Neoadjuvant Pertuzumab Biosimilar Plus Trastuzumab/Docetaxel Meets pCR End Point in HER2+ Breast Cancer

Neoadjuvant treatment with HLX11—a biosimilar referencing pertuzumab (Perjeta)—in combination with trastuzumab (Herceptin) and docetaxel met the total pathological complete response (pCR) rate primary end point in patients with HER2-positive, hormone receptor (HR)–negative, early-stage or locally advanced breast cancer, according to data from a phase 3 study (NCT05346224).¹

The study evaluated the combination of HLX11, trastuzumab, and docetaxel vs pertuzumab plus trastuzumab and docetaxel, and the total pCR primary end point was assessed by an independent review committee. Analysis is ongoing for the trial’s secondary end points, which include investigator-assessed total pCR rate, breast pCR rate, objective response rate, event-free survival, disease-free survival, safety, pharmacokinetics, and immunogenicity.

In the United States, pertuzumab is currently approved in combination with trastuzumab and docetaxel for treatment of patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease; in combination with trastuzumab and chemotherapy as neoadjuvant treatment for patients with HER2-positive, locally advanced, inflammatory, or early-stage breast cancer as part of a complete treatment regimen for early breast cancer; and in combination with trastuzumab and chemotherapy for the adjuvant treatment of patients with HER2-positive early-stage breast cancer at high risk of recurrence.²

The phase 3, multicenter, double-blind, randomized, parallel-controlled, equivalence study enrolled patients at least 18 years of age with histologically confirmed invasive breast carcinoma with a primary tumor size of more than 2 cm per local assessment.³ Those with early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0) disease were allowed to enroll. Patients were required to have centrally confirmed HER2-positive disease (immunohistochemistry 3+ or 2+/in situ hybridization positive) and HR-negative disease (less than 1% nuclear staining for the estrogen receptor and progesterone receptor).

Other key inclusion criteria consisted of a baseline left ventricular ejection fraction of at least 55%, and adequate hematologic, liver, and renal function. Patients were excluded if they had inflammatory breast cancer; had stage IV disease, bilateral breast cancer, or multicentric breast cancer; had a history of another malignancy within 5 years of screening, other than carcinoma in situ of the cervix, basal cell carcinoma, or squamous cell carcinoma of the skin that underwent radical treatment; or had serious heart disease.

Patients were randomly assigned 1:1 to receive HLX11 or pertuzumab in combination with trastuzumab and docetaxel.¹ In the neoadjuvant setting, HXL11 and pertuzumab were both administered with a loading dose of 840 mg, followed by subsequent doses of 420 mg once every 3 weeks for up to 4 cycles. In the adjuvant setting, the agents were given at a loading dose of 840 mg, followed by subsequent doses at 420 mg once every 3 weeks for up to 13 cycles.³

In both arms, other neoadjuvant treatment included trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg once every 3 weeks for up to 4 cycles, plus docetaxel at 75 mg/m² once every 3 weeks for up to 4 cycles. Other adjuvant treatment consisted of doxorubicin at 60 mg/m² once every 3 weeks for up to 4 cycles, cyclophosphamide at 600 mg/m² once every 3 weeks for up to 4 cycles, and trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg, once every 3 weeks for up to 13 cycles.

Study drugs were administered on the same day every 3 weeks. In the neoadjuvant setting, trastuzumab was given first, followed by HLX11/pertuzumab and docetaxel. In the adjuvant setting, doxorubicin plus cyclophosphamide was administered first, followed by trastuzumab and HLX11/pertuzumab.

Key stratification factors included disease stage (early-stage vs locally advanced) and geographic region (Asia vs non-Asia).

References

1. Phase 3 comparative clinical study of Perjeta (pertuzumab) biosimilar candidate HLX11. News release. Shanghai Henlius Biotech. September 30, 2024. Accessed October 4, 2024. https://www.henlius.com/en/NewsDetails-4726-26.html
2. Perjeta. Prescribing information. Genentech; 2021. Accessed October 4, 2024. https://www.gene.com/download/pdf/perjeta_prescribing.pdf
3. A study to evaluate the efficacy and safety of HLX11 vs. EU-Perjeta in the neoadjuvant therapy of HER2-positive and HR-negative early-stage or locally advanced breast cancer. ClinicalTrials.gov. Updated April 16, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT05346224