Researchers Report Findings on Three Biosimilar Trastuzumab Products

During the 2018 American Society of Clinical Oncology's (ASCO) Annual Meeting, researchers presented findings on 3 biosimilar trastuzumab products: Samsung Bioepis’ SB3, Agmen’s ABP 980, and Biocad’s Herticad.

One-year safety and survival data for SB3 support biosimilarity

SB3, which is approved in the European Union as Ontruzant and is under review by the FDA, was the subject of a report on safety and survival data from patients with HER2-positive early or locally advanced breast cancer. In a clinical trial,¹ patients received either SB3 or the reference trastuzumab and had follow-up of at least 12 treatment-free months after 12 cycles of neoadjuvant-adjuvant therapy.

In total, 367 patients were randomized to receive 8 cycles of either SB3 (n = 186) or the reference trastuzumab (n = 181) in the neoadjuvant setting together with chemotherapy. Patients then underwent surgery and another 10 cycles of SB3 or the reference trastuzumab.

Patients were followed up every 6 months to observe the incidence of symptomatic congestive heart failure, asymptomatic significant left ventricular ejection fraction (LVEF) decrease, cardiac events, event-free survival (EFS), and overall survival (OS). The median follow-up from initiation of the study was 30.1 months for the SB3 arm and 30.2 months for the reference arm.

During the 1-year follow-up, the incidence of asymptomatic significant LVEF decrease was similar in the SB3 group (n = 1) and reference group (n = 2), and no significant cardiac conditions or cardiac-related death were reported.

In total, 8 patients in the SB3 group and 14 in the reference group experienced disease recurrence, progression, or death. In the SB3 arm, there was 1 patient death, and in the reference arm, there were 3 patient deaths. At 24 months, EFS rates (SB3, 96.7%; reference, 94.3%) and OS rates were comparable between groups (SB3, 100.0%; reference, 99.4%).

These results, say the authors, further support the biosimilarity of SB3 with its reference.

Central evaluations from LILAC further support clinical equivalence of ABP 980 and reference trastuzumab

One day after Amgen revealed that the FDA had issued a Complete Response Letter for its ABP 980 (which was authorized for marketing in Europe under the name Kanjinti in May 2018), researchers reported results of a pathologic complete response (pCR) analysis based on central laboratory evaluation of tumor samples collected in the phase 3, randomized, multicenter, double-blind, active-controlled LILAC study that compared ABP 980 to reference trastuzumab in patients with HER2-positvive early breast cancer.² Results from a local laboratory evaluation were previously reported.

In the LILAC study, 725 patients were randomized to receive either the biosimilar (n = 696) or the reference trastuzumab (n = 338) plus paclitaxel after run-in chemotherapy. The coprimary endpoints were risk difference (RD) and risk ratio (RR) of pCR adjusted for baseline covariates in breast tissue and axillary lymph nodes, and clinical similarity of the trastuzumab products was supported if the 2-sided 90% confidence intervals (CIs) were within the equivalence margin for RD (—13%-13%) and RR (0.759-1.318). Each sample was evaluated by 2 independent central pathologists.

The researchers report that, based on central review, pCR was achieved in 47.8% of patients receiving ABP 980 and 41.8% of those receiving the reference product. The RD was 5.8% (90% CI, —0.5-12.0%), and the RR was 1.14 (90% CI, 0.993-1.312); both the RD and RR fell within the prespecified equivalence margins.

The researchers say that the results of the central evaluations further support the clinical equivalence of the biosimilar and its reference, and also support the feasibility of including central laboratory review of pCR rates in a large, multicenter, multinational studies.

Biocad’s Herticad reduced the cost of trastuzumab therapy by 75%

Biocad’s Herticad, which is approved for use in Russia, has been available since 2016, and new research reports on the effectiveness, safety, and economics of using the biosimilar in clinical practice.³

Researchers conducted a study that included 55 women with stage 2 or stage 3 HER2-positve breast cancer who were treated at Russia’s National Research Cancer Center from March 2016 to December 2017. All patients received neoadjuvant chemotherapy together with the biosimilar trastuzumab, after which all patients had surgery with an assessment of pCR.

The rate of pCR was 55.6% in the breast and 45.8% in the breast and lymph nodes, and was similar in patients with primary-operable and locally-advanced disease. There were no reports of treatment-associated cardiac dysfunction in any of the patients, nor were there any infusion-related reactions.

The cost to provide neoadjuvant therapy with trastuzumab decreased 75% during the study period by using the biosimilar, and the researchers report that the biosimilar provides an economically reasonable option that is both safe and effective.

References

1. Pivot X, Bondarenko I, Nowecki Z, et al. Additional one-year follow-up study to evaluate safety and survival in patients who have completed neoadjuvant-adjuvant treatment with SB3 (trastuzumab biosimilar) or reference trastuzumab in HER2-positive early or locally advanced breast cancer. J Clin Oncol. 2018;36 (suppl; Abstract e12631).

2. Kolberg HC, Tomasevic Z, Demetriou G, et al. Efficacy analyses of central laboratory pCR results from the LILAC study comparing the biosimilar ABP 980 and trastuzumab. J Clin Oncol. 2018;36 (suppl; Abstract 583).

3. Kolyadina IV, Ganshina I, Zhukova L, et al. The effectiveness, safety and economic rationality of the neoadjuvant chemotherapy with biosimilar of trastuzumab in HER2+ breast cancer in Russian clinical practice. J Clin Oncol. 2018;36 (suppl; Abstract e12656).