U.S. Food and drug administration approval: obinutuzumab in combination with chlorambucil for the treatment of previously untreated chronic lymphocytic leukemia.
On November 1, 2013, the U.S. Food and Drug Administration (FDA) approved obinutuzumab (GAZYVA; Genentech, Inc.), a CD20-directed cytolytic antibody, for use in combination with chlorambucil for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). In stage 1 of the trial supporting approval, patients with previously untreated CD20-positive CLL were randomly allocated (2:2:1) to obinutuzumab + chlorambucil (GClb, n = 238), rituximab + chlorambucil (RClb, n = 233), or chlorambucil alone (Clb, n = 118). The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall response rate (ORR). Only the comparison of GClb to Clb was relevant to this approval and is described herein. A clinically meaningful and statistically significant improvement in PFS with medians of 23.0 and 11.1 months was observed in the GClb and Clb arms, respectively (HR, 0.16; 95% CI, 0.11-0.24; P < 0.0001, log-rank test). The ORRs were 75.9% and 32.1% in the GClb and Clb arms, respectively, and the complete response rates were 27.8% and 0.9% in the GClb and Clb arms, respectively. The most common adverse reactions (≥10%) reported in the GClb arm were infusion reactions, neutropenia, thrombocytopenia, anemia, pyrexia, cough, and musculoskeletal disorders. Obinutuzumab was the first Breakthrough Therapy-designated drug to receive FDA approval.
Office of Hematology and Oncology Products, Office of New Drugs; Hyon.Lee@fda.hhs.gov.
Hyon-Zu
HZ
Lee
Office of Hematology and Oncology Products, Office of New Drugs;
Barry W
BW
Miller
Office of Hematology and Oncology Products, Office of New Drugs;
Virginia E
VE
Kwitkowski
Office of Hematology and Oncology Products, Office of New Drugs;
Stacey
S
Ricci
Office of Hematology and Oncology Products, Office of New Drugs;
Pedro
P
DelValle
Office of Hematology and Oncology Products, Office of New Drugs;
Haleh
H
Saber
Office of Clinical Pharmacology;
Joseph
J
Grillo
Office of Clinical Pharmacology;
Julie
J
Bullock
Office of Clinical Pharmacology;
Jeffry
J
Florian
Office of Clinical Pharmacology;
Nitin
N
Mehrotra
Office of Biostatistics;
Chia-Wen
CW
Ko
Office of Biostatistics;
Lei
L
Nie
Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Marjorie
M
Shapiro
Office of Biotechnology Products, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland.
Mate
M
Tolnay
Office of Hematology and Oncology Products, Office of New Drugs;
Robert C
RC
Kane
Office of Hematology and Oncology Products, Office of New Drugs;
Edvardas
E
Kaminskas
Office of Hematology and Oncology Products, Office of New Drugs;
Robert
R
Justice
Office of Hematology and Oncology Products, Office of New Drugs;
Ann T
AT
Farrell
Office of Hematology and Oncology Products, Office of New Drugs;
Richard
R
Pazdur
D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002699:Chlorambucil / Q000008:administration & dosage; D017277:Drug Approval; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D011379:Prognosis; D015996:Survival Rate; D014481:United States; D014486:United States Food and Drug Administration
D061067:Antibodies, Monoclonal, Humanized; D002699:Chlorambucil; C543332:obinutuzumab