Neoadjuvant therapy with HD201 is as effective as trastuzumab in patients with ERBB2-positive breast cancer, according to phase 3 results published in JAMA Oncology

In the double-blind, phase 3 TROIKA trial ( Identifier: NCT03013504), researchers compared the biosimilar HD201 with referent trastuzumab in patients with ERBB2-positive early breast cancer.

The study enrolled 502 patients across 70 sites in 12 countries. The patients were randomly assigned to receive HD201 (250 patients) or referent trastuzumab (252 patients) as neoadjuvant therapy for 8 cycles, in combination with 4 cycles of docetaxel, which was followed by 4 cycles of epirubicin and cyclophosphamide. After surgery, patients received 10 cycles of either HD201 or trastuzumab.

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Baseline characteristics were well balanced between the treatment arms. Overall, the median age was 53 years (range, 26 to 82 years), 38.8% of patients were hormone receptor-negative, and 42.4% had stage III disease.

After the completion of the adjuvant phase, with a median follow-up of 31 months, the total pathological complete response (tpCR) rate was 45.0% in the HD201 arm and 48.7% in the trastuzumab arm.

The difference in tpCR between the treatment arms was -3.8% (95% CI, -12.8 to 5.4), which was insignificant and fell within the predefined equivalence margins. The ratio of the tpCR rates between the arms was 0.92 (95% CI, 0.76-1.12).

Pharmacokinetic analysis showed mean trough concentration (Ctrough) levels of 42.7 μg/mL with HD201 and 43.6 μg/mL with trastuzumab at the onset of cycle 5, and 53.8 μg/mL with HD201 and 53.7 μg/mL with trastuzumab at the onset of cycle 8.

The mean difference in the Ctrough levels between the treatment arms was -2.0% (95% CI, −10.5 to 6.5) for cycle 5 and 0.3% (95% CI, −6.2 to 6.8) for cycle 8, implying the bioequivalence of HD201 to referent trastuzumab for Ctrough.

Treatment-emergent adverse events (TEAEs) were observed in nearly all patients in both arms. Serious TEAEs occurred in 9.6% of patients in the HD201 arm and 6.7% in the trastuzumab arm. Treatment discontinuation due to TEAEs was reported in 6.4% of patients in the HD201 arm and 4.8% in the trastuzumab arm.

There were a total of 2232 TEAEs of special interest, occurring in 88.0% of patients in the HD201 arm and 84.5% in the trastuzumab arm. These TEAEs included cardiotoxic effects, infusion site reactions, hypersensitivity, hematotoxicity, pulmonary disorders, and infections.

There were 4 cardiovascular-related deaths in the HD201 arm, all of which were considered unrelated or unlikely to be related to the study treatment. There were 2 deaths due to disease progression.

“This phase 3 study demonstrated the equivalence between HD201 and referent trastuzumab in terms of efficacy for the tpCR endpoint and safety,” the researchers wrote. “These results support the application submitted for registration of HD201 as a biosimilar of trastuzumab.”

Disclosures: This research was supported by Prestige BioPharma Ltd. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Pivot X, Georgievich MA, Shamrai V, et al. Efficacy of HD201 vs referent trastuzumab in patients with ERBB2-positive breast cancer treated in the neoadjuvant setting: A multicenter phase 3 randomized clinical trial. JAMA Oncol. Published online March 03, 2021. doi:10.1001/jamaoncol.2021.8171