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Trastuzumab-Pertuzumab IV Admixture Demonstrates Safety, Tolerability


The LAVENDER study demonstrates safety and tolerability of simultaneous intravenous (IV) administration of biosimilar trastuzumab (Kanjinti) and pertuzumab in cohorts of healthy volunteers.

As clinical evidence accumulates on single-agent use of biosimilars in oncology and other settings, providers are also interested to know how these agents perform in combination with other therapies, where it may be possible to reduce costs of care with the introduction of biosimilar agents.

Trastuzumab reference product (RP; Herceptin) in combination with pertuzumab (Perjeta) has become standard of care for first-line treatment of stage II/III human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer. Overexpression of the protein HER2 is associated with cancer cell proliferation, and trastuzumab and pertuzumab bind to HER2 and suppress this growth.

In LAVENDER (N = 42), investigators compared simultaneous administration of trastuzumab biosimilar (Kanjinti; ABP 980) and pertuzumab vs trastuzumab RP plus pertuzumab, both administered via admixture in an intravenous (IV) bag.

As combination therapy of trastuzumab RP plus pertuzumab has become the standard of care for first-line treatment of late stage (stage II to stage III) HER2-positive metastatic breast cancer, an admixture of trastuzumab RP plus pertuzumab in a single 250 mL infusion bag is more efficient for patients and caregivers than 2 separate 250 mL infusions.

Use of an admixture of trastuzumab and pertuzumab is considered more efficient than administration of each drug through separate, consecutive infusions. Findings from LAVENDER published this month demonstrated safety and tolerability for ABP 980 and pertuzumab delivered from a single IV infusion bag, authors of the study wrote.

Healthy men were randomized 1:1 to IV pertuzumab 420 mg and ABP 980 6 mg/kg or an identical combination of trastuzumab RP and pertuzumab. The participants were followed for 92 days post dosing.

The resulting serum concentrations of the biosimilar and RP were comparable and there were no serious adverse events (AEs), deaths, or cardiac disorders, investigators said. No participants developed antidrug antibodies. “There were no notable differences between treatment groups in the severity of AEs and there were no events greater than grade 2 in severity,” they wrote.

The study was initiated with 42 enrollees, but a problem with air bubbles forming in IV lines caused the infusion pump to stop, which interrupted IV administrations for 5 of the first 6 enrollees. The problem was identified as being related to prior refrigeration of the agents and was solved by allowing the solutions to warm to room temperature (3 hours) prior to administration. The problem was not unique to either the biosimilar or RP admixture, study authors said.

Because of this event, data for the first 6 participants were not included in the final analysis, although the AE profile for these individuals was consistent with the main analysis. Data for 18 participants in each cohort were included in the assessment (n = 36).

Multiple prior studies have served as the foundation for LAVENDER.

In a 2010 study, trastuzumab RP and pertuzumab administered as sequential IV infusions demonstrated safety and tolerability in patients with metastatic HER2-positive breast cancer who had experienced disease progression during prior trastuzumab therapy. The objective response rate was 24.2% and the clinical benefit rate, a measure of complete response, partial response, and stable disease rates, was 50%.

In a study completed in 2013 (CLEOPATRA), patients received paclitaxel plus trastuzumab RP plus pertuzumab sequentially and intravenously. The 6-month progression-free survival rate was 86%, which was well above the minimum for success of 65%.

In the VELVET study, patients were administered vinorelbine in combination with trastuzumab RP and pertuzumab for the first-line treatment of HER2-positive breast cancer. This dosing was given both sequentially and via co-infusion (admixture) of trastuzumab and pertuzumab, followed by vinorelbine. There were no meaningful differences in outcome between the 2 cohorts, which LAVENDER authors said offered support for combining trastuzumab and pertuzumab in a single-bag infusion.

“The results of the LAVENDER study…demonstrate that administration of the biosimilar ABP 980 plus pertuzumab in a single 60-min IV infusion is safe and feasible,” the authors concluded. "The resulting [pharmacokinetics] of ABP 980 and trastuzumab RP were not affected by the co-infusion.”

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