The approval is based on the phase 3 GADOLIN study, in which Gazyva plus bendamustine followed by Gazyva alone reduced the risk of disease progression by 52 percent in patients with follicular lymphoma.
The FDA approved Gazyva (obinutuzumab) plus bendamustine followed by Gazyva alone for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a Rituxan (rituximab)-containing regimen, according to Genentech, the manufacturer of the anti-CD20 agent.
The approval is based on the phase 3 GADOLIN study, in which Gazyva plus bendamustine followed by Gazyva monotherapy reduced the risk of disease progression by 52 percent compared with bendamustine alone in patients with follicular lymphoma who progressed on Rituxan-based therapy.
"People with follicular lymphoma whose disease returns or worsens despite treatment with a Rituxan-containing regimen need more options because the disease becomes more difficult to treat each time it comes back," said Sandra Horning, chief medical officer and head of Global Product Development at Genentech. "Gazyva plus bendamustine provides a new treatment option that can be used after relapse to significantly reduce the risk of progression or death."
The multicenter, open-label, phase 3 GADOLIN study involved 413 patients with Rituxan-refractory indolent non-Hodgkin lymphoma, the most common being follicular lymphoma (321 patients). Patients were considered Rituxan-refractory if they did not respond to either Rituxan monotherapy or Rituxan in combination with chemotherapy, or had relapsed within six months of completion of the last dose of a Rituxan-based regimen (Rituxan monotherapy or Rituxan plus chemotherapy).
Patients in the experimental arm (155 patients) received bendamustine (90 mg/m2 IV on days 2 and 3 of cycle 1, and days 1 and 2 of cycles 2 to 6) plus six cycles of Gazyva (1000 mg IV on days 1, 8, and 15 of cycle 1, and day 1 of cycles 2 to 6) followed by Gazyva every two months until disease progression for a maximum of two years. In the comparator group (166 patients), patients received six cycles of bendamustine monotherapy. The cycle length for both treatment arms was 28 days.
Clinical characteristics across both arms of the study were comparable: median patient age was 63 years, with a median of two prior lines of therapy (ranging from 1 to 10); approximately four months had elapsed since their last treatment. More than 90 percent of patients in each arm were refractory to their last treatment.
The primary endpoint of the study was progression-free survival (PFS). Secondary outcome measures included overall survival (OS), response and safety.
The median PFS, as determined by an independent panel, was not reached in the Gazyva arm versus 13.8 months in the control arm. By investigator assessment, the median PFS with Gazyva was 29.2 months versus 13.7 months with bendamustine alone.
At a median follow-up of 24.1 months, the risk of death was reduced by 38 percent with the Gazyva regimen compared with bendamustine alone, according to Genentech. Neither study arm has reached median OS.
The best overall response (BOR) rate for the Gazyva cohort was 78.7 percent, including complete (CR) and partial response (PR) rates of 15.5 percent and 63.2 percent, respectively. The BOR was 74.7 percent for the control arm, with a CR rate of 18.7 percent and a PR rate of 56 percent. The median duration of response was not reached for the Gazyva arm versus 11.6 months with bendamustine alone.
The most frequently reported adverse events (AEs) in the Gazyva arm were infusion reactions (69 percent), low white blood cell counts (35 percent), nausea (54 percent), fatigue (39 percent), cough (26 percent), diarrhea (27 percent), constipation (19 percent), fever (18 percent), low platelet counts (15 percent), vomiting (22 percent), upper respiratory tract infection (13 percent), decreased appetite (18 percent), joint or muscle pain (12 percent), sinusitis (12 percent), low red blood cell counts (12 percent), general weakness (11 percent) and urinary tract infection (10 percent).
Low white blood cell counts (33 percent), infusion reactions (11 percent) and low platelet counts (10 percent), were the most common grade 3/4 AEs observed in patients receiving Gazyva.
The most common serious AEs (greater than 2 percent) included febrile neutropenia, neutropenia, infusion related reactions, sepsis, pneumonia and pyrexia.
Gazyva is also approved by the FDA for use in combination with chlorambucil as a first-line treatment for patients with chronic lymphocytic leukemia.