Androgen receptor pathway inhibitors (ARPIs) and docetaxel are established standards of care for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the efficacy and safety of adding nivolumab to docetaxel versus docetaxel alone in ARPI-pretreated, chemotherapy-naive mCRPC.
CheckMate 7DX was a double-blind, randomised, phase 3 trial that enrolled adult patients (aged ≥18 years) with histologically confirmed, ARPI-pretreated, and chemotherapy-naive mCRPC at 291 hospitals and cancer centres across 27 countries. Patients had documented progression within 6 months of screening and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to nivolumab (360 mg), or equivalent placebo, and docetaxel (75 mg/m2) intravenously every 3 weeks for up to ten doses, followed by nivolumab (480 mg) or equivalent placebo every 4 weeks. Randomisation, stratified by previous ARPI therapy and visceral disease, was done using interactive response technology in permuted blocks with a block size of six. Patients, investigators, and the trial sponsor were masked to individual patient treatment assignment. The primary endpoints were radiographic progression-free survival by blinded independent central review and overall survival, assessed in all randomly assigned patients. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04100018, and is completed.
Between March 11, 2020, and Aug 2, 2022, 1414 patients were screened for eligibility, 1030 of whom were randomly assigned to nivolumab plus docetaxel (n=514) or placebo plus docetaxel (n=516). All participants were male, median age was 70 years (range 34-91), 662 (64%) were White, 240 (23%) were Asian, and 35 (3%) were Black or African American. With a median follow-up of 17·2 months (IQR 13·2-22·0), median radiographic progression-free survival was 9·4 months (95% CI 8·5-10·3) in the nivolumab plus docetaxel group versus 8·7 months (95% CI 8·4-10·0) in the placebo plus docetaxel group (hazard ratio [HR] 0·96 [99% CI 0·77-1·19]; p=0·59) and median overall survival was 18·7 months (95% CI 17·0-21·0) versus 18·9 months (95% CI 17·3-22·0, HR 1·09 [99·41% CI 0·84-1·43]; p=0·36). Grade 3-4 treatment-related adverse events occurred in 223 (44%) of 510 patients in the nivolumab plus docetaxel group and 187 (37%) of 510 in the placebo plus docetaxel group. The most common grade 3-4 events in both treatment groups were neutropenia (37 [7%] in the nivolumab plus docetaxel group and 50 [10%] in the placebo plus docetaxel group) and decreased neutrophil count (41 [8%] and 39 [8%]). Any-grade treatment-related serious adverse events occurred in 107 (21%) patients in the nivolumab plus docetaxel group and 77 (15%) in the placebo plus docetaxel group. 12 deaths were attributed to nivolumab plus docetaxel (three due to sepsis; one each due to Guillain-Barré syndrome, diverticulitis, myocarditis, liver injury, peritonitis, pneumonitis, pneumonia, and diarrhoea; and one due to unknown causes) and one was attributed to placebo plus docetaxel (due to pneumocystis).
Nivolumab plus docetaxel did not improve progression-free survival or overall survival versus 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.
Bristol Myers Squibb.
The Lancet. Oncology. 2026 Jan [Epub]
Karim Fizazi, Fred Saad, Teresa Alonso-Gordoa, Bogdan Żurawski, Philippe Barthélémy, Eric Voog, Hernán Javier Cutuli, Tomas Buchler, Dingwei Ye, Daniel Castellano, Mariusz Kwiatkowski, Cagatay Arslan, Martin Richardet, Constantine Alifrangis, Jeffrey C Goh, Karina Vianna, Weiqing Han, Koji Hatano, Tilmann Todenhöfer, Margitta Retz, Abhinav Srivastava, Chelsea Jin, Saurabh Gupta, Gilda Trandafirescu, Arancha Campos, Chung-Wei Lee, Maximiliano van Kooten Losio, Sumit K Subudhi
Department of Cancer Medicine, Gustave Roussy and Centre Oscar Lambret, University of Paris Saclay, Villejuif, France. Electronic address: ., Department of Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, QC, Canada., Medical Oncology Department, University Hospital Ramón y Cajal, Madrid, Spain., Department of Outpatient Chemotherapy, Prof Franciszek Łukaszczyk Oncology Centre, Bydgoszcz, Poland., Department of Medical Oncology, University Hospital Strasbourg, Strasbourg, France., Department of Medical Oncology, Clinique Victor Hugo, Centre Jean Bernard, Le Mans, France., Department of Medical Oncology, Hospital Sirio Libanés, Buenos Aires, Argentina., Department of Oncology, First Faculty of Medicine, Charles University and Thomayer University Hospital, Prague, Czech Republic., Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai, China., Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain., Department of Chemotherapy, Szpital Wojewódzki im Mikołaja Kopernika w Koszalinie, Koszalin, Poland., Department of Medical Oncology, Faculty of Medicine, İzmir University of Economics and Medical Point Hospital, Izmir, Turkey., Department of Oncology, Fundación Richardet Longo, Instituto Oncológico de Córdoba, Cordoba, Argentina., Division of Cancer, University College London Hospitals NHS Trust, London, UK., Medical Oncology, ICON Research, South Brisbane and Queensland University of Technology, Brisbane, QLD, Australia., CIONC-Centro Integrado de Oncologia de Curitiba, Mercês, Curitiba, Brazil., Department of Urology Surgery, Hunan Cancer Hospital, Changsha, China., Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan., Clinical Trial Unit, Studienpraxis Urologie, Nuertingen, Germany., Department of Urology, Rechts der Isar Medical Center, Technical University Munich, Munich, Germany., Department of Biostatistics, Bristol Myers Squibb, Princeton, NJ, USA., Global Biometrics and Data Sciences, Bristol Myers Squibb, Princeton, NJ, USA., Department of Translational Medicine, Bristol Myers Squibb, Princeton, NJ, USA., Department of Oncology Clinical Development, Bristol Myers Squibb, Princeton, NJ, USA., Department of Oncology Clinical Science, Bristol Myers Squibb, Princeton, NJ, USA., Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.