Retifanlimab boosts survival in patients with anal cancer

The addition of the PD-1 inhibitor retifanlimab to standard-of-care chemotherapy improved response rate and progression-free survival (PFS) 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. Dr Sheela Rao (Royal Marsden, UK) presented the results [5].

The study randomised 308 participants 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 PFS.

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; see Figure). Overall survival data is not yet mature but shows a strong trend towards 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).

Figure: Median PFS in POD1UM-303/InterAACT 2 [5]



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.

1. Gondal TA, et al. Curr Oncol. 2023;30:3232-3250.
2. Rao S, et al. Ann Oncol. 2021;32:1087-1100.
3. Rao S, et al. J Clin Oncol. 2020;38:2510-2518.
4. Rao S, et al. ESMO Open. 2022;7:100529.
5. Rao S, et al. POD1UM-303/InterAACT 2: Phase III study of retifanlimab with carboplatin-paclitaxel (c-p) in patients (Pts) with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC) not previously treated with systemic chemotherapy (Chemo). Abstract LBA2, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024