Retifanlimab plus platinum-based chemotherapy may benefit patients with squamous cell anal carcinoma, according to new findings presented by Rao et al at a presidential symposium at the European Society for Medical Oncology (ESMO) Congress 2024 (Abstract LBA2).
Background
The incidence of squamous cell anal carcinoma—an orphan disease—is currently increasing about 3% per year, largely because of endemic human papillomavirus (HPV). Further, the human immunodeficiency virus (HIV) is an important amplifier of squamous cell anal carcinoma, since patients with HIV are 25 to 35 times more likely to develop the disease. Patients with unresectable metastatic squamous cell anal carcinoma often have poor 5-year survival, and there are currently no U.S. Food and Drug Administration–approved treatment options among these patients.
“Advanced [squamous cell anal carcinoma] is an often-neglected, rare condition that, despite its increasing incidence and the often-poor prognosis, has had the same standard-of-care treatment for decades with very few trials,” explained lead study author Sheela Rao, MD, a consultant medical oncologist at The Royal Marsden National Health Service Foundation Trust.
Retifanlimab is a humanized monoclonal antibody targeting PD-1.
Study Methods and Results
In the phase III POD1UM-303/InterAACT2 trial, the researchers randomly assigned 1:1 adult patients with inoperable locally recurrent or metastatic squamous cell anal carcinoma who weren’t previously treated with systemic chemotherapy to receive either 500 mg of intravenous retifanlimab or placebo in combination with carboplatin-paclitaxel during each 28-day cycle for up to 6 months followed by monotherapy for up to 1 year. Crossover to active therapy retifanlimab was allowed in the patients assigned to placebo upon verification of progression by blinded independent central review.
The primary endpoint of the trial was progression-free survival, and the secondary endpoint included overall survival. Secondary objectives included objective response rate, duration of response, disease control rate, safety, and pharmacokinetics.
The researchers discovered that adding retifanlimab to standard-of-care chemotherapy resulted in a clinically meaningful 37% reduction in the risk of cancer progression or death (hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.47–0.84, P = .0006). Patients in the combination retifanlimab and chemotherapy group achieved a median progression-free survival of 9.3 months compared with 7.4 months among those in the combination placebo and chemotherapy group.
In an interim analysis, the researchers found that the patients who received retifanlimab in combination with chemotherapy achieved about a 6-month improvement in median overall survival vs the patients who received placebo in combination with chemotherapy (29.2 months vs 23.0 months)—with a strong trend toward statistical significance. (HR = 0.70, 95% CI = 0.49–1.01, P = .0273). The overall survival follow-up is ongoing.
Blinded independent central review showed that the patients in the combination retifanlimab and chemotherapy group experienced improvements in the overall response rate (56% vs 44%, 95% CI = 48%–64% vs 36%–52%) and duration of response (14 months vs 7 months, 95% CI = 8.6–22.2 vs 5.6–9.3) compared with the combination placebo and chemotherapy group.
Retifanlimab was generally well-tolerated, and safety was consistent with other chemotherapy plus checkpoint inhibitor regimens. The most common treatment-emergent adverse events in the combination retifanlimab and chemotherapy group were anemia (66.2%), nausea (56.5%) and alopecia (51.3%).
Conclusions
The results built on previously announced topline results, demonstrating that the new study met its primary endpoint by achieving a statistically significant and clinically meaningful improvement in progression-free survival in patients who hadn’t been treated with prior lines of systemic therapy—as assessed by blinded independent central review using RECIST v1.1.
“The POD1UM-303/InterAACT2 trial is [one of] the first and largest phase III trials evaluating a checkpoint inhibitor for the treatment of patients with squamous cell anal carcinoma, a disease with significant medical need. The positive efficacy and safety data presented today at ESMO illustrate the potential of retifanlimab in combination with carboplatin and paclitaxel to become a new standard-of-care treatment for patients with advanced [disease],” highlighted Pablo J. Cagnoni, MD, President and Head of Research and Development at Incyte. “We look forward to working with regulatory authorities to progress the supplemental Biologics License Application for retifanlimab and potentially bring the first-ever PD-1 or PD-L1 antibody to patients with [squamous cell anal carcinoma],” he added.
“I believe the positive results from the POD1UM-303/InterAACT2 trial may provide a long-awaited, new treatment option with retifanlimab in addition to platinum-based chemotherapy for adults with inoperable locally recurrent or metastatic [squamous cell anal carcinoma],” concluded Dr. Rao.
Disclosure: For full disclosures of the study authors, visit cslide.ctimeetingtech.com.
