Flexible care in breast cancer

Wardley, Andrew M; Canon, Jean Luc; Elsten, L.; Murillo, C. Peña; Črnjević, Tanja Badovinac; Fredriksson, J.; Piccart, Martine

doi:10.1016/j.esmoop.2020.100007

Cited by 19 publications

(10 citation statements)

References 61 publications

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“…In addition, PH FDC SC provides healthcare professionals with the possibility of administering treatment in the patient’s home, as noted by the FDA [ 15 ]; an option that has become more important recently due to the COVID-19 pandemic. Home administration potentially reduces the risk of patients acquiring COVID-19 infection during hospital visits, a risk that could in turn lead to increased complications in patients with cancer [ 16 ]. The results further suggest that, in practice, no dose modifications are required according to covariates such as albumin, LBW, and race.…”

Section: Discussionmentioning

confidence: 99%

“…PH FDC SC for the first time combines two monoclonal antibodies in one vial and contains pertuzumab, trastuzumab, and recombinant human hyaluronidase (rHuPH20; an enzyme that temporarily degrades hyaluronan under the skin to aid in the dispersion and absorption of the antibodies) in a ready-to-use formulation. PH FDC SC demonstrates clear time-saving advantages compared with P + H IV, as well as other advantages over IV infusion such as less invasiveness, reduced pain, and improved convenience through at-home administration options (via a visiting healthcare professional) [14][15][16]. The approved SC formulation of trastuzumab has also been shown to have non-inferior serum trough concentrations (C trough ) and pathologic complete response (pCR) rates to IV trastuzumab, along with consistent long-term efficacy and a comparable safety profile [17][18][19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetic and exploratory exposure–response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

Wang¹,

Deng²,

Hennig

et al. 2021

Cancer Chemother Pharmacol

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Purpose To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure–response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure–efficacy and –safety relationships and support the approved SC dosing regimen. Methods Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Covariates were included from previously reported models. ER analysis was conducted using logistic regression. Results SC pertuzumab PK was described adequately by a two-compartment model with first-order absorption; significant covariates included in the final model were albumin, lean body weight, and Asian region; however, these appeared not to be clinically relevant. Trastuzumab concentrations were described adequately by the previous model; there was no evidence of a pertuzumab effect on trastuzumab PK as part of PH FDC SC and higher model-predicted pertuzumab exposure was not associated with differences in pathologic complete response rate or an increased probability of selected grade ≥ 3 adverse events of interest. Conclusion The approved PH FDC SC dose [loading: 1200/600 mg pertuzumab/trastuzumab (15 mL); maintenance: 600 mg pertuzumab/trastuzumab (10 mL) and 2000 U/mL recombinant human hyaluronidase every 3 weeks] provides a positive benefit–risk profile with comparable efficacy and safety to intravenous pertuzumab plus trastuzumab.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetic and exploratory exposure–response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

Wang¹,

Deng²,

Hennig

et al. 2021

Cancer Chemother Pharmacol

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“…A UK study demonstrated that home care for patients with cancer, patients with chronic conditions and those needing end-of-life care may benefit patients with regard to better adherence, reenablement, for example, resuming or continuing daily activities, improved quality of life, improved patient activation and financial savings [16]. The opportunity to move PH FDC SC administration by an HCP to the home was acknowledged by the FDA [9] and is particularly pertinent during the COVID-19 pandemic as a means of reducing the risk of infection associated with visiting hospitals (and the subsequent potential complications of COVID-19 infection in patients with cancer) [8]. An expanded access study (NCT04395508) is evaluating the safety of home-administered PH FDC SC by home health nurses.…”

Section: Discussionmentioning

confidence: 99%

“…It has w8 min loading and w5 min maintenance administration times and short observation times (minimum 30 and 15 min, respectively), giving patients convenience. Flexible care is an important consideration [8]; the FDA notes that PH FDC SC can be administered at home by a healthcare professional (HCP) [9]. PH FDC SC contains the same active ingredients as P þ H IV and is non-inferior in terms of P and H serum trough concentrations, with comparable pathological complete response (pCR) rates and safety profiles (FeDeriCa study) [10].…”

Section: Introductionmentioning

confidence: 99%

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

Fallowfield

Klingbiel

Messeri

et al. 2021

European Journal of Cancer

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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.

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“…14,[16][17][18][19][20][21][22][23][24][25][26][27][28][29] SC trastuzumab can be administered in the home or close to home as part of "flex care" treatment programs for patients with breast cancer. 30 Such programs are being developed or are ongoing in France, the UK, Belgium, Spain, and Italy. 22,23,[31][32][33][34][35][36][37][38] Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection PH FDC SC is a novel formulation that combines pertuzumab plus trastuzumab with rHuPH20 in one ready-to-use, fixed-dose combination vial for the treatment of HER2-positive breast cancer.…”

Section: Recombinant Human Hyaluronidase As a Permeation Enhancermentioning

confidence: 99%

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach

DuMond

Patel

Gross

et al. 2021

J Oncol Pharm Pract

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Pertuzumab plus trastuzumab, administered intravenously (IV) with chemotherapy, is standard treatment for HER2-positive metastatic or high-risk early breast cancer. Pertuzumab and trastuzumab are administered over 1–2.5 h traditionally; however, the need for IV infusions places a strain on medical centers with respect to scheduling, preparation, and administration. A novel fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PHESGO®, PH FDC SC) can be administered in approximately 5–8 min. PH FDC SC was non-inferior to IV pertuzumab plus trastuzumab in terms of pertuzumab and trastuzumab serum levels in the phase III FeDeriCa study, which enrolled 500 patients with HER2-positive early breast cancer. Total pathologic complete response rates were comparable after PH FDC SC (59.7%) or IV pertuzumab plus trastuzumab (59.5%), as was the incidence of grade ≥3 (48.8% vs 52.8%) and serious adverse events (16.1% vs 17.9%). The results of a phase II clinical trial (PHranceSCa) showed that a majority of patients (85%) preferred PH FDC SC treatment over IV pertuzumab plus trastuzumab. A US multicenter expanded access study (NCT04395508) is evaluating the safety of PH FDC SC administered at home by nurse providers in patients receiving maintenance HER2-targeted therapy every 3 weeks. This product takes much less time to administer than IV pertuzumab–trastuzumab and has the potential to alleviate time constraints for patients and busy clinics. In this review we provide an overview of PH FDC SC, and discuss our experience in preparing and administering this product to patients with HER2-positive breast cancer during clinical trials.

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Flexible care in breast cancer

Cited by 19 publications

References 61 publications

Population pharmacokinetic and exploratory exposure–response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

Population pharmacokinetic and exploratory exposure–response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study

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

Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive breast cancer: A multidisciplinary approach

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