Gazyva’s GALLIUM Could Be ‘Practice-Changing’ For Follicular Lymphoma
Executive Summary
Genentech’s next-generation anti-CD20 antibody Gazyva bested the Roche subsidiary’s original CD20-targeting therapy Rituxan in first-line follicular lymphoma – a result in the Phase III GALLIUM study that one oncologist viewed as “practice-changing.”
SAN DIEGO – Data from Genentech Inc.’s 1,202-patient Phase III GALLIUM clinical trial in previously untreated follicular lymphoma showed a 34% reduction in the risk of disease progression or death for the Roche subsidiary’s Gazyva (obinutuzumab) compared with the company’s own Rituxan (rituximab) – a result that investigators view as potentially practice-changing.
GALLIUM investigator Robert Marcus, a hematologist at Kings College Hospital in London, said the progression-free survival (PFS) for follicular lymphoma patients enrolled in the study shows that Gazyva in combination with chemotherapy is “markedly superior” to Rituxan plus chemotherapy, which is the standard of care in the first-line induction and maintenance therapy setting. Marcus presented the Phase III results, which will be submitted to global regulatory authorities to support approval in this indication, as part of a Dec. 4 plenary session during the American Society of Hematology (ASH) annual meeting in San Diego.
“The GALLIUM study could be practice-changing in how we treat follicular lymphoma; the GOYA study is not,” John Burke, an oncologist at the Rocky Mountain Treatment Centers in Aurora, Colorado, said in an interview with Scrip. Burke also is affiliated with US Oncology Research and was a clinical investigator on the 1,418-patient Phase III GOYA study for Gazyva plus CHOP chemotherapy versus Rituxan plus CHOP in CD20-positive diffuse large B cell lymphoma (DLBCL), which failed to show a statistically significant improvement in PFS. (Also see "No Hat Trick For Roche's Gazyva In Lymphoma" - Scrip, 18 Jul, 2016.)
Burke said it’s interesting that the anti-CD20 antibody Gazyva worked well in one lymphoma yet didn’t in another, but it’s not clear why the GALLIUM and GOYA studies showed different results versus Rituxan – the foundation of Genentech’s CD20 franchise.
“Diffuse large B cell lymphoma is a different disease than follicular lymphoma and chronic lymphocytic leukemia; it’s an aggressive cancer that grows more quickly,” Burke said. “We may never really know why Gazyva works better in some cancers than in others.”
Gazyva is approved for previously untreated chronic lymphocytic leukemia (CLL) and for follicular lymphoma patients who’ve failed Rituxan therapy. About 14,000 people are diagnosed with follicular lymphoma in the US each year.
“Follicular lymphoma is incurable and each time they relapse they’re harder to treat,” Genentech Vice President of Global Hematology Development Nancy Valente said in an interview with Scrip at ASH. “We want to give them the benefit of the best first therapy.”
Valente said Gazyva gives follicular lymphoma patients a deeper, longer response than Rituxan and Genentech noted that GALLIUM was the first randomized trial to show a benefit versus Rituxan for this slow-growing form of non-Hodgkin lymphoma.
DLBCL, the indication studied in GOYA, appears to be a substantially different disease and that trial’s results will be reviewed to inform the research field, Valente said.
GALLIUM was stopped early due to efficacy on the primary endpoint of progression-free survival, which was statistically significant based on investigator assessments (HR=0.66 and p=0.0012) and independent assessments (HR=0.71 and p=0.0138). Three-year PFS and overall survival (OS) rates – key secondary endpoints in GALLIUM, are illustrated in the table below. (Also see "First-Line Gazyva GALLIUM Success Bolsters Roche's CD20 Franchise" - Scrip, 27 May, 2016.)
|
|
Gazyva plus chemotherapy |
Rituxan plus chemotherapy |
|
PFS at three years (investigator assessment) |
80% |
73.3% |
|
PFS at three years (independent assessment) |
81.9% |
77.9% |
|
OS at three years (HR=0.68; p=0.0094) |
94% |
92.1% |
“The fact that it does improve progression-free survival is potentially important for patients. Patients would like to go longer without progression rather than having to relapse and take a new therapy,” Burke said.
There was some controversy during the ASH plenary session about whether Gazyva’s higher dose contributed to the biologic’s improved efficacy versus Rituxan, but Marcus said during his presentation that no randomized, controlled trials to date have shown a beneficial treatment effect for higher doses of Rituxan.
Patients enrolled in GALLIUM were randomized 1:1 to receive 375mg/m2 of Rituxan on the first day of each cycle of treatment or 1000mg of Gazyva on days one, eight and 15 of the first cycle of treatment with just a single day one-dose for subsequent cycles. Chemotherapy regimens allowed during the trial were eight 21-day cycles of CHOP or CVP chemotherapy or six 28-day cycles of bendamustine. Maintenance therapy for patients who responded to treatment during the first two months was Rituxan or Gazyva every two months for two years.
Genentech described the adverse events observed in GALLIUM as consistent with the safety and tolerability reported in previous studies. The overall rate of grade 3 or higher adverse events was 74.6% in the Gazyva arm and 67.8% in the Rituxan arm. The most common grade 3 or higher side effects – all seen at greater rates in the Gazyva arm – were neutropenia, leukopenia, febrile neutropenia, infusion-related reactions thrombocytopenia, infections and second malignancies. The fatal adverse event rate was 4% for Gazyva and 3.4% for Rituxan.
“The toxicities are higher, but they’re manageable and not particularly clinically important. In terms of cost, Gazyva is not much higher than rituximab, so the downside is quite small,” Burke said.