The European Union’s Committee for Medicinal Products for Human Use (CHMP) has delivered a positive opinion for Herzuma (CT-P6), a trastuzumab (Herceptin) biosimilar, for the treatment of patients with HER2-positive early breast cancer, metastatic breast cancer, or metastatic gastric cancer.
The CHMP’s opinion will now go to the European Commission (EC) for final review.
South Korea-based Celltrion, developer of the monoclonal antibody, announced the CHMP’s decision in a press release.
“By providing more treatment options, biosimilars open more opportunities for greater affordability and improve access to wider use of biotherapeutics,” said Woo Sung Kee, CEO of Celltrion, said in a statement. “Herzuma could become a cost-effective alternative to biologics for treatment of breast cancer and gastric cancer, since biologics, which cost much more than conventional anticancer drugs, place undue financial burden on patients and the general healthcare system.”
Lancet Oncology published results from a randomized, double-blind, active-controlled, phase III equivalence trial evaluating Herzuma for safety and efficacy compared with trastuzumab in June. Investigators recruited adult women with stage I–IIIa operable HER2-positive breast cancer from 112 medical facilities in 23 countries from August 2014 to May 2016.
Patients were randomly assigned patients to neoadjuvant Herzuma (n = 271) or reference trastuzumab (n = 278). Patients were treated in 3-week cycles for up to 24 weeks with 8 mg/kg Herzuma on day 1 of cycle 1 and 6 mg/kg on day 1 of cycles 2 to 8. Treatment also included 75 mg/m2 neoadjuvant docetaxel on day 1 of cycles 1 to4, along with fluorouracil, epirubicin, and cyclophosphamide (FEC) on day 1 of cycles 5 to 8.
The per protocol population included 248 patients in the Herzuma group and 256 in the trastuzumab group. Baseline characteristics were similar between the 2 groups. Randomization was stratified by clinical stage, receptor status, and country, and used permuted blocks.
Rates of pathologic complete response (pCR) were similar between the treatment arms in the intent-to-treat (ITT) population; 46.8% for Herzuma and 50.4% for trastuzumab. The estimated difference in pCR proportion between the 2 groups was –0.04 (95% CI, –0.12 to 0.05). Investigators said the 95% CI was entirely within the prespecified equivalence margin of ±0.15.
The estimated risk ratio for the pCR proportion in the per population was 0.93 (95% CI 0.78–1.11). As in the ITT population, the confidence interval entirely within the prespecified equivalence margin of 0.74 to 1.35.
Among patients who were HR-positive in the per protocol population, 40% of patients showed a pCR in the Herzuma group compared with 41% trastuzumab group. Among patients who were HR-negative, 58% of patients assigned to Herzuma showed a pCR compared with 64% in the trastuzumab group.
Investigators observed no notable differences in PK endpoints between groups at any cycle in the neoadjuvant period. In cycle 1, mean reference trastuzumab Cmax
was 186.43 μg/mL (coefficient of variation, 37.06%) in the CT-P6 group versus 178.57 μg/mL (coefficient of variation, 31.01%) in the trastuzumab group. Cmax
remained stable and similar between the two groups throughout cycles 2 to 8. Cycle 1 mean reference trastuzumab Ctrough
values were 18.92 μg/mL (coefficient of variation, 121.58%) versus 18.91 μg/mL (112.65%), remaining stable and similar between the two groups throughout cycles 2 to 8.
The percentage of patients reporting treatment-emergent adverse events (TEAEs) was 94% in the Herzuma group versus 95% with trastuzumab. The most frequent TEAEs in the Herzuma group (≥5%) were alopecia (8%), nausea (6%), neutropenia (5%), infusion-related reactions (5%), and diarrhea (5%). By comparison, the most common TEAEs in the trastuzumab group were alopecia (9%), neutropenia (9%), nausea (7%), anemia (6%), infusion-related reactions (5%), and diarrhea (4%).
Six percent of patients in the Herzuma group experienced grade ≥3 TEAEs versus 8% in the trastuzumab group.
Investigators observed TEAEs due to heart failure in 2% of patients in the Herzuma group and 1% of the trastuzumab group. Of these patients, only 1 patient in the trastuzumab group was withdrew from the study.
Stebbing J, Baranau Y, Baryas V, et al. CT-P6 compared with reference trastuzumab for HER2-positive breast cancer: a randomised, double-blind, active-controlled, phase 3 equivalence trial. Lancet Oncol. 2017; 18: 917-928. doi: 10.1016/S1470-2045(17)30434-5.