Pertuzumab Biosimilar Shows Promise in HER2-Positive Breast Cancer Treatment

The proposed pertuzumab biosimilar QL1209 is equivalent in efficacy and safety to reference pertuzumab (Perjeta) in neoadjuvant treatment of HER2-positive, ER/PR-negative early or locally advanced breast cancer, according to a phase 3 study.¹

“QL1209 emerges as an effective biosimilar, offering a cost-effective alternative that may alleviate financial burdens and significantly contribute to the accessibility of pertuzumab for HER2-positive breast cancer patients,” wrote the authors.

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The randomized, parallel-controlled, double-blinded study, published in the British Journal of Cancer, builds on phase 1 studies, further evaluating the safety and efficacy of QL 1209 in the neoadjuvant treatment of HER2-positive, ER/PR-negative breast cancer space.

HER2 overexpression or amplification occurs in approximately 15% to 20% of breast cancer cases, contributing to poor prognoses and limited survival rates.² The introduction of dual anti-HER2 therapy, combining pertuzumab and trastuzumab with chemotherapy, has significantly improved clinical outcomes for patients with HER2-positive breast cancer by inhibiting HER2-HER3 dimerization and intracellular signaling pathways like phosphoinositide 3-kinase (PI3K)/AKT. While this therapy has become the standard of care in neoadjuvant, adjuvant, and metastatic settings, its high cost and limited accessibility have posed significant barriers to broader adoption, particularly in neoadjuvant and adjuvant settings.

The trial involved patients with HER2-positive, ER/PR-negative early, or locally advanced breast cancer from 52 centers in China. Participants were adults with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and left ventricular ejection fraction (LVEF) of at least 55%. Key exclusions included stage IV or bilateral cancer, prior antineoplastic treatments, and pregnancy/lactation.

Patients were randomized (1:1) to receive either QL1209 (biosimilar pertuzumab) or reference pertuzumab, both combined with trastuzumab and docetaxel. Treatment included four neoadjuvant cycles followed by surgery, with adjuvant therapy added per updated guidelines.

Outcomes included tumor response, adverse events, cardiac function, and pharmacokinetics. Primary and secondary end points, including pathologic complete response rates and event-free survival, were analyzed using robust statistical methods, ensuring reliability despite potential biases.

Between November 2020 and May 2022, 517 patients were randomized (n = 257 to QL1209 and 259 to reference pertuzumab) after screening, with baseline demographics and disease characteristics well balanced between the groups. The median age in both groups was 53 years, and most patients had early-stage disease (62.6% vs 63.7%). Surgical outcomes were similar, with 93.4% of patients undergoing planned surgery. Among those receiving additional adjuvant treatment, 94.9% completed chemotherapy comprised of fluorouracil, epirubicin hydrochloride, and cyclophosphamide; and 93.6% completed adjuvant QL1209 and trastuzumab treatment.

Efficacy results showed comparable pathologic complete response rates: 42.75% in the QL1209 group vs 45.17% in the reference pertuzumab group, meeting the predefined equivalence margins. Secondary end points, including overall response rates (82.49% vs 81.85%) and event-free survival (EFS), demonstrated no significant differences between the groups. Median EFS and disease-free survival were not reached, and Kaplan-Meier curves revealed no differences in outcomes across disease stages.

The safety profile was similar between QL1209 and reference pertuzumab. Treatment-emergent adverse events (TEAEs) occurred in 95.3% and 96.1% of patients, respectively, with grade 3 or higher adverse events reported in 27.2% and 28.2%. Serious adverse events and adverse events leading to treatment discontinuation were infrequent. Two deaths occurred, both unrelated to the study drugs. Pharmacokinetic analyses showed consistent profiles between the groups, and immunogenicity assessments confirmed comparable antidrug antibody positivity rates.

Despite its strengths, the trial had limitations. Protocol changes allowed for extended observations of long-term efficacy, safety, and immunogenicity, but the study concluded shortly after surgery or adjuvant treatment, limiting long-term follow-up data. While this does not undermine the primary findings, longer studies are needed to confirm QL1209's interchangeability for outcomes like event-free and disease-free survival.

References

1. Zuo W, Wang Z, Qian J. QL1209 (pertuzumab biosimilar) versus reference pertuzumab plus trastuzumab and docetaxel in neoadjuvant treatment for HER2-positive, ER/PR-negative, early or locally advanced breast cancer: a multicenter, randomized, double-blinded, parallel-controlled, phase III equivalence trial. Br J Cancer. 2024;131(4):668-675. doi:10.1038/s41416-024-02751-2

2. Loibl S, Gianni L. HER2-positive breast cancer. Lancet. 2017;389:2415-2429. doi:10.1016/s0140-6736(16)32417-5 10.1016/s0140-6736(16)32417-5