Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.

1st Department of Medicine 1st Faculty of Medicine Charles University General Hospital Prague Czech Republic

3rd Medical Department With Hematology Medical Oncology Rheumatology and Infectiology Paracelsus Medical University Salzburg Austria

4th Department of Internal Medicine Haematology Faculty of Medicine in Hradec Králové University Hospital and Charles University Prague Hradec Králové Czech Republic

Alfred Health and Monash University Melbourne VIC Australia

BeiGene USA Inc San Mateo CA

Cancer Cluster Salzburg Salzburg Austria

Concord Repatriation General Hospital Concord NSW Australia

Copernicus Memorial Hospital Medical University of Łódź Łódź Poland

Dana Farber Cancer Institute Boston MA

Department of Chemotherapy of Hemoblastosis Blokhin Russian Cancer Research Center Moscow Russia

Department of Haematology Waitemata District Health Board Takapuna New Zealand

Department of Hematology and Cancer Prevention School of Public Health Silesian Medical University Katowice Poland

Department of Hematology Azienda Socio Sanitaria Territoriali Grande Ospedale Metropolitano Niguarda Milan Italy

Department of Hematology Copernicus Regional Oncology Centre Gdansk Poland

Department of Hematology Karolinska University Hospital Solna Stockholm Sweden

Experimental Hematooncology Department Medical University of Lublin Lublin Poland

Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Fred Hutchinson Cancer Center University of Washington Seattle WA

Haematology Leeds Teaching Hospitals NHS Trust Leeds United Kingdom

Hematologic Malignancies and Cellular Therapy Duke University School of Medicine Durham NC

Hematology Department Centre Hospitalier du Mans Le Mans France

Hematology Department St John's Cancer Centre Lublin Poland

Hematology Unit Santa Maria delle Croci Hospital Ravenna Italy

Hôpital de Pontchaillou Rennes France

IRCCS Ospedale San Raffaele Milano Italy

Lymphoma Research Group School of Clinical Sciences at Monash Health Monash University Clayton VIC Australia

Maria Skłodowska Curie National Research Institute of Oncology Kraków Poland

Peninsula Health and Peninsula Private Hospital Frankston Melbourne VIC Australia

Salzburg Cancer Research Institute Center for Clinical Cancer and Immunology Trials Salzburg Austria

Siteman Cancer Center Washington University School of Medicine St Louis MO

Tennessee Oncology OneOncology Nashville TN

The 1st Affiliated Hospital of Nanjing Medical University Jiangsu Province Hospital Nanjing China

Unidad de Citogenetica Molecular Servicio de Hematología Hospital Universitario Puerta de Hierro Majadahonda Madrid Spain

Università Vita Salute San Raffaele Milano Italy

University of Sydney Sydney NSW Australia

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ClinicalTrials.gov
NCT03336333