Treatment with GP2013-CVP met the primary endpoint of equivalence in overall response rate (ORR) compared to rituximab-CVP in a confirmatory phase III trial that was conducted in patients with previously untreated, advanced-stage follicular lymphoma, ASSIST-FL researchers reported at ESMO 2017, the Annual Congress of the European Society for Medical Oncology in Madrid, Spain.
Rituximab is a monoclonal IgG-1 antibody targeting the CD20 antigen on B cells. Therituximab biosimilar, GP2013, was developed according to biosimilar development guidelines and had previously demonstrated equivalence in rheumatoid arthritis in a clinical trial.
Wojciech Jurczak of the Department of Haematology, Jagiellonian University Kraków in Kraków, Poland and colleagues conducted this confirmatory phase III, double-blind, randomised, controlled trial in patients with previously untreated, advanced-stage follicular lymphoma.
In the trial (NCT01419665), GP2013-CVP regimen was compared to rituximab(R)-CVP in terms of efficacy, safety, pharmacokinetics (PK) and pharmacodynamics (PD). The primary efficacy endpoint was equivalence in ORR defined by a 95% confidence interval [CI] with a margin of ±12% standard deviation. Secondary endpoints were non-powered and included progression-free survival (PFS), overall survival (OS), PK, PD, and safety.
The investigators randomised 629 patients equally to 8 cycles of either GP2013-CVP (n=314) or R-CVP (n=315), followed by monotherapy maintenance for up to 2 years in responders. A total of 314 patients were given the biosimilar-, while 315 received rituximab-based treatment.
Rituximab biosimilar shows equivalent response rates
The patients had a median follow-up of 23.8 months until data cut-off on 31 December 2016. Equivalent ORR was demonstrated; the ORR was 87.1% with GP2013 compared to 87.5% with rituximab, with a difference of –0.40% (95%CI –5.94%, 5.14%).
Median PFS and OS have not been reached. However, the PFS rate was 69.9% versus 75.9%, hazard ratio [HR] 1.31 (90%CI 1.02, 1.69) and the OS rate was 92.6% versus 90.8%, HR 0.77 (90%CI 0.49, 1.22) for GP2013 versus rituximab, respectively.
According to Prof. Jurczak, the safety and immunogenicity profiles were similar between the tested agents. The PK and PD profiles were also similar and demonstrated a ratio of geometric means of 1.00 (90% CI 0.925, 1.09) for Cmax at cycle 4 day 1 and 0.939 (90% CI 0.845, 1.04) for AUEC0–21d of peripheral B-cells.
In June 2017, the European Commission approved GP2013 (Rixathon®) for use in all indications of the reference medicine.
Conclusions
The biosimilar GP2013 was compared with the originator rituximab in this study, which met its primary objective by demonstrating equivalence in ORR in patients with previously untreated, advanced follicular lymphoma, the authors concluded. Similarity between the two drugs was also demonstrated for PK, PD, safety, and immunogenicity.
GP2013 represents an important option that may help to decrease the cost of cancer care, making it sustainable for patients that benefit from rituximab.
Michele Ghielmini of the Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland who discussed the study results said that in last 20 years, thanks to rituximab, the survival of B-cell lymphomas improved by 30%. We can reasonably speculate that a biosimilar improvement in response rate will as well improve PFS and OS. However, to be sure of that we will need longer observation. At present we should trust our health authorities, and feel safe in prescribing registered rituximab biosimilars.
Disclosure
The study was funded by Hexal AG, a Sandoz company, part of the Novartis group.
Reference
994O – Jurczak W, et al. Equivalent Efficacy of a Biosimilar Rituximab and Reference Rituximab in Previously Untreated Advanced Follicular Lymphoma: Extended Results of ASSIST-FL, a Confirmatory Phase III Study.