin-C). Surgery has been reserved for smaller, localized tumors, or as “salvage” surgery, if cancer persists or returns after chemoradiation. The treatment goal is to eliminate the tumor while preserving sphincter function. The options were sparse, however, for more advanced cancer until recently. Last year, the Food and Drug Administration approved retifanlimab-dlwr with carboplatin and pacli- taxel for the first-line treatment of adults with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). The FDA also approved reti- fanlimab-dlwr, as a single agent, for adults with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy. The product is marketed by Incyte Corporation as Zynyz. “Patients with inoperable locally recurrent or meta- static anal cancer have historically faced poor five- year survival rates and limited treatment options. The POD1UM data highlight the potential of Zynyz to be a meaningful new option, and notably demonstrate that the addition of Zynyz to platinum-based chemotherapy sig- nificantly improves progression-free survival,” Marwan Fakih, MD, professor, medical oncology and therapeutics research, associate director of clinical sciences, medical director, Briskin Center for Clinical Research, division chief, GI medical oncology, co-director, gastrointestinal cancer program at the City of Hope in Duarte, CA, said at the time. “This approval marks an important advance- ment as it makes a new treatment approach available for this challenging cancer.” The efficacy of retifanlimab-dlwr with carbopla- tin and paclitaxel was evaluated in POD1UM-303/ InterAACT 2 (NCT04472429), a randomized, multi- center, double-blind trial in 308 patients with chemo- therapy-naïve inoperable locally recurrent or metastatic SCAC. Patients received carboplatin AUC of 5 on Day 1, and paclitaxel 80 mg/m2 on Days 1, 8 and 15 for 6 cycles and were randomized (1:1) to receive either: • retifanlimab-dlwr 500 mg intravenously every 4 weeks or • placebo intravenously every 4 weeks. The major efficacy outcome measure was progression- free survival (PFS) as assessed by blinded independent central review (BICR) according to RECIST v1.1, with overall survival (OS) as a key secondary endpoint. Additional efficacy outcome measures were overall response rate (ORR) and duration of response (DOR) as assessed by BICR. Median PFS was 9.3 months (95% CI: 7.5, 11.3) in the retifanlimab-dlwr arm and 7.4 months (95% CI: 7.1, 7.7) in the placebo arm (hazard ratio 0.63 [95% CI: 0.47, 0.84] p-value 0.0006). The FDA noted that interim OS results were not 6
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