Zanidatamab Plus Palbociclib, Fulvestrant Shows Promising PFS in HER2+/HR+ mBC


Preliminary study results examining the bispecific antibody, CDK4/6 inhibitor, and hormone therapy combination in patients with advanced breast cancer were presented at SABCS.

3d rendered medically accurate illustration of a breast cancer: © SciePro -

3d rendered medically accurate illustration of a breast cancer: © SciePro -

Treatment with bispecific antibody zanidatamab, CDK4/6 inhibitor palbociclib (Ibrance), and the hormone therapy fulvestrant (Faslodex) had promising progression-free survival (PFS) results and a manageable safety profile among patients with HER2-positive/hormone receptor (HR)-positive metastatic breast cancer (mBC) according to recent preliminary study findings.

By Aug. 3, 2023, 51 patients in a multicenter, Phase 2a study (NCT04224272) with a median age of 54 years (range, 36-77) had received treatment with the drug trio, and at a median follow-up of 16 months (range, 2-32) the study’s primary endpoint of six-month progression-free survival (PFS) was 67%, or 34 patients and 69%, or 22 patients, among a subset of 32 patients who were ccHER2–positive, according to data presented as part of the 2023 San Antonio Breast Cancer Symposium.1

“Zanidatamab, in combination with palbociclib and fulvestrant 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 Santiago Escrivá-de-Romaní, MD, 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 4 (range, 1-12) prior systemic treatment regimens, 4 (range, 2-6) previous other HER2-targeted therapies, and 1 (range, 0-5) previous endocrine therapy.

The median PFS was 12 months (95% CI, 8-15) among all patients and 15 months (95% CI, 9-17) among the ccHER2-positive subset. The median duration of response was 15 months (95% CI, 12-25) for all patients and 14 months (95% CI, 11-25) for patients in the ccHER2-positive subset.

Among all patients and the ccHER2-positive subset, disease control rates were 91% (95% CI; 79-98) and 93% (95% CI; 77-99), respectively, and median durations of response were 15 months (95% CI; 12-25) and 14 months (range, 11-25).

Regarding patients with measurable disease — 46 total, 29 in the ccHER2-positive subset—the confirmed objective response rates were 35% (95% CI; 21-50) and 48% (95% CI; 29%-68%), respectively. For those same patients, the confirmed best objective responses occurred for 3 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 4 and 2 patients experienced progressive disease, respectively.

Among the 29 patients with available PAM50 subtyping, the PFS6 rate was 66%, and the median PFS was 9 months (95% CI; 7-14).

Participants in the trial had HER2-positive or HR-positive, unresectable, locally advanced or metastatic breast cancer, with an ECOG performance score of 0 or 1 and had received prior treatment with at least trastuzumab, pertuzumab (Perjeta), and the antibody-drug conjugate trastuzumab emtansine (Kadclya) and had not been previously treated with a CDK4/6 inhibitor.

Treatment-related adverse events (TRAEs) experienced by more than 20% of patients included diarrhea (80%), neutrophil count decrease/neutropenia (59%), nausea (39%), stomatitis (37%), anemia (29%), vomiting (25%), and asthenia (24%).

Grade 3 or higher TRAEs experienced by multiple patients included neutrophil count decrease/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (6%), hypokalemia (4%), and hypomagnesemia (4%), and one serious TRAE, increased transaminases, was also reported.

One patient discontinued all treatments due to grade 1 asthenia, 2 patients discontinued palbociclib due to AEs (grade 3 diarrhea and grade 3 increase of transaminases), and 4 patients had dose reductions of zanidatamab due to AEs. There were 14 deaths, although none were known to be related to treatment, with 12 due to disease progression, 1 due to COVID-19, and 1 unknown cause, with causality pending.

Escrivá-de-Romani S, Cejalvo JM, Alba E, et al. Primary results from a phase 2a study of zanidatamab (zani) + palbociclib (palbo) + fulvestrant (fulv) in HER2+/HR+ metastatic breast cancer (mBC). Presented at: 2023 San Antonio Breast Cancer Symposium; December 5-9, 2023; San Antonio, TX. Abstract LBO1-04
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