The pertuzumab biosimilar TQB2440 met equivalence margins for tpCR vs reference pertuzumab in ER/PR-negative, HER2-positive early breast cancer.
TQB2440, a biosimilar referencing pertuzumab (Perjeta), demonstrated equivalent efficacy to reference pertuzumab when combined with trastuzumab and docetaxel as neoadjuvant therapy for patients with estrogen receptor (ER)/progesterone receptor (PR)–negative, HER2-positive early or locally advanced breast cancer, according to findings from a phase 3 equivalence trial (NCT05985187) published in ESMO Open.¹
The independent review committee (IRC)–assessed total pathological complete response (tpCR) rate was 58.9% with TQB2440 (n = 207) vs 58.1% with reference pertuzumab (n = 205), yielding a relative risk (RR) of 1.02 (90% CI, 0.89-1.16) that fell entirely within the prespecified equivalence margins of 0.76-1.32. A supportive analysis in the per-protocol set produced IRC-assessed tpCR rates of 62.7% and 61.9%, respectively (RR, 1.01; 90% CI, 0.89-1.15).
“Given that economic barriers impede access to pertuzumab for many patients, TQB2440, as a more cost-effective alternative, has the potential to benefit a wider patient population and reduce their treatment burden,” the study authors wrote in the paper.
Notably, reference pertuzumab is currently FDA approved for use in combination with trastuzumab and docetaxel for the treatment of adult patients with HER2-positive metastatic breast cancer who have not previously received HER2-directed therapy or chemotherapy for metastatic disease.2 The agent is also indicated for use in combination with trastuzumab and chemotherapy for the neoadjuvant treatment of adult patients with HER2-positive locally advanced, inflammatory, or early stage breast cancer; as well as for the adjuvant treatment of adult patients with HER2-positive early breast cancer that is at high risk of recurrence.
The multicenter, randomized, double-blind, parallel-controlled trial enrolled patients from 56 centers in China between October 21, 2020, and August 14, 2022.1 Eligible patients were 18 to 75 years with histologically confirmed, previously untreated primary breast cancer (tumor diameter > 2 cm or positive lymph nodes), centrally or locally confirmed HER2 positivity, clinical stage II to IIIC disease, an ECOG performance status of 0 or 1, and ER/PR-negative status.
TQB2440 vs Reference Pertuzumab in Neoadjuvant HER2+ Breast Cancer: Trial Highlights
A total of 412 patients were randomly assigned 1:1, stratified by lymph node status, to receive TQB2440 or reference pertuzumab, each at 840 mg on day 1 of cycle 1 followed by 420 mg in cycles 2 to 4; plus trastuzumab at 8 mg/kg on day 1 of cycle 1 followed by 6 mg/kg on cycles 2 to 4; and docetaxel at 75 mg/m². Treatment was administered for 4 cycles every 3 weeks before surgery. Adjuvant treatment consisted of fluorouracil/epirubicin/cyclophosphamide chemotherapy for cycles 5 to 7 followed by TQB2440 plus trastuzumab through cycle 20. The primary end point was IRC-assessed tpCR (ypT0/is, ypN0). Baseline characteristics were balanced, with a median age of 53 years and clinically involved lymph nodes in 71.0% and 69.3% of patients in the 2 groups, respectively.
The secondary end points reinforced the equivalence findings. The investigator-assessed tpCR was 60.4% with TQB2440 vs 58.1% with reference pertuzumab (RR, 1.04; 90% CI, 0.91-1.19). Breast pathological complete response rates were comparable between these respective arms whether assessed by IRC (67.6%; 95% CI, 60.8%-74.0% vs 63.9%; 95% CI, 56.9%-70.5%) or the investigators (65.7%; 95% CI, 58.8%-72.1% vs 62.0%; 95% CI, 54.9%-68.6%). The objective response rate was 73.9% (95% CI, 67.4%-79.8%) with TQB2440 vs 67.3% (95% CI, 60.4%-73.7%) with reference pertuzumab, and the breast-conserving surgery rates were 13.0% (95% CI, 8.8%-18.4%) vs 13.2% (95% CI, 8.9%-18.6%), respectively. At median follow-ups of 18.4 months and 17.9 months, respectively, the median event-free survival and disease-free survival were not reached in either arm because of insufficient events.
Treatment-emergent adverse events (TEAEs) during neoadjuvant therapy occurred in 99.5% of patients receiving TQB2440 and 100.0% of those receiving reference pertuzumab, with grade 3 or higher TEAEs reported in 79.7% and 81.4% of patients, respectively. The most frequent grade 3 or higher TEAEs in these respective arms were decreased neutrophil count (72.5% vs 70.1%) and decreased white blood cell count (64.3% vs 59.8%). Treatment-related AEs of any grade were reported in 79.7% vs 76.0% of patients, respectively, and serious AEs occurred in 22.7% vs 25.0% of patients, respectively. One death from sepsis, considered possibly unrelated to study treatment, occurred in the TQB2440 group.
Cardiotoxicity rates, a focus given the association between the regimen and heart failure risk, were comparable between the respective arms (1.9% vs 1.5%); a single grade 3 or higher cardiotoxicity event—palpitations—was reported in 1 patient in the reference pertuzumab group.
The pharmacokinetic profiles were similar between the arms across 400 patients analyzed. Anti-drug antibodies were detected in 4 patients (2.0%) who received TQB2440 and 3 patients (1.5%) who received reference pertuzumab.
The study authors noted that longer follow-up is needed to characterize long-term efficacy and cardiac safety of TQB2440, and that trial enrollment restricted to ER/PR-negative disease may limit the generalizability of these findings to ER-positive, HER2-positive disease.
