Herceptin Hylecta (trastuzumab/hyaluronidase-oysk)

P2; Active, not recruiting --> Completed

P2, N=40, Recruiting, Adrienne G. Waks | Initiation date: Apr 2024 --> Nov 2023

Subcutaneous trastuzumab or trastuzumab biosimilars do not pose a greater risk of infusion-related reactions compared to intravenous trastuzumab and may offer more affordable treatment options for breast cancer patients who qualify for trastuzumab therapy.

P2, N=40, Recruiting, Adrienne G. Waks | Not yet recruiting --> Recruiting

SC trastuzumab induced relevant sTILs enrichment, with favorable variations of immune parameters in HER2-positive BC pts with RD after NAT. Novel immunotherapy strategies should be tested to achieve SC-specific, antitumor immune response.

P2, N=40, Not yet recruiting, Adrienne G. Waks

P2; Recruiting --> Active, not recruiting | Trial completion date: Aug 2023 --> Dec 2023 | Trial primary completion date: Aug 2023 --> Dec 2023

For patients and caregivers, the treatment time per cycle was 91% less than IV administrations, leading to total savings of CNY 19,681 per patient in terms of direct cost and productivity cost over a full course of treatment. Conclusions Besides saving time for HCPs and patients, trastuzumab SC can help optimize treatment process, improve overall quality and efficiency of healthcare system & hospital management, aligned with China policies of high-quality hospital development.

All patients received 4 cycles of docetaxel + Herceptin SC. Conclusions The study met its primary endpoint with pCR rate of 53% and manageable toxicity. To our knowledge, this is the first investigator initiated multi-institutional biomarker driven oncology clinical trial ever conducted in sub-Sahara Africa, paving the way for future pragmatic patient-centric biomarker informed clinical trials in populations of African Ancestry.

The safety was consistent with the known H-IV and H-SC profiles without any safety concern raised over a prolonged exposure to H-SC.

Combination of SC trastuzumab and intravenous pertuzumab for HER2-positive breast cancer is a safe and well-tolerated option in adjuvant setting.

The subcutaneous formulation of trastuzumab is a potential cost-saving therapy for HER2-positive breast cancer patients in Hong Kong. The drug acquisition cost was the parameter with the greatest effect on the total cost of treatment.

Neoadjuvant trastuzumab (SC) and pertuzumab plus chemotherapy for HER2+ early-stage BC showed benefits in a real-life setting, with an acceptable safety profile.

P2, N=56, Active, not recruiting, Merck Sharp & Dohme LLC | Recruiting --> Active, not recruiting | Trial primary completion date: Jan 2024 --> Jul 2023

Subcutaneous trastuzumab into the thigh showed an approximately 30% higher bioavailability. Injections were well tolerated and preferred over intravenous administration. The subcutaneous injection into the thigh should remain the standard of care.

Those with incomplete clinical response by breast ultrasound volume measurements receive 3 additional cycles of chemotherapy; cyclophosphamide 600mg/m2, epirubicin 90mg/m2 and 5-fluorouracil 600mg/m2 every 3 weeks before re-evaluation for surgery...Secondary objectives are to evaluate invasive disease-free survival (iDFS), the pattern of response and mechanisms of resistance to treatment based on genomic markers, the pharmacokinetics of Herceptin SC, quality of life, and adverse event rates, including cardiac toxicity...More protocol details can be found at ClinicalTRial.gov NCT03879577 and JCO Glob Oncol2020 doi: 10.1200/GO.20.00043 Progress: The study has met its primary endpoint and will be closed to accrual by the time of the meeting. Results will be submitting as Late Breaking before the meeting

Trastuzumab biosimilars are ultimately preferred by a proportion of patients, especially in cases where co-administration of other chemotherapeutic agents, such as trastuzumab and tucatinib, a small molecule of tyrosine kinase inhibitor, is required in patients with HER-positive metastatic breast cancer...Further cost-effectiveness analyses will be very important, along with expectations regarding successful concomitant subcutaneous administration of trastuzumab with other anticancer drugs, such as pertuzumab. This systematic review describes and analyzes the so-far published studies concerning the use of the available trastuzumab biosimilars in HER-positive early and metastatic breast cancer in terms of efficacy, safety, and cost-benefit ratio. An attempt was also made to draw some conclusions and to comment on future needs and perspectives.

P2, N=462, Active, not recruiting, Borstkanker Onderzoek Groep | Trial primary completion date: May 2022 --> Nov 2022

The 5-year follow-up analysis of the SafeHER trial demonstrating that SC trastuzumab has an acceptable safety profile, including cardiac toxicity, and efficacy for the treatment of HER2-positive EBC with and without chemotherapy, corresponding with historical data with trastuzumab.

P2, N=56, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Jan 2023 --> Jan 2024

Those with incomplete clinical response by breast ultrasound volume measurements receive 3 additional cycles of chemotherapy; cyclophosphamide 600mg/m2, epirubicin 90mg/m2 and 5-fluorouracil 600mg/m2 every 3 weeks before re-evaluation for surgery...Secondary objectives are to evaluate invasive disease-free survival (iDFS), the pattern of response and mechanisms of resistance to treatment based on genomic markers, the pharmacokinetics of Herceptin SC, quality of life, and adverse event rates, including cardiac toxicity...Progress: Accrual commenced on 3rd April 2020 and is 75% completed. To date, monitoring, regulatory, as well as Data Safety and Monitoring Board progress evaluation did not identify any logistical or safety issues such as underdeveloped infrastructure, unacceptable rate of non-compliance with study protocol, poor informed consent procedure or serious adverse events to warrant stopping the trial.

The recommended phase II dose of varlitinib with paclitaxel is 300 mg twice daily intermittently dosed. This is active in HER2+ metastatic breast cancer. Subcutaneous trastuzumab can be added safely to varlitinib and paclitaxel. This combination is currently being evaluated as neoadjuvant therapy in HER2+ breast cancer (NCT02396108).

P2; N=232 --> 102 | Trial completion date: Dec 2021 --> Aug 2023 | Trial primary completion date: Sep 2021 --> Aug 2023

SC trastuzumab was widely acceptable to both patients and HCPs. The safety and tolerability of SC trastuzumab was consistent with the known safety profile of SC and IV administration.

The use of TZM-SC is recommended, in the scenario of a lower cost of the drug and a shorter duration of administration time. Especially in a country with low funding, which only allows subsidizing the direct costs of cancer treatment.

P2, N=90, Recruiting, Centre Leon Berard | Trial completion date: Nov 2021 --> Apr 2022 | Trial primary completion date: Nov 2021 --> Apr 2022

P2, N=462, Active, not recruiting, Borstkanker Onderzoek Groep | Recruiting --> Active, not recruiting | Trial completion date: Feb 2032 --> May 2032

Currently, TCHP (docetaxel + carboplatin + trastuzumab + pertuzumab) regimen are used commonly with the highest pCR rate caused by double HER2 blockade (pCR rate: 60-70%). Neoadjuvant TAHP regimen is a feasible and active treatment option in HER2-positive early breast cancer showing high pCR rate and modest toxicity.

Half of pts (n=64, 50.7%) were treated in the neoadjuvant setting with chemothera- py, pertuzumab and EV T. Patient preference was the main reason to consider EV or SC route. These data are of major relevance in current pandemic context, suggesting that reevaluation period can be omitted. Moreover our analysis did not show a significant impact of BMI on ISRs in HER2+ EBC pts treated with SC T.

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.

P2, N=500, Recruiting, Dana-Farber Cancer Institute | Not yet recruiting --> Recruiting | Initiation date: Nov 2021 --> Jun 2021

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.

Differences in healthcare costs between intravenous biosimilar trastuzumab and subcutaneous reference trastuzumab depended on the level of discounts on these formulations and on intravenous vial sharing. Our case study demonstrates that comparing costs of intravenous vs. subcutaneous formulations is complex and multifactorial, and entails more than a simple cost comparison of products.

No new AEs were observed. The 1-year iDFS was 90% (95% CI 0.656 to 0.974) Combination of SC trastuzumab and intravenous pertuzumab for HER2-positive breast cancer is a safe and well-tolerated option in adjuvant setting.

P2, N=500, Not yet recruiting, Dana-Farber Cancer Institute

In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy. The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.

Our study shows a more favorable safety profile of s.c. versus i.v trastuzumab administration. The use of s.c. trastuzumab could be advisable in at-risk patients.

P2, N=56, Recruiting, Merck Sharp & Dohme Corp. | Not yet recruiting --> Recruiting

Safety and efficacy with subcutaneous trastuzumab plus intravenous pertuzumab and docetaxel in mBC are consistent with historical evidence of intravenous trastuzumab with this combination. Findings further support subcutaneous administration not affecting safety/efficacy profiles of trastuzumab in HER2-positive BC with increased flexibility in patient care. A fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection has recently been approved for the treatment of HER2-positive early/mBC, further addressing the increasing relevance of and need for patient-centric treatment strategies.

Of the 2573 patients in the intent to treat (ITT) population, 1819 (70.7%) completed the 5-year FU; 754 patients (29.3%) discontinued early, mostly due to disease progression/recurrence (41.5%). In the safety population (n = 2569), AEs occurred in 2334 patients (90.9%) during the whole study, and related AEs occurred in 1259 patients (49.0%). 905 patients (35.2%) reported AEs in the FU period (Table 1).

Concurrent with the development of SC trastuzumab, IV trastuzumab biosimilars comprise another treatment option that, in view of their reduced cost, might improve patient access and increase cost-effectiveness for healthcare providers and payers. In this review, we seek to raise awareness of the current options available for trastuzumab so that healthcare providers can optimally treat patients according to their individual situations and preferences.

P3, N=166, Completed, Spanish Breast Cancer Research Group | Active, not recruiting --> Completed