Atezolizumab Added to Chemotherapy Fails to Improve Outcomes in Anal Cancer

Metastatic anal cancer can be treated with the combination of carboplatin and paclitaxel. Recent phase 2 data support the use of docetaxel, cisplatin and infusional 5-FU (DCF) as an alternative first-line regimen. Immune checkpoint inhibitors have a modest degree of activity in anal cancer and are supported for use in later-line therapy.

Investigators in France now report results of an industry-supported, open-label, phase 2 trial evaluating the addition of atezolizumab to first-line chemotherapy with a modified schedule of DCF (mDCF). Patients with metastatic anal cancer were randomized to receive mDCF (docetaxel 40 mg/m² and cisplatin 40 mg/m² for 1 day and 5-FU 1200 mg/m² per day for 2 days every 2 weeks) either alone or combined with atezolizumab (800 mg cycled every 2 weeks). Of the 97 patients, 73% were female; 41% had synchronous metastases and 37% had metachronous metastases; 51% had received prior chemoradiotherapy; and nearly half had liver and distant lymph node metastases.

The primary endpoint of progression-free survival (PFS) at 12 months was not improved with the addition of atezolizumab compared with chemotherapy alone (45% vs. 43%). There was also no difference in median PFS (9.4 vs. 8.7 months, respectively), 12-month overall survival (77% vs. 81%), or response rate (75% vs. 78%). In the subset of patients with combined positive PD-L1 scores (CPS) ≥5%, 12-month PFS was higher with atezolizumab than with chemotherapy alone. Rates of grade 3/4 serious adverse events were higher with atezolizumab compared with chemotherapy alone (61% vs. 42%).