Details of the study that led to recent approval of Genentech’s Gazyva for the treatment of chronic lymphocytic leukemia (CLL) are now available. Goede et al published their results in the New England Journal of Medicine.
The study was a massive undertaking involving 781 patients from 189 treatment centers in 26 countries who were randomly assigned to one of the following treatment groups on a 1:2:2 basis: Leukeran (chlorambucil) alone; Gazyva + Leukeran (obinutuzumab + chlorambucil); or Rituxan + Leukeran (rituximab + chlorambucil) and each patient received treatment for six 28-day cycles.
What was unique about the patient selection was that all patients had to have a confirmed co-existing condition. Since most CLL patients are older and have coexisting conditions, this design hopefully better reflects real world conditions when treating patients with CLL. Common coexisting conditions included cardiac problems, hypertension, respiratory problems etc. Most patients (82%) had more than three coexisting conditions, and 27% had at least one coexisting condition that was not well controlled at baseline. The study was also unique in that it compared not just the drug being tested (Gazyva combination) to a standard chemotherapy control (Leukeran alone) but also compared the drug to anoher drug that also targets CD20 (Rituxan combination).
Median progressive free survival (PFS) in the three treatment groups were:
Median PFS values for both combination treatment groups were found to be significantly different to the median PFS for the Leureran alone group. In a comparison between the two combination groups, the Gazyva + Leukeren group was statistically superior to the Rituxan + Leukeran group in measurements of response rate and probability of progressive free survival.
The improvement in efficacy however needs to be balanced with safety. Percentage of patients with any grade 3 or higher events were higher in the Gazyva comination group [70-73% (Gazyva + Leukeran), 55-56% (Rituxan + Leukeran), and 50% (Leukeran alone)]. However, the percentage of patients who died because of an adverse event was also lower in the Gazyva + Leukeran group (4%) than in the Rituxan + Leukeran and Leukeran alone groups (6% and 9%, respectively).
In their discussion of the results, the authors noted “Most enrolled patients were older than 70 years of age and had clinically meaningful health problems in addition to CLL. Although elderly patients with coexisting conditions represent the majority of patients with CLL, they have been underrepresented in prior clinical trials…….Our study shows that the combination of an anti-CD20 antibody with chlorambucil results in a better response and prolongation of progression-free survival in these patients.”
CLL is one of the more common rare cancers afflicting the elderly. CLL symptoms and progression can vary greatly among patients with long periods of stability or even regression. There is currently no cure for CLL but there are numerous treatment options are available to delay progression (eg, Rituxan and Gazyva) but treatment course will be highly dependent on the individual’s health and the disease severity/progression.
Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. New Engl J Med. 2014 [Epub ahead of print]. DOI:10.1056/NEJMoa1313984
Source: Rare Disease Report