Chemo-free triplet regimen shows antitumour activity in HR+, HER2+ breast cancer

Treatment with the combination of zanidatamab plus palbociclib and fulvestrant is safe and demonstrates promising antitumour activity in patients with HR-positive, HER2-positive advanced or metastatic breast cancer, according to a phase IIa study.

The two-part study included adults who had pathologically confirmed unresectable or metastatic breast cancer, were assessed locally to be HR-positive and HER2-positive, had an ECOG performance status of 0 or 1, and had disease progression during or after previous HER2-targeted therapies.

In part 1, patients received starting doses of zanidatamab (20 mg/kg intravenously once every 2 weeks on days 1 and 15 of a 28-day cycle) with palbociclib (125 mg orally once a day on days 1–21 of each cycle) and fulvestrant (500 mg intramuscular injection once every 2 weeks for the first three doses [cycle 1: days 1 and 15, cycle 2: day 1], then once every 4 weeks [all subsequent cycles: day 1]). Safety of the triplet combination was assessed, and the recommended doses for part 2 were confirmed.

In part 2, patients were given the recommended doses confirmed in part 1. The primary endpoint was progression-free survival (PFS) at 6 months. Safety and PFS were evaluated in all enrolled patients who received any dose of zanidatamab, palbociclib, or fulvestrant. Patients treated at the recommended doses in part 1 were analysed together with the patients in part 2.

A total of 51 patients (median age 54.0 years, 96 percent female, 82 percent White) participated in the study, including eight in part 1 and 43 in part 2. The median follow-up was 16.1 months, and the median duration of triplet regimen treatment was 7.4 months. The patients had previously received a median of four HER2-targeted therapies, including 12 who had previously received trastuzumab deruxtecan.

All 51 patients received treatment at the recommended doses, and all of them had at least one treatment-related adverse event (TRAE) of any grade, with the most common being diarrhoea (80 percent). Thirty-four patients (67 percent) had grade 3 or 4 TRAEs (67 percent), the most common of which was neutropenia (51 percent). One patient (2 percent) had a serious grade 3 TRAE of increased transaminases. No treatment-related deaths were documented during the study.

The PFS rate at 6 months was 66.7 percent (95 percent confidence interval, 52.1–79.2).