Administration of Phesgo into the Abdominal Wall

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

This article responds to your request for information on administration of Phesgo® (pertuzumab, trastuzumab, and hyaluronidase) into the abdominal wall.

 

This response was developed according to principles of evidence-based medicine and contains data from a Phase 3 study.

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Last updated December 03, 2023

Summary

  • Phesgo is administered into the thigh by SC injection.
    • There are no data on Phesgo injections administered at sites other than the thigh. However, there are data on the administration of Herceptin SC into the abdominal wall.
      • The GAIN-2 substudy evaluated the PK, patient preference, and safety of Herceptin SC administered into the thigh versus the abdominal wall.
        • Bioavailability was approximately 30% higher following SC administration into the thigh compared to the abdominal wall.
          • Any grade and grade 3-4 treatment-related AEs were comparable between the two administration sites.

          Abbreviations

          AE=adverse event

          AUC0-21d=area under the plasma-concentration time curve from 0-21 days

          CI=confidence interval

          Cmax=peak plasma concentration

          Ctrough=trough plasma concentration

          mITT=modified intention-to-treat

          PK=pharmacokinetics

          SC=subcutaneous

          SD=standard deviation

          Tmax=time to peak drug concentration

          Phesgo is a ready-to-use fixed-dose combination of pertuzumab, trastuzumab, and recombinant human hyaluronidase administered in the thigh by SC injection using a needle and syringe.‎[1] Recombinant human hyaluronidase is an enzyme that increases the dispersion and absorption of co-administered drugs when administered subcutaneously.[2]

          Clinical experience of administering Phesgo into the abdominal wall

          There are no data on Phesgo injections administered at sites other than the thigh. However, there are data on the administration of Herceptin SC into the abdominal wall.[3] Herceptin SC ™ is a formulation which also contains trastuzumab and recombinant human hyaluronidase, and is also administered by SC injection into the thigh.[4]

          Clinical experience of administering Herceptin SC into the abdominal wall

          GAIN-2 substudy evaluating administration of Herceptin SC into the abdominal wall

          A substudy of the multicentre, randomised, Phase 3 GAIN-2 study evaluated the PK, safety, and patient preference of Herceptin SC when administered into the thigh versus the abdominal wall.[3] The mITT group included 219 patients, 110 in the thigh group and 109 in the abdominal wall group.

          PK results comparing administration in the thigh to the abdominal wall

          PK details were assessed in a pre-determined subset of 30 patients: 17 in the thigh group and 13 in the abdominal wall group.[3] Bioavailability was found to be approximately 30% higher following SC administration into the thigh compared to the abdominal wall.

          Variability for Cmax, AUC0-21d, and Ctrough was also higher following administration into the abdominal wall than into the thigh.[3] Tmax was not significantly different between the two groups.

          Figure 1 depicts the difference in mean plasma concentration over time between the two administration locations. A summary of various PK parameters is presented in Table 1.

          Figure 1. Mean plasma concentration-time profiles of Herceptin SC administered into the thigh and abdominal wall [3]

          Mean plasma concentration-time profiles of Herceptin SC administered into the thigh and abdominal wall

          Table 1. Comparison of PK parameters for the thigh group compared to the abdominal wall group [3]

          Parameter in Cmax (µg/mL), AUC0-21d (µg/mL), Ctrough (µg/mL), Tmax (days) and Mean (SD) and Geometric Mean Ratio(90% CI)

          Safety results for the mITT group

          Safety was evaluated in the 219 patients in the mITT group.[3] Pain (p=0.01) and irritation around the injection site (p=0.033) was more commonly reported in patient interviews in the thigh group compared to the abdominal wall group.

          The number of patients experiencing any grade and grade 3-4 treatment related AEs was comparable between injection sites.[3] The number of local site reactions did not differ significantly between sites.

            

          Table 2. Summary of safety results for the mITT group [3]

          AEs for Any AE All grades Grade 3-4, Local site reactions All grades and Thigh(N=110), Abdominal Wall(N=109) and p-value

          References

          1. Tan A, Im S, Mattar A, et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study. Lancet Oncol 2021;22:85-97. https://www.ncbi.nlm.nih.gov/pubmed/33357420
            1. Roche Internal Regulatory Report (Herceptin CDS v.21). Accessed 1 Sep 23.
              1. Reinisch M, Untch M, Mahlberg R, et al. Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study. Breast 2022;66:110-117. https://www.ncbi.nlm.nih.gov/pubmed/36223695
                1. Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of (neo)adjuvant trastuzumab in patients with HER2-positive, clinical stage I-III breast cancer (HannaH study): a phase 3, open-label, multicentre, randomised trial. Lancet Oncol 2012;13:869-78. https://www.ncbi.nlm.nih.gov/pubmed/22884505

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