Retifanlimab plus chemo shows PFS benefit in recurrent or metastatic squamous cell carcinoma of the anal canal

Dr Sheela Rao - The Royal Marsden, London, UK

Anal cancer is a rare cancer but with an increasing incidence and about 40% of patients will have advanced disease. For those patients prognosis is poor and treatment options are limited. So for these patients we have previously established a chemotherapy backbone but this phase III study was to try and determine whether adding an anti-PD-1 monoclonal antibody, retifanlimab, to chemotherapy could improve outcome for these patients.

So this was a phase III study, a global study, recruited between 2020 to 2023. We screened 378 patients and we randomised 308 patients. The randomisation was 1:1 and was between chemotherapy in both arms, so 6 months of carboplatin and paclitaxel, and we randomised for retifanlimab for 12 months versus placebo. Patients in the placebo arm could cross over on progression to single agent retifanlimab. We stratified for PD-L1, we stratified for region and we stratified for locally advanced versus metastatic disease.

Talking to the inclusion, that included patients who had inoperable locally recurrent disease or metastatic disease squamous cell anal cancer and they could not have had previous chemotherapy. They could have had chemoradiation, providing it was 6 months before.

In terms of the primary endpoint, that was progression free survival, but we had an important co-secondary endpoint of overall survival using the alpha spending from the PFS, provided that was positive.  In terms of outcomes what we showed was that we improved the progression free survival, we were aiming for a hazard ratio of 0.67, we actually achieved a hazard ratio of 0.63, so we did show a benefit for the addition of retifanlimab to chemotherapy. We also saw an improvement in overall survival although these data are not yet mature but are very encouraging because we’re already seeing a 6 month improvement in overall survival with the addition of retifanlimab.

It was generally well tolerated, the regimen, there were slightly more side effects with the addition of retifanlimab, as one would expect. So slightly more immune-related adverse events and some more other common grade 3 adverse events but these were all manageable and not concerning and certainly not different to any other checkpoint inhibitor plus chemotherapy regimen.

In summary, this study has demonstrated a benefit for the addition of retifanlimab to carboplatin and paclitaxel. We don’t yet have full subgroup analysis but there does appear to be a benefit at this point. As we’ve met our primary endpoint we’re awaiting further survival data but this is now a new standard of care for patients with advanced anal cancer.