Occurring in up to 20 percent of breast cancers, HER2 overexpression is linked to high disease recurrence and poor survival outcomes. At the Hong Kong Breast Cancer Foundation (HKBCF) Annual Breast Cancer Updates 2024 meeting, Professor Matteo Lambertini from University of Genova, Italy, discussed the benefits of adding pertuzumab to trastuzumab and chemotherapy in managing HER2-positive (HER2+) early breast cancer (EBC), while a real-world case was shared by Dr Josephine Tsang from Queen Mary Hospital, Hong Kong.
pCR as a prognostic factor
“The latest European Society for Medical Oncology guidelines on HER2+ EBC recommended that only patients with cT1N0 disease should initially undergo primary surgery ± radiotherapy,” stated Lambertini. “For the majority of patients, neoadjuvant treatment should be used.” [Ann Oncol 2024;35:159-182]
Pathological complete response (pCR) rate is a key factor in selecting an appropriate neoadjuvant treatment regimen, as achieving pCR is known to be associated with reduced risk of disease recurrence and improved survival outcomes. Combining chemotherapy with dual HER2 blockade (ie, pertuzumab plus trastuzumab [P + H]) yields higher pCR rates than trastuzumab alone, potentially leading to better long-term outcomes, especially in patients with lymph node (LN)–positive disease. [Ann Oncol 2024;35:159-82; JAMA Oncol 2020;6:e193692]
“Importantly, even if patients achieve pCR after treatment, tumour size and nodal status remain crucial prognostic factors,” added Lambertini.
P + H in neoadjuvant–adjuvant treatment
Focusing on the Asian population, the PEONY trial (n=329) evaluated the efficacy of adding pertuzumab to neoadjuvant trastuzumab and chemotherapy in patients with early or locally advanced breast cancer. A total pCR rate of 39.3 percent was achieved with pertuzumab vs 21.8 percent with placebo (p=0.001). [JAMA Oncol 2020;6:e193692]
The trial’s long-term efficacy analysis demonstrated higher 5-year event-free survival (EFS) and disease-free survival (DFS) rates with pertuzumab vs placebo (EFS: 84.8 vs 73.7 percent; hazard ratio [HR], 0.53; 95 percent confidence interval [CI], 0.32–0.89; DFS: 86.0 vs 75.0 percent; HR, 0.52; 95 percent CI, 0.30–0.88). (Figure) [Nat Commun 2024;15:2153]
P + H in adjuvant treatment
P + H also improves outcomes in the adjuvant setting. In the APHINITY trial, patients with LN-positive EBC achieved a significantly higher 3-year invasive disease–free survival (iDFS) rate with pertuzumab vs placebo (92.0 vs 90.2 percent; HR, 0.77; 95 percent CI, 0.62–0.96; p=0.02). The iDFS benefit in the LN-positive cohort was sustained in the long term, with 8-year iDFS rates of 86.1 vs 81.2 percent in the pertuzumab vs placebo group (HR, 0.72; 95 percent CI, 0.60–0.87). [N Eng J Med 2017;377:122-131; J Clin Oncol 2024;42:3643-3651]
Real-world evidence supporting the efficacy of P + H is further illustrated in the below case study of a Hong Kong Chinese patient.
Benefits of SC administration
Traditional intravenous (IV) administration of P + H often requires prolonged infusion times of up to 90 minutes per treatment cycle. This invasive, time-consuming approach is painful for patients and also creates a burden on the healthcare system. [Lancet Oncol 2021;22:85-97]
Subcutaneous (SC) P + H is considered a convenient alternative. It contains antibodies that are identical to IV formulation and is formulated with recombinant human hyaluronidase to allow SC administration of higher drug volumes (600/600 mg, 10 mL; 1,200/600 mg, 15 mL). Prepared in a ready-to-use fixed-dose formulation, SC injection takes only 8 minutes for loading and 5 minutes for maintenance. [Phesgo Hong Kong Prescribing Information, 2022]
The FeDeriCa trial showed that the fixed-dose combination of P + H for SC injection with chemotherapy was noninferior to the IV formulation in the neoadjuvant setting (90 percent CI, 1.14–1.31) based on cycle 7 pertuzumab serum Ctrough concentrations. Total pCR rates were also comparable (59.5 vs 59.7 percent), with a similar safety profile. [Lancet Oncol 2021;22:85-97]
Patients’ preference for the SC formulation was established in the PHranceSCa study, where 85 percent of patients preferred SC P + H over the IV formulation, mainly due to reduced clinic time (42 percent) and comfort during administration (26 percent). [Eur J Cancer 2021;152:223-232]
Compared with IV administration, SC P + H reduces the time required for patients to spend in hospital, thereby saving healthcare professionals’ time and optimizing the use of medical resources. [Lancet Oncol 2021;22:85-97]
The above content is supported by the industry.
