In a French noncomparative phase II study (SCARCE C17-02 PRODIGE 60) reported in The Lancet Oncology, Stefano Kim, MD, and colleagues found that the addition of atezolizumab to modified docetaxel, cisplatin, and fluorouracil (mDCF) did not meet the 12-month progression-free survival primary endpoint in the first-line treatment of patients with advanced anal squamous cell carcinoma. Benefit was observed in patients with PD-L1 combined positive score (CPS) of ≥ 5.

Stefano Kim, MD

Study Details

In the open-label multicenter trial, 97 evaluable patients were randomly assigned 2:1 to receive atezolizumab at 800 mg every 2 weeks for up to 1 year plus mDCF (n = 64) or mDCF alone (n = 33). mDCF consisted of eight cycles of docetaxel at 40 mg/m² and cisplatin at 40 mg/m² on day 1 and fluorouracil at 1,200 mg/m² per day for 2 days every 2 weeks. The primary endpoint was investigator-assessed 12-month progression-free survival in the atezolizumab/mDCF group; the primary endpoint was considered met if the lower bound of the 90% confidence interval exceeded 35%.

12-Month Progression-Free Survival

Median follow-up was 26.5 months (95% confidence interval [CI] = 24.8–28.4 months). Progression-free survival at 12 months in the atezolizumab/mDCF group was 45% (90% CI = 35%–55%), with the endpoint not being met. Progression-free survival at 12 months in the mDCF group was 43% (90% CI = 29%–58%). Among 10 patients in each group with PD-L1 CPS ≥ 5, 12-month progression-free survival was 70% (95% CI = 47%–100%) in the atezolizumab/mDCF group and 40% (95% CI = 19%–85%) in the mDCF group (P for interaction = .051).

Median progression-free survival was 9.4 months (90% CI = 7.4–13.5 months) in the atezolizumab/mDCF group and 8.7 months (90% CI = 6.8–14.7 months) in the mDCF group. Median overall survival was 24.8 months (95% CI = 19.0 months to not evaluable) and not evaluable (95% CI = 25.3 months to not evaluable).

Adverse Events

Grade ≥ 3 adverse events occurred in 61% of patients in the atezolizumab/mDCF group and 42% of the mDCF group, with the most common grade 3 or 4 events being neutropenia (14% and 15%), anemia (14% and 3%), fatigue (5% and 12%), and diarrhea (11% and 3%). Serious adverse events occurred in 25% and 12% of patients—those considered related to atezolizumab occurred in 14% and included infusion-related reaction (5%); infection (3%); and colitis, acute kidney injury, sarcoidosis, and decreased platelets in one patient each. No treatment-related deaths were reported.

The investigators concluded, “Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 CPS of 5 or greater now needs to be confirmed in future studies.”

Dr. Kim, of the Department of Medical Oncology, University Hospital of Besançon, Besançon, France, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was supported by GERCOR and Roche. For full disclosures of the study authors, visit thelancet.com.