Atezolizumab plus modified DCF (docetaxel, cisplatin, and 5-fluorouracil) as first-line treatment for metastatic or locally advanced squamous cell anal carcinoma: A SCARCE-PRODIGE 60 randomized phase II study.

3508 Background: Modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) regimen is one of the first-line standard regimens for the treatment of metastatic or unresectable locally advanced recurrent squamous cell carcinoma of the anus (SCCA) after demonstrating an improved efficacy (12-month PFS of 47%) in the Epitopes-HPV02 trial. Antibodies targeting the checkpoint inhibitor (CKI) programmed cell death protein-1 have been shown to be effective as monotherapy in advanced SCCA, refractory to chemotherapy. The aim of this study was to evaluate the combination of atezolizumab and mDCF as first-line treatment. Methods: This is a 2:1 randomized, non-comparative, multicenter, phase II study (NCT03519295) with an experimental arm (Arm A, mDCF plus atezolizumab) and standard arm (Arm B, mDCF). Patients with chemo-naive SCCA, metastatic or unresectable locally advanced recurrence were eligible. In Arm A, survival probabilities for null and alternative hypotheses for the primary endpoint 12-months PFS rate were 35 and 50%, respectively. Using one-arm non-parametric survival with unilateral alpha type I error of 5% and a statistical power of 81%, 64 patients in 2 years with 1 year of follow-up need to be randomized in Arm A. The lowest expected critical value would be a PFS rate of 46% to reject H0. In both arms, 8 cycles of mDCF were administered. In Arm A, patients received a fixed dose of atezolizumab (800 mg every 2 weeks) before each mDCF cycle and were followed up to 1 year. Results: Ninety-sevenevaluable patients were enrolled, 64 in Arm A and 33 in Arm B. The median age was 64.1 years, 73.2% were women, and 78,3% had a metastatic disease. More patients in Arm A had an ECOG-PS 1 (42.2% vs 27.3%), liver involvement (56.9% vs 48%), and an extensive local recurrence (23.5% vs 8%). The median follow-up was 22.3 months (95% CI 20.8-24.8).The 12-month PFS rate was 44.2% (90% CI 33.7-54.2) and 43.2% (90% CI 28.5-57.0) in Arm A and Arm B, respectively, and the 12-month OS rate was 77.7% (95% CI 68.1-88.7) and 80.8% (95% CI 68.1-95.9).The objective response rate was 74.6% and 78.1% in Arm A and Arm B, respectively. A high dose-intensity and a good safety profile were observed in both arms. Grade ≥3 toxicities were observed in 59.0% and 36.4% of patients in Arm A and Arm B, respectively, with no toxic death. Conclusions: The results of SCARCE trial are consistent with previous results of mDCF, with high efficacy and safety at first-line in patients with advanced SCCA. However, the concomitant addition of CKI did not make a significant clinical impact at 12 months. Updated results will be presented. Clinical trial information: NCT03519295.