New Rituxan Results as FDA Decision Nears for Lymphoma
There were nearly identical response rates and toxicity with subcutaneous administration of Rituxan (rituximab) and IV administration of the drug to treat follicular lymphoma in the first-line setting, according to results from the phase 3 SABRINA trial that were published in The Lancet Haematology.
In March, the FDA’s Oncologic Drugs Advisory Committee (ODAC) voted unanimously to recommend approval of subcutaneous Rituxan for patients with treatment-naïve follicular lymphoma, treatment-naïve diffuse large B-cell lymphoma, relapsed or refractory low grade or follicular lymphoma and treatment-naïve and relapsed or refractory chronic lymphocytic leukemia.
ODAC based its recommendation on a review of data from five clinical trials, which included the SABRINA study. The FDA is scheduled to issue a final decision by the end of June.
The Overall response rate (ORR) was 84.9 percent in the IV group and 84.4 percent in the subcutaneous group. At the end of the induction phase, patients in the IV group were slightly more likely to have complete response. Point estimates were identical for CR in both groups, and nearly identical for partial response at 52.7 percent in the IV group versus 52.2 percent in the subcutaneous group.
“Our findings from the two-stage SABRINA trial show that subcutaneous rituximab is pharmacokinetically noninferior, and has similar efficacy and a similar safety profile to intravenous rituximab in first-line treatment of follicular lymphoma,” wrote the researchers, led by Andrew Davies, BSc, BM, MRCP, Ph.D., University of Southampton, United Kingdom.
“Both the subcutaneous and intravenous formulations deliver identical rituximab, and the similar overall responses, complete responses, and safety profiles in the two study groups are consistent with the demonstrated Ctrough noninferiority of subcutaneous rituximab relative to intravenous rituximab.”
ORR at the end of maintenance was also similar in both groups, at 78.1 percent in the IV group and 77.9 percent in the subcutaneous group. In the IV group, 56.2 percent had a CR compared with 50.6 percent in the subcutaneous group. At a median follow-up of 37 months, progression-free survival, event-free survival, and overall survival did not differ significantly between groups
From February 2011 to May 2013, researchers enrolled 410 patients into the study at 113 medical centers in 30 countries. Patients were randomly assigned to 375 mg/m² of IV Rituxan (205 patients) or 1400 mg of subcutaneous Rituxan (205 patients), plus six to eight 21-day cycles of CHOP or eight 21-day cycles of CVP, followed by Rituxan maintenance every eight weeks.
Eligible patients had untreated, histologically confirmed, CD20-positive grade 1, 2 or 3a follicular lymphoma; ECOG performance status of 0 to 2; and bidimensionally measurable disease.
As of February 2016, all patients had completed treatment and 195 (48 percent) were in follow-up for progression-free survival. Another 144 (35 percent) were in survival follow-up after progressive disease. Median observation time for all patients was 36.8 months.
Overall, both groups experienced adverse events (AEs) at nearly identical rates, 95 percent in the IV group vs 96 percent in the subcutaneous group. The same was true for incidence of grade 3 or higher AEs, 55 percent versus 56 percent.
The most common AE’s were gastrointestinal disorders (60 percent in the IV group vs 66 percent in the subcutaneous group) and infections and infestations (64 percent in the IV group vs 67 percent in the subcutaneous group).
Neutropenia was the most common grade 3 or higher AE, occurring in 21 percent of the IV group and 26 percent of the subcutaneous group. Seventy-two (34 percent) IV group patients experienced serious AEs versus 73 patients (37 percent) in the subcutaneous group.
Administration-related AEs, mostly grade 1 or 2 local injection-site reactions, were more common in the subcutaneous group at 48 percent versus 35 percent.
Pharmacokinetic analyses at stage 2 induction were in line with stage 1 findings. Stage 1 geometric mean Ctrough was noninferior for subcutaneous Rituxan compared with IV administration. Geometric mean ratio was 1.5 (90 percent CI, 1.3-1.7) and the coefficient of variation was similar in both arms (43.6 percent for subcutaneous administration vs 42.5 percent for IV). Researchers also said that pharmacokinetic findings were similar in both groups during the maintenance phase of stage 2.