Preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer (PHranceSCa): A randomised, open-label phase II study

Abstract

The aim of the study was to assess patient preference for the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC) in patients with HER2-positive early breast cancer in PHranceSCa (NCT03674112). Materials and methods: Patients who completed neoadjuvant P þ H þ chemotherapy þ surgery were randomised 1:1 to three intravenous (IV) P þ H cycles followed by three cycles of PH FDC SC or vice versa (crossover) and then chose subcutaneous (SC) injection or IV infusion to continue up to 18 cycles (continuation). Assessments were via patient and healthcare professional (HCP) questionnaires. Results: One hundred and sixty patients were randomised (cut-off: 24 February 2020); 136 (85.0%, 95% confidence interval: 78.5e90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n Z 119) and comfort during administration (n Z 73). One hundred and forty-one patients (88.1%) were very satisfied/satisfied with SC injection versus 108 (67.5%) with IV infusion; 86.9% chose PH FDC SC continuation. HCP perceptions of median patient treatment room time ranged from 33.0e50.0 min with SC and 130.0e300.0 min with IV. Most adverse events (AEs) were grade 1/2 (no 4/5s); serious AE rates were low. AE rates before and after switching were similar (cycles 1e3 IV / cycles 4e6 SC: 77.5% / 72.5%; cycles 1e3 SC / cycles 4e6 IV: 77.5% / 63.8%). Conclusion:Most patients strongly preferred PH FDC SC over P þ H IV. PH FDC SC was generally well tolerated, with no new safety signals (even when switching), and offers a quicker alternative to IV infusion.

White Paper on the Value of Time Savings for Patients and Healthcare Providers of Breast Cancer Therapy: The Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection as an Example

“…The second clinical trial, the Phase 2 PHranceSCa study, assessed patients’ preferences, via questionnaire, for PH FDC SC or IV pertuzumab and trastuzumab after experiencing both administration methods post-surgery, following completion of neoadjuvant IV pertuzumab, trastuzumab, and chemotherapy [ 9 ]. Patients were randomized 1:1 to receive IV pertuzumab and trastuzumab for cycles 1–3, followed by PH FDC SC for cycles 4–6, or vice versa.…”

“…In the treatment room, 95.6% of HCPs agreed or strongly agreed that there was less time from start of preparation to finish of administration with PH FDC SC; 86.2%, that less resource was needed for administration; 86.8%, that PH FDC SC was more convenient for patients; and 79.2%, that PH FDC SC was better for care optimization within their treatment site [ 10 ]. These time-saving benefits were not at the cost of HCP interaction time [ 9 ].…”

A Systematic Review of Time and Resource Use Costs of Subcutaneous Versus Intravenous Administration of Oncology Biologics in a Hospital Setting

“…These results were also confirmed in the metastatic setting in the MetaspHer study (NCT01810393) [ 41 ]. The approval of a fixed-dose combination of pertuzumab and trastuzumab for SC injection (pertuzumab, trastuzumab, and hyaluronidase-zzxf (PHESGO ® , F. Hoffmann-La Roche Ltd; PH FDC SC)) [ 42 ] presents an opportunity for an option that is preferred by patients and can potentially provide time-saving benefits to patients and HCPs versus IV administration, according to patient and HCP questionnaires in the PHranceSCa study (NCT03674112) [ 43 ].…”

HLX11, a Proposed Pertuzumab Biosimilar: Pharmacokinetics, Immunogenicity, and Safety Profiles Compared to Three Reference Biologic Products (US-, EU-, and CN-Approved Pertuzumab) Administered to Healthy Male Subjects

“…Pertuzumab (Perjeta ® ) and trastuzumab are monoclonal antibodies used in the treatment of HER2-positive breast cancer [ 6 ]. Pertuzumab, a HER dimerization inhibitor, is the first humanized monoclonal antibody in a new class of drugs and is approved for use in combination with trastuzumab as therapy in HER2-positive patients [ 7 ]. Pertuzumab (Perjeta ® ) was approved for marketing in the United States (US), the European Union (EU), and China (CN) in 2012, 2015, and 2018, respectively [ 7 , 8 ].…”

“…Pertuzumab, a HER dimerization inhibitor, is the first humanized monoclonal antibody in a new class of drugs and is approved for use in combination with trastuzumab as therapy in HER2-positive patients [ 7 ]. Pertuzumab (Perjeta ® ) was approved for marketing in the United States (US), the European Union (EU), and China (CN) in 2012, 2015, and 2018, respectively [ 7 , 8 ]. Since pertuzumab binds to a different epitope than trastuzumab, combination therapy with pertuzumab and trastuzumab results in a more complete blockade of HER2 signalling than trastuzumab monotherapy.…”