Trastuzumab Biosimilar Efficacy Sustained With Updated Data

Adjuvant treatment with the trastuzumab (Herceptin) biosimilar CT-P6 (Herzuma; trastuzumab-pkrb) demonstrated comparable efficacy and safety to the reference product in patients with HER2-positive early breast cancer, according to results of posthoc analyses of a phase III trial (NCT02162667).¹

The FDA approved the biosimilar in December 2018 for the treatment of patients with HER2-overexpressing breast cancer. The decision was based on an extensive review of a comprehensive data package, which included foundational analytical similarity data, nonclinical data, clinical pharmacology, immunogenicity, clinical efficacy, and safety data.²

Prior data from the double-blind, parallel group, active-controlled phase III trial showed that the biosimilar demonstrated equivalent efficacy to reference trastuzumab in the neoadjuvant setting.³ In the updated findings, researchers reported on pathological complete response (pCR), breast pCR, and efficacy and safety measures of a subgroup analysis in the adjuvant setting.

In the study, patients were female and aged ≥18 years with pathologically confirmed, newly diagnosed, operable, HER2-positive early breast cancer that was clinical stage I, II, or IIIA, which was classified according to the American Joint Committee on Cancer Breast Cancer Staging 7th edition. Patients were recruited from 112 centers in 23 countries and patient characteristics were similar between arms.

Neoadjuvant therapy comprised eight 3-week cycles of CT-P6 (n = 258) or trastuzumab (n = 261) at a loading dose of 8 mg/kg followed by 6 mg/kg for cycles 2 through 8, along with a chemotherapy regimen of docetaxel and fluorouracil, epirubicin, and cyclophosphamide.

Then, patients received adjuvant treatment with CT-P6 (n = 271) or reference trastuzumab (n = 278) at 6 mg/kg at 90-minute intravenous infusions every 3 weeks until ≤1 year from the initial neoadjuvant dose or ≤10 cycles after surgery. Additionally, patients received radiation therapy or hormonal therapy in the adjuvant setting at the investigator’s discretion. Follow-up will continue post-treatment for ≤3 years from the enrollment date of the last patient.

Endpoints assessed during the adjuvant setting included progressive disease, and the proportion of patients receiving post-surgery radiation or hormonal therapy. Future analyses will explore disease-free survival and progression-free survival.

Results showed that the pCR rates and breast pCR rates continued to be comparable between treatment arms, regardless of patient characteristics that included age, region, or clinical stage and were similar to the neoadjuvant data.

Those data showed that the proportion of patients who achieved pCR were similar with CT-P6 and trastuzumab, at 46.8% (95% CI, 40.4-53.2) and 50.4% (95% CI, 44.1-56.7), respectively. The 95% CI of the estimated treatment outcome difference (−0.04; 95% CI, −0.12-0.05) was within the equivalence margin.

In the adjuvant data, in patients ≥65 years, the pCR rates with CT-P6 versus trastuzumab were 45.2% (95% CI, 27.3-64.0) and 50.0% (95% CI, 33.8-66.2), respectively, leading to a difference of —0.05 (95% CI, –0.28-0.19). For those <65 years, the pCR rates were 43.3% (95% CI, 37.0-49.9) and 46.6% (95% CI, 40.2-77.3) with CT-P6 and reference trastuzumab, respectively, which led to an estimated difference of –0.03 (95% CI, –0.28-0.19).

Additionally, the breast pCR rates in patients ≥65 years were 54.8% (95% CI, 36.0-72.7) with CT-P6 and 62.5% (95% CI, 45.8-77.3) with trastuzumab, demonstrating an estimated treatment difference of —0.08 (95% CI, –0.31-0.16). In patients <65 years, the breast pCR rate was 48.3% (95% CI, 41.9-54.9) and 50.4% (95% CI, 43.9-56.9) with CT-P6 and trastuzumab, respectively, which showed a treatment difference of –0.02 (–0.11-0.07).

In the intent-to-treat population, 15 patients experienced recurrent or progressive disease (PD) at 1 year, 9 in the biosimilar arm and 6 in the trastuzumab arm. Results were similar in the per-protocol set, as 6 patients on CT-P6 and 5 patients on reference trastuzumab had PD.

Overall, 47.6% and 52.2% of patients on CT-P6 and trastuzumab, respectively, experienced treatment-emergent adverse events (TEAEs). This included 17 patients with heart failure (CT-P6, 10; trastuzumab, 7). There were 2 TEAE-related discontinuations in the biosimilar arm and 3 discontinued in the reference trastuzumab arm.

References

1. Esteva FJ, Baranau YV, Baryash V, et al. Efficacy and safety of CT-P6 versus reference trastuzumab in HER2-positive early breast cancer: updated results of a randomised phase 3 trial [published online ahead of print August 19, 2019]. Cancer Chemo and Pharma. doi: 10.1007/s00280-019-03920-4.
2. Celltrion and Teva announce FDA approval of Herzuma (trastuzumab-pkrb), a biosimilar to Herceptin, for the treatment of HER2-overexpressing breast cancer for certain indications [news release]. Incheon, South Korea, and Jerusalem, Israel: Celltrion. Published December 14, 2018. https://bit.ly/2KY6s8i. Accessed December 17, 2018.
3. Esteva FJ, Lee S, Yu S, et al. 24 months results from a double-blind, randomized phase III trial comparing the efficacy and safety of neoadjuvant then adjuvant trastuzumab and its biosimilar candidate CT-P6 in HER2 positive early breast cancer (EBC). Lancet Oncol. 2017;18(7):917-928. doi: 10.1016/S1470-2045(17)30434-5.