RESUMO
AIM: 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 + H + chemotherapy + surgery were randomised 1:1 to three intravenous (IV) P + 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: 78.5-90.2%) preferred SC; 22 (13.8%) preferred IV; 2 (1.3%) had no preference. The main reasons for SC preference were reduced clinic time (n = 119) and comfort during administration (n = 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 33.0-50.0 min with SC and 130.0-300.0 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 1-3 IV â cycles 4-6 SC: 77.5% â 72.5%; cycles 1-3 SC â cycles 4-6 IV: 77.5% â 63.8%). CONCLUSION: Most patients strongly preferred PH FDC SC over P + 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.
Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/terapia , Terapia Neoadjuvante/métodos , Preferência do Paciente/estatística & dados numéricos , Trastuzumab/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/psicologia , Quimioterapia Adjuvante/estatística & dados numéricos , Estudos Cross-Over , Combinação de Medicamentos , Feminino , Humanos , Infusões Intravenosas/efeitos adversos , Infusões Intravenosas/psicologia , Injeções Subcutâneas/efeitos adversos , Injeções Subcutâneas/psicologia , Pessoa de Meia-Idade , Terapia Neoadjuvante/psicologia , Terapia Neoadjuvante/estatística & dados numéricos , Estadiamento de Neoplasias , Satisfação do Paciente , Receptor ErbB-2/análise , Receptor ErbB-2/metabolismo , Adulto JovemRESUMO
Treatment of HER2-positive early breast cancer (EBC) continues to evolve with neoadjuvant (pre-operative) and adjuvant (post-operative) HER2-targeted therapies as standard of care. There are two important decision points. The first involves deciding between neoadjuvant therapy or proceeding directly to surgery. Neoadjuvant chemotherapy (NACT) plus pertuzumab-trastuzumab is appropriate for patients with high-risk HER2-positive EBC (tumour diameter ≥2 cm, and/or node-positive disease). Patients with node-negative disease and tumour diameter <2 cm are candidates for upfront surgery followed by paclitaxel for 12 weeks plus 18 cycles of trastuzumab, with the option to add pertuzumab (if pN+). The second decision point involves the pathohistological result at surgery after neoadjuvant therapy. Total pathological complete response (tpCR: ypT0/is, ypN0) is associated with improved survival endpoints. Patients with tumours ≥2 cm and/or node-positive disease at diagnosis who have a tpCR after dual blockade should continue pertuzumab-trastuzumab in the adjuvant setting to complete 1 year (18cycles) of treatment. For patients with invasive residual disease, 14cycles of post-neoadjuvant trastuzumab emtansine (T-DM1) therapy significantly increases invasive-DFS compared with trastuzumab. Extended adjuvant therapy with neratinib is an option in selected patients (HER2-positive and oestrogen receptor [ER]-positive) who have completed adjuvant trastuzumab-based therapy. Less aggressive chemotherapy regimens are recommended in populations with a lower risk of recurrence (patients with small tumours without axillary involvement; patients unlikely to tolerate anthracycline-taxane or taxane-carboplatin regimens). Ultimately, treatment recommendations should be consistent with local and international guidelines. Further studies will guide optimisation of treatment for patients with HER2-positive EBC according to the risk of disease recurrence.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Tomada de Decisões , Receptor ErbB-2/antagonistas & inibidores , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ensaios Clínicos Fase I como Assunto , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Metástase Linfática , Oncologia/normas , Terapia Neoadjuvante , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Fatores de RiscoRESUMO
PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2-positive breast cancer. Pertuzumab is currently approved with an initial loading dose of 840 mg, followed by a 420-mg maintenance dose intravenously every 3 weeks. A reloading dose is required if there is a ≥6-week delay in treatment. In response to the potential treatment disruption due to COVID-19, the impact of dose delays and alternative dosing regimens on intravenous pertuzumab for human epidermal growth factor receptor 2-positive breast cancer treatment is presented. Simulations were conducted by using the validated population pharmacokinetic model for pertuzumab, and included (1) 4-, 6-, and 9-week dose delays of the 840 mg/420 mg every 3 weeks dosing regimen and (2) 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens. Simulations were compared with the currently approved pertuzumab dosing regimen. The simulations in 1000 virtual patients showed that a dose reload (840 mg) is required following a dose delay of ≥6 weeks to maintain comparable Ctrough (lowest concentration before the next dose is given) levels to clinical trials. The 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens decrease median steady-state Ctrough by ≈40% compared with the approved regimen, and <90% of patients will be above the target Ctrough . Thus, the alternative 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks pertuzumab dosing regimens are not recommended. Flexibility for intravenous PERJETA-based regimens is available with an alternative route of pertuzumab administration (subcutaneous vs intravenous).
Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias da Mama/tratamento farmacológico , Relação Dose-Resposta a Droga , Quimioterapia de Manutenção/métodos , Receptor ErbB-2/antagonistas & inibidores , Tempo para o Tratamento , Trastuzumab , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Simulação por Computador , Quimioterapia de Consolidação/métodos , Vias de Administração de Medicamentos , Esquema de Medicação , Feminino , Humanos , Controle de Infecções/métodos , SARS-CoV-2 , Trastuzumab/administração & dosagem , Trastuzumab/farmacocinéticaRESUMO
AIM: To assess the safety and tolerability of switching between subcutaneous (SC) and intravenous (IV) trastuzumab in the PrefHer study (NCT01401166). PATIENTS AND METHODS: Patients with HER2-positive early breast cancer completed (neo)adjuvant chemotherapy and were randomised to receive four cycles of SC trastuzumab, via single-use injection device (SID; Cohort 1) or hand-held syringe (Cohort 2), followed by four cycles of IV, or vice versa (the crossover period presented here) as part of their 18 standard cycles of adjuvant trastuzumab treatment. Adverse events (AEs) were reported using standard criteria. RESULTS: Overall, fewer AEs were reported during the IV treatment periods, regardless of administration sequence (IVâSC or SCâIV). Differences in AEs between the SC and IV periods were partly due to variances in grade 1 and 2 local injection site reactions (ISRs) and systemic administration-related reactions (ARRs) and these occurred mainly during SC treatment, as expected. When ISRs and ARRs were excluded, rates of AEs were higher during the first treatment period, compared with the second, in both treatment sequences; otherwise there was no clear pattern in the type of AEs reported. Rates of clinically important events, including grade ≥3 AEs, serious AEs, AEs leading to study drug discontinuation and cardiac AEs, were low and similar between treatment arms (<5%). There were no grade 4 or 5 AEs. No new safety signals for trastuzumab were observed. CONCLUSIONS: PrefHer revealed that switching from IV to SC trastuzumab (hand-held syringe or SID) or vice versa did not impact the known safety profile of trastuzumab.