Zanidatamab Plus Ibrance, Faslodex Show Promise in Advanced Breast Cancer

Treatment with bispecific antibody zanidatamab, the CDK4/6 inhibitor Ibrance (palbociclib) and the hormone therapy Faslodex (fulvestrant) had promising progression-free survival (PFS; the time a patient lives without their disease spreading or worsening) results and a manageable safety profile among patients with HER2-positive/HR-positive metastatic breast cancer (mBC) according to recent preliminary study findings.

By Aug. 3, 2023, 51 patients in a Phase 2a studywith a median age of 54 had received treatment with the drug trio. At a median follow-up of 16 months, the study’s primary endpoint of six-month progression-free survival (PFS) was 67%, or 34 patients, and was 69%, or 22 patients, among a subset of 32 patients who were ccHER2+, according to data presented as part of the 2023 San Antonio Breast Cancer Symposium.

“Zanidatamab, in combination with (Ibrance) and (Faslodex) demonstrated a promising PFS outcome, durable responses and a manageable safety profile in this heavily pretreated population. These results support further development of this novel chemotherapy-free regimen,” primary author Dr. Santiago Escrivá-de-Romaní, treating physician in medical oncology at Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron University Hospital in Barcelona, Catalonia, Spain, said during a presentation of the data at the symposium.

Patients with metastatic disease received a median of four prior systemic treatment regimens, four previous other HER2-targeted therapies and one previous endocrine therapy.

The median PFS was 12 months among all patients and 15 months among the ccHER2-positive subset. The median duration of response was 15 months for all patients and 14 months for patients in the ccHER2-positive subset.

Among all patients and the ccHER2-positive subset, disease control rates (patients whose disease shrunk, disappeared or stabilized) were 91% and 93%, respectively, and median durations of response were 15 months and 14 months.

Regarding patients with measurable disease — 46 total, 29 in the ccHER2-positive subset — the confirmed objective response rates (patients whose disease responded partially or completely to treatment) were 35% and 48%, respectively. For those same patients, the confirmed best objective responses occurred for three patients in each group who experienced a complete response, 13 and 11 patients who experienced a partial response and 26 and 13 patients who experienced stable disease, while four and two patients had progressive disease, respectively.

Participants in the trial had HER2-positive and HR-positive, unresectable, locally advanced or metastatic breast cancer, with an ECOG performance score of 0 or 1 (meaning they could perform daily tasks with little or no help) and had received prior treatment with at least the chemotherapy trastuzumab, the monoclonal antibody Perjeta (pertuzumab) and the antibody-drug conjugate Kadclya (trastuzumab emtansine) and had not been previously treated with a CDK4/6 inhibitor.

Treatment-related side effects experienced by more than 20% of patients included diarrhea (80%), neutrophil (a type of white blood cell) count decrease/neutropenia (59%), nausea (39%), stomatitis (swelling and sores inside the mouth; 37%), anemia (29%), vomiting (25%) and asthenia (fatigue; 24%).

Grade 3 or higher treatment-related side effects experienced by multiple patients included neutrophil count decrease/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (a low platelet count; 6%), hypokalemia (low potassium levels; 4%) and hypomagnesemia (4%; low magnesium levels), and one serious treatment-related side effect, increased transaminases, was also reported.

One patient discontinued all treatments due to grade 1 asthenia, two patients discontinued (Ibrance) due to adverse events (grade 3 diarrhea and grade 3 increase of transaminases) and four patients had dose reductions of zanidatamab due to adverse events. There were 14 deaths, though none were known to be related to treatment, with 12 due to disease progression, one due to COVID-19 and one unknown cause, with causality pending.

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