As reported in The Lancet Oncology by Fizazi et al, the phase III CheckMate 7DX trial showed no progression-free or overall survival benefit with the addition of nivolumab to docetaxel in patients with androgen receptor pathway inhibitor (ARPI)–pretreated and chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).
Study Details
In the double-blind trial, 1,030 patients from sites in 27 countries were randomly assigned between March 2020 and August 2022 to receive nivolumab at 360 mg (n = 514) or placebo (n = 516) plus docetaxel at 75 mg/m² every 3 weeks for up to 10 doses, followed by nivolumab at 480 mg or placebo every 4 weeks. The primary endpoints of the study were radiographic progression–free survival on blinded independent central review and overall survival.
Key Findings
Median follow-up was 17.2 months (interquartile range = 13.2–22.0 months).
Median radiographic progression–free survival was 9.4 months (95% confidence interval [CI] = 8.5–10.3 months) in the nivolumab group vs 8.7 months (95% CI = 8.4–10.0 months) in the control group (hazard ratio [HR] = 0.96, 99% CI = 0.77–1.19, P = .59). Subsequent systemic anticancer therapy was received by 46% of patients in the nivolumab group vs 52% of the control group, most commonly chemotherapy (27% vs 31%) and ARPIs (14% vs 16%).
Median overall survival was 18.7 months (95% CI = 17.0–21.0 months) in the nivolumab group vs 18.9 months (95% CI = 17.3–22.0 months) in the control group (HR = 1.09, 99.41% CI = 0.84–1.43, P = .36).
Grade 3 to 4 treatment-related adverse events occurred in 44% of patients in the nivolumab group vs 37% of the control group, most commonly neutropenia (7% vs 10%) and decreased neutrophil count (8% vs 8%) in both groups. Any-grade treatment-related serious adverse events occurred in 21% vs 15% of patients. Death was attributed to study drug toxicity by investigators in 12 patients in the nivolumab group (due to sepsis in three patients, and Guillain-Barré syndrome, diverticulitis, myocarditis, liver injury, peritonitis, pneumonitis, pneumonia, diarrhea, and unknown cause in one each) and in one patient in the control group (due to pneumocystis).
The investigators concluded: “Nivolumab plus docetaxel did not improve progression-free survival or overall survival vs placebo plus docetaxel in patients with ARPI-pretreated, chemotherapy-naive mCRPC. These findings do not support the use of combinations of anti-PD-1 immune checkpoint inhibitors and docetaxel in the treatment of unselected populations of patients with ARPI-pretreated, chemotherapy-naive mCRPC.”
Karim Fizazi, MD, of Gustave Roussy and Centre Oscar Lambret, University of Paris Saclay, Villejuif, France, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by Bristol Myers Squibb. For full disclosures of all study authors, visit thelancet.com.
