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The addition of the PD-1 inhibitor retifanlimab to standard-of-care chemotherapy improved response rate and progression-free survival in patients with refractory squamous cell carcinoma of the anal canal (SCAC), the first results of the phase 3 POD1UM-303/InterAACT 2 study demonstrated.
Anal cancer is an orphan disease but its incidence is increasing by ~3% per year, mainly due to endemic HPV, the causative agent for most anogenital cancers [1]. Relapse after primary chemoradiation is common, prognosis is poor, and quality-of-life is greatly diminished for patients who relapse or who have de novo metastatic disease [2].
The InterAACT phase 2 study established carboplatin-paclitaxel as first-line treatment of advanced anal cancer and the PD-1 inhibitor retifanlimab showed anti-tumour activity in platinum-refractory SCAC [3,4]. The phase 3 POD1UM-303/InterAACT 2 study (NCT04472429) evaluated first-line therapy of retifanlimab in combination with carboplatin-paclitaxel in patients with locally advanced or metastatic SCAC.
The study enrolled 308 participants who were randomised 1:1 to receive retifanlimab plus carboplatin-paclitaxel or placebo plus carboplatin-paclitaxel. Participants receiving placebo were allowed to crossover after confirmed progression of disease. The primary endpoint was progression-free survival (PFS). Dr. Sheela Rao (Royal Marsden, UK) presented the results [5].
After a median follow-up of 7.6 months, the primary endpoint was met. Median PFS was 9.3 months in the retifanlimab arm versus 7.4 months in the placebo arm (HR 0.63; 95% CI 0.47–0.84; P=0.0006). Overall survival data is not yet mature but shows a strong trend to benefit of retifanlimab. Retifanlimab also favoured response rates (overall response rate 56% vs 44%; complete response 22% vs 14%), and median duration of response (14.0 vs 7.2 months).
Safety was consistent with prior phase 2 data, meaning more immune-related adverse events were seen in the retifanlimab arm, as expected.
“This study demonstrates encouraging efficacy and a favourable benefit/risk ratio for retifanlimab plus standard-of-care chemotherapy as first-line treatment of locally recurrent/metastatic SCAC and suggests a new standard-of-care,” concluded Dr. Rao.
Medical writing support was provided by Marten Dooper.
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