Biosimilar Rituximab Suggests Equivalent Efficacy For Advanced Follicular Lymphoma

Two phase III trials of advanced follicular lymphoma indicate comparable efficacy and tolerability between biosimilar formulations and originator rituximab

medwireNews: Phase III results for two biosimilar formulations of rituximab suggest that they induce an equivalent response to the branded CD20 inhibitor in patients with advanced follicular lymphoma.

“Rituximab biosimilars have potential cost-saving benefits for health care, and can also improve the accessibility of rituximab-containing treatment worldwide”, say Shinichi Makita and Kensei Tobinai, both from the National Cancer Center Hospital in Tokyo, Japan, in a comment accompanying the articles in The Lancet Oncology.

“The results of these two trials will certainly promote the introduction of rituximab biosimilar into daily, clinical practice in the immediate future.”

The first of the studies, by Bertrand Coiffier, from Hospices Civils de Lyon in France, and co-authors, compared the biosimilar CT-P10 and originator rituximab in patients with treatment-naive, Ann Arbor stage III–IV follicular lymphoma. The patients were randomly assigned to receive a 375 mg/m2 dose of CT-P10 or rituximab on day 1 of a 21-day cycle, alongside cyclophosphamide, vincristine and prednisone (CVP) chemotherapy. The primary endpoint of overall response at the end of eight cycles of treatment was achieved by 97.0% of the 66 patients given the biosimilar regimen and 92.6% of the 68 patients given the originator rituximab. The 4.3% difference in favour of the CT-P10 regimen "lay on the positive side of the predefined non-inferiority margin", the researchers say. Pharmacokinetic analysis indicated that the serum concentration–time curve at steady state and the maximum serum concentration at steady state were also comparable between the treatment groups, with all confidence intervals within the bioequivalence margin, add Bertrand Coiffier et al. Neutropenia was the most common grade 3 or 4 treatment-emergent adverse event (AE) in both the CT-P10 and rituximab groups, at 21% and 10%, respectively. One or more serious AEs were reported in 23% and 13% of patients, respectively. Noting that CT-P10 is the first rituximab biosimilar to be approved by the European Medicines Agency (EMA), the authors conclude: "This phase 3 trial is ongoing, and longer-term data for patients with advanced-stage follicular lymphoma on maintenance therapy will be assessed when available."

Results from the second trial – ASSIST-FL – of the biosimilar GP2013 versus rituximab, both given alongside CVP, also showed an equivalent overall response in the two arms, at 87% of 311 patients versus 88% of 313 patients.

The patients were randomly assigned to receive eight cycles of biosimilar or originator rituximab plus CVP, followed by 2 years of monotherapy maintenance in participants who achieved a response, explain Wojciech Jurczak, from Jagiellonian University Medical College in Krakow, Poland, and co-investigators.

Patients in the biosimilar and rituximab arms also had similar rates of AEs (93 vs 91%) and serious AEs (23 vs 20%), with neutropenia the most common event in both the combination (26 vs 30%) and maintenance phase (10 vs 6%).

Antibodies against the anti-CD20 agent developed in 2% of the biosimilar group and 1% of the rituximab group, prompting the authors to comment on their EMA-approved product: “Our results show that GP2013 represents a viable rituximab biosimilar candidate for patients with previously untreated advanced follicular lymphoma.”

Commentators Shinichi Makita and Kensei Tobinai caution that overall response is “not a robust endpoint to evaluate the efficacy of therapeutic modalities for previously untreated follicular lymphoma”, although they admit that both the EMA and US Food and Drug Administration allow this endpoint for evaluation of biosimilar and originator products.

They also note that CHOP chemotherapy plus bendamustine is more commonly used than CVP for patients with follicular lymphoma, and that both subcutaneous rituximab and the anti-CD20 agent obinutuzumab remain competitors of originator rituximab in this setting.

References

Kim WS, Buske C, Ogura M, et al. Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial. Lancet Haematol; Advance online publication 13 July 2017. DOI: http://dx.doi.org/10.1016/S2352-3026(17)30120-5

Jurczak W, Moreira I, Kanakasetty GB, et al. Rituximab biosimilar and reference rituximab in patients with previously untreated advanced follicular lymphoma (ASSIST-FL): primary results from a confirmatory phase 3, double-blind, randomised, controlled study. Lancet Haematol; Advance online publication 13 July 2017. DOI: http://dx.doi.org/10.1016/S2352-3026(17)30106-0

Makita S, Tobinai K. Rituximab biosimilars: introduction into clinical practice. Lancet Haematol; Advance online publication 13 July 2017. DOI: http://dx.doi.org/10.1016/S2352-3026(17)30124-2

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