ESMO 2019 Showcases Biosimilar Equivalency Data

At the 2019 ESMO Congress, the oncology community was brought up to speed on clusters of data with biosimilars. The findings showcased that biosimilars for pegfilgrastim (Neulasta), filgrastim (Neupogen), bevacizumab (Avastin), and trastuzumab (Herceptin) demonstrated efficacy and safety equivalency with their reference counterparts in a number of malignancies.

Filgrastim Biosimilar Has Low Incidence of Chemo-Associated Febrile Neutropenia

In one study presented at the 2019 ESMO Congress, real-world results of the phase II TOPAZE trial showed that the filgrastim biosimilar (Zarxio) resulted in a low incidence of febrile neutropenia in patients who received chemotherapy with a rest period of ≤14 days.¹ A total of 1080 patients were enrolled on the study, 953 of which were included in the full data set. Patients had diffuse large B-cell lymphoma (n = 39), Hodgkin lymphoma (n = 105), breast cancer (n = 299), lung cancer (n = 144), colorectal cancer (n = 203), pancreatic cancer (n = 106), gastric cancer (n = 39), and esophageal cancer (n = 18).

Similar data were reported in patients who were receiving chemotherapy for palliative intent. Of those who received chemotherapy for curative intent, febrile neutropenia was reported in 2 patients with gastrointestinal cancer, 1 patient with lung cancer, and 7 patients with lymphoma.

Similar Efficacy, Safety Seen With Pegfilgrastim Biosimilar

Another trial presented during the conference showed that a pegfilgrastim biosimilar developed by Sandoz demonstrated similar pharmacokinetics (PK) and pharmacodynamics (PD), safety, tolerability, and immunogenicity to both US and EU reference pegfilgrastim products.²

The large, three-way, crossover phase I study comprised 577 male and female healthy volunteers. Results showed that the PK and PD were similar, and the safety profile was similar across groups. Moreover, the incidence of antidrug antibodies was similar across groups (biosimilar, 6.1%; US reference pegfilgrastim, 7.0%; EU reference pegfilgrastim, 7.8%). Additionally, the secondary PK and PD parameters were similar between both arms.

Updated Data Show Similarity With Trastuzumab Biosimilar, CT-P6 in HER2+ Early Breast Cancer

Three-year follow-up of a phase III, randomized trial continued to demonstrate equivalency between the trastuzumab (Herceptin) biosimilar CT-P6 (Herzuma; trastuzumab-pkrb) and the reference product in patients with HER2-positive early breast cancer.³ In the intent-to-treat (ITT) population, the 3-year overall survival rate was 93% and 94% with the biosimilar and trastuzumab, respectively (HR, 1.10; 95% CI, 0.57-2.13; P = .7710).

Additionally, the disease-free survival (DFS) and cardiotoxicity rates were similar between arms. The DFS rate in the ITT population at 3 years was 83% in both groups (HR, 1.23; 95% CI, 0.78-1.93; P = .3807). Due to an insufficient number of events, the median DFS and OS have not been reached.

Phase III Data Highlight Equivalency With China’s First Manufactured Trastuzumab Biosimilar

The Chinese-manufactured trastuzumab biosimilar HLX02 showed an equivalent 24-week overall response rate (ORR) compared with EU-trastuzumab in women with HER2-positive metastatic breast cancer, according to results of a phase III trial presented at the 2019 ESMO Congress.⁴

Specifically, the ORR was 71.0% (95% CI, 66.0-75.9) for HLX02 and 71.4% (95% CI, 66.5-76.3) for EU-trastuzumab. Additionally, the P value at 95% CI (P = .952) was contained within the predefined equivalence boundaries of ± 13.5%. Moreover, all secondary efficacy and safety analyses at 24 weeks also supported equivalence between the biosimilar and the reference product. No new safety signals were observed with HLX02, as well.

Bevacizumab Biosimilar Has Similar Best ORR to Reference Product in NSCLC

Also at the 2019 ESMO Congress, the proposed bevacizumab (Avastin) biosimilar SB8 showed similar efficacy in terms of best ORR risk ratio compared with the reference product in a phase III trial.⁵

In the per-protocol set, the best ORR was 50.1% with the biosimilar and 44.8% with bevacizumab. The risk difference was 5.3% (95% CI, −2.2%-12.9%], of which the lower margin was contained within and the upper margin was outside the predefined equivalence margin of (95% CI, −12.5%-12.5%). The biosimilar demonstrated equivalency with reference bevacizumab with other efficacy endpoints, safety, PK, and immunogenicity.

References

1. Phelip JM, Souquet P-J, Bordenave S, et al. Modalities of biosimilar filgrastim use in clinical practice in > 1000 patients receiving chemotherapy regimens with a rest period of ≤ 14 days: The TOPAZE study. Ann Oncol. 2019;30(suppl_5). doi: 10.1093/annonc/mdz265.057.
2. Velinova M, Bellon A, Nakov R, et al. Randomized, double-blind, cross-over phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references. Ann Oncol. 2019;30(suppl_5): doi: 10.1093/annonc/mdz265.060.
3. Stebbing J, Baranau Y, Baryash V, et al. 3-year follow-up of a phase III trial comparing the efficacy and safety of neoadjuvant and adjuvant trastuzumab and its biosimilar CT-P6 in HER2 positive early breast cancer (EBC). Ann Oncol. 2019;30(suppl_5). doi: /10.1093/annonc/mdz240.016.
4. Xu B, Zhang W, Sun T, et al. Efficacy and safety of first China-manufactured trastuzumab biosimilar HLX02 for metastatic breast cancer: a phase III trial. Ann Oncol. 2019;30(suppl_5). doi: 10.1093/annonc/mdz242.004.
5. Reck M, Luft A, Bondarenko I, et al. A phase III study comparing SB8, a proposed bevacizumab biosimilar, and reference bevacizumab in patients with metastatic or recurrent non-squamous NSCLC. Ann Oncol. 2019;30(suppl_5). doi: 10.1093/annonc/mdz260.087.