OREANDA-NEWS. Roche announced today that the European Commission has approved Gazyvaro® (obinutuzumab) in combination with bendamustine chemotherapy followed by Gazyvaro maintenance in people with follicular lymphoma who did not respond or who progressed during or up to six months after treatment with MabThera® (rituximab) or a MabThera-containing regimen.

The approval is based on results from the pivotal phase III GADOLIN study which showed that Gazyva/Gazyvaro plus bendamustine, followed by Gazyva/Gazyvaro alone resulted in a 52 percent reduction (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001) in the risk of disease worsening or death (progression-free survival, PFS), compared to bendamustine alone, as evaluated by an independent review committee (IRC). As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001). People who received the Gazyva/Gazyvaro regimen also showed a 38 percent reduction (HR=0.62, 95 percent CI 0.39-0.98) in the risk of death (OS) compared to those who received bendamustine alone.

“Today’s approval is a significant milestone in the treatment of people with follicular lymphoma in Europe,” said Sandra Horning, MD, Chief Medical Officer and Head of Global Product Development. “For those who fail to achieve durable disease control with MabThera-based treatment, Gazyvaro plus bendamustine is an important new treatment option that has been shown to reduce the risk of disease progression or death by more than half.”

Every day, more than 50 people in Europe are diagnosed with follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin lymphoma (NHL).1,2 During initial therapy, response rates to MabThera-based treatment, the current standard of care, are greater than 90 percent, but there is no cure and people will eventually relapse.3,4 The disease becomes more difficult to treat at each relapse, and if a patient does not respond or relapses during or within 6 months of MabThera -containing treatment, they will likely need a different treatment. These people often have a poor prognosis and few treatment options.5

With this approval, Gazyvaro is now approved in Europe to treat two common types of blood cancer. Gazyvaro was previously approved in combination with chlorambucil for people with previously untreated chronic lymphocytic leukaemia (CLL) and comorbidities that make them unsuitable for full-dose fludarabine based therapy. That approval was based on data from the pivotal CLL11 study, where the combination of Gazyva/Gazyvaro plus chlorambucil showed superior efficacy when compared head-to-head with MabThera/Rituxan plus chlorambucil and chlorambucil alone.

Gazyvaro is marketed as Gazyva outside of the EU and Switzerland. As announced in February this year, Gazyva received approval by the US Food and Drug Administration in combination with bendamustine followed by Gazyva alone as a treatment for people with follicular lymphoma who did not respond to a Rituxan-containing regimen, or whose follicular lymphoma returned after such treatment, based on the results of the GADOLIN study.

About the GADOLIN study

GADOLIN (NCT01059630; GA04753g) is a phase III open-label, multicentre, randomised two-arm study evaluating Gazyva/Gazyvaro plus bendamustine followed by Gazyva/Gazyvaro alone until disease progression or for up to two years compared to bendamustine alone. GADOLIN included 396 patients with indolent (slow-growing) non-Hodgkin lymphoma (NHL), including 321 patients with follicular lymphoma, whose disease progressed during or within six months of prior MabThera/Rituxan-based therapy. The primary endpoint of the study is progression-free survival (PFS) as assessed by an independent review committee (IRC), with secondary endpoints including PFS as assessed by investigator review, best overall response (BOR), complete response (CR), partial response (PR), duration of response, overall survival (OS) and safety profile. Results in follicular lymphoma showed:

  • The Gazyva/Gazyvaro regimen improved PFS compared to bendamustine alone, as assessed by IRC (HR=0.48, 95 percent CI 0.34-0.68, p<0.0001). Median PFS was not reached in those receiving the Gazyva/Gazyvaro regimen versus 13.8 months in those receiving bendamustine alone.
  • Investigator-assessed PFS was consistent with IRC-assessed PFS. As assessed by investigator review, median PFS with the Gazyva/Gazyvaro regimen was more than double that with bendamustine alone (29.2 months vs. 13.7 months; HR=0.48, 95 percent CI 0.35-0.67, p<0.0001).
  • The Gazyva/Gazyvaro regimen reduced the risk of death (OS) by 38 percent compared to bendamustine alone based on a post-hoc analysis eight months after the primary analysis (HR=0.62, 95 percent CI 0.39-0.98). The median OS has not yet been reached in either study arm.
  • The most common Grade 3-4 adverse events that occurred more often (at least 2 percent or greater) in those receiving the Gazyva/Gazyvaro regimen compared to those receiving bendamustine alone were low white blood cell count (33 percent vs. 26 percent), infusion-related reactions (11 percent vs. 6 percent) and urinary tract infection (3 percent vs. 0 percent), respectively.