Zanidatamab plus palbociclib, fulvestrant shows promising PFS in HER2+/HR+ mBC

Based on recent preliminary study resultsUsing the bispecific antibody zanidatamab, a CDK4/6 inhibitor, in patients with HER2-positive/hormone receptor (HR)-positive metastatic breast cancer (mBC) Treatment with Palbociclib and the hormone therapy fulvestrant (Faslodex) has promising progression-free survival (PFS) results and a manageable safety profile. As of August 2023, in a multicenter, phase 2a study (NCT04224272), 51 patients with a median age of 54 years (range, 36-77 years) received triple therapy at a median follow-up of At 16 months (range 2-32 months), the study's primary endpoint of 6-month progression-free survival (PFS) was 67% in 34 patients and 69% in 22 of 32 ccHER2-positive patients.

Patients with metastatic disease had received a median of4 (range, 1-12) prior systemic treatment regimens, 4 (range, 2-6) prior other HER2-targeted therapies, and 1 (range, 0-5) prior endocrine therapy. Median PFS was 12 months (95% CI, 8-15) for all patients and 15 months (95% CI, 9-17) for the ccHER2-positive subgroup. The median duration of response was 15 months (95% CI, 12-25) for all patients and 14 months (95% CI, 11-25) for ccHER2-positive patients. Across all patients and in the ccHER2-positive subpopulation, disease control rates were 91% (95% CI; 79-98) and 93% (95% CI, 77-99), and the median duration of response was 15 months (95% CI: 12-25) and 14 months (range: 11-25).

Regarding patients with measurable disease, a total of 46 patients, 29 of whom were ccHER2-positive patients - confirmed objective response rates of 35% (95% CI; 21-50) and 48% (95% CI: 29%-68%). For these same patients, 3 patients in each group experienced a complete response, 13 and 11 patients experienced a partial response, 26 and 13 patients experienced stable disease, and 4 and 2 patients experienced progressive disease, respectively. Among 29 patients with available PAM50 classification, 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, an ECOG performance score of 0 or 1, and had at least one prior treatment with trastuzumab, palbociclib, and the antibody-drug conjugate trastuzumab emtansine, and no prior treatment with a CDK4/6 inhibitor.

ExceedsTreatment-related adverse events (TRAEs) experienced by 20% of patients included diarrhea (80%), neutropenia/neutropenia (59%), nausea (39%), stomatitis (37%), anemia (29%), vomiting (25%), and fatigue (24%). Grade 3 or higher TRAEs experienced by multiple patients included neutropenia/neutropenia (53%), diarrhea (14%), anemia (10%), thrombocytopenia (6%), hypokalemia, and hypomagnesemia (4%). One serious TRAE, elevated transaminases, was also reported. One patient discontinued all treatment due to grade 1 fatigue, 2 patients discontinued palbociclib treatment due to AEs (grade 3 diarrhea and grade 3 aminotransferase elevation), and 4 patients had zanidatamab dose reductions due to AEs. There have been 14 deaths, although none are known to be related to treatment, 12 due to disease progression, one due to COVID-19, and one of unknown cause, with causality pending.

PalbociclibThe original drug has been launched in China and has been included in medical insurance. Currently, reimbursement is only available to patients who meet the indications. The common specifications100mg*21 pills may cost more than 6,000 yuan per box, while the original drug sold overseas is more expensive. The price of 125mg*21 pills per box may be around 10,000 yuan (the price may fluctuate due to exchange rates). Palbociclib generics are also sold overseas. The ingredients of the drug are basically the same as those sold domestically and abroad, but the price is cheap. For example, the price of a box of 125mg*21 tablets produced by a Bangladesh pharmaceutical factory may be several hundred yuan (the price may fluctuate due to the exchange rate).