Efficacy and safety of biosimilar ABP 980 compared with trastuzumab in HER2 positive early breast cancer

Abstract

Background: Analytical, functional, and pharmacokinetic similarity between ABP 980 and trastuzumab (TRAS) has been demonstrated. Here we report the results of primary efficacy analysis in the corresponding clinical study. Methods: The objective of this randomized, multicenter, double‐blind study was to compare ABP 980 with TRAS on pathologic complete response (pCR) in women with HER2 positive early breast cancer. After run‐in anthracycline‐based chemotherapy, patients were randomized 1:1 to intravenous ABP 980 or TRAS plus paclitaxel Q3W for 4 cycles. Patients had to complete a full cycle of run‐in therapy to be eligible for randomization. Patients continued to the adjuvant phase on IP Q3W for up to 1 year. The coprimary endpoints were risk difference (RD) and risk ratio (RR) of pCR in breast tissue and axillary lymph nodes of tumor samples. Clinical similarity was confirmed if the 2‐ sided 90% CIs for RD and RR were within the bioequivalence margin of ‐13% to 13% for RD and 0.759 to 1.318 for RR. Secondary endpoints included safety. Results: Of the 827 enrolled patients, 725 were randomized (ABP 980: n=364; TRAS: n=361); 696 (ABP 980: n=358; TRAS: n=338) were included in the pCR evaluable population. Based on local review, 48.0% and 40.5% of patients in the ABP 980 arm and TRAS arm, respectively, achieved pCR. RD and RR of pCR were 7.3% (90% CI: 1.2%, 13.4%) and 1.19 (90% CI: 1.033, 1.366), with the upper bound CI slightly exceeding the equivalence margin. Based on central independent review, 47.8% and 41.8% in the ABP 980 arm and TRAS arm achieved pCR. RD and RR of pCR were 5.8% (90% CI: ‐0.5, 12.0%) and 1.14 (90% CI: 0.993, 1.312), contained within the equivalence margin. 292 (80.2%) and 287 (79.5%) in the ABP 980 and TRAS arm, respectively, had ≥1 adverse event (AE); 54 (14.8%) patients in the ABP 980 arm and 51 (14.1%) in the TRAS arm had a Grade ≥3 AE. Most common AEs (ABP 980 vs TRAS) were arthralgia (17.3% vs 15.2%), asthenia (14.8% vs 16.3%), neutropenia (14.6% vs 12.5%), peripheral neuropathy (13.7% vs 11.9%), and anemia (11.0% vs 10.2%). Conclusions: Results of this study show clinical equivalence of ABP 980 and TRAS in the neoadjuvant setting and add to the totality of evidence demonstrating similarity between ABP 980 and TRAS.