Neoadjuvant triple blockade of HER2, the estrogen receptor (ER), and RB1 with trastuzumab, pertuzumab, fulvestrant, and palbociclib may be an effective chemotherapy-free regimen for women with HER2-positive, ER-positive breast cancer, according to a study published in Lancet Oncology.1
For the open-label phase 2 NA-PHER2 study (ClinicalTrials.gov Identifier: NCT02530424), researchers evaluated the outcomes of 30 treatment-naive patients with HER2-positive, ER-positive breast cancer who received neoadjuvant intravenous trastuzumab and pertuzumab, oral palbociclib, and intramuscular fulvestrant. The primary endpoints were change in Ki67 expression (a biomarker indicative of cellular proliferation) from baseline to 2 weeks of treatment and to surgery, and change in apoptosis rate from baseline to surgery.
Of the 30 patients, 25 had invasive cancer cells in tissue samples evaluable for Ki67 expression. Baseline geometric mean Ki67 expression was 31.9 compared with 4.3 at week 2 (P < .0001) and 12.1 at time of surgery (P = .013). The geometric mean for apoptosis was 1.2 vs 0.4 (P = .019) at baseline vs at surgery, respectively.
A clinical objective response was noted in 95% (29) of patients prior to surgery (95% CI, 83%-100%), and 27% (8) of patients had a pathological complete response in the breast and axillary nodes.
The most frequently reported grade 3 adverse events included neutropenia, diarrhea, stomatitis, elevated alanine aminotransferase, and hypersensitivity reactions; no grade 4 or worse adverse events were observed.
The authors concluded that “further clinical testing and additional molecular characterization is necessary, not only in hormone receptor-positive tumours but also in tumours without HER2 amplification.”
- Gianni L, Bisagni G, Colleoni M, et al. Neoadjuvant treatment with trastuzumab and pertuzumab plus palbociclib and fulvestrant in HER2-positive, ER-positive breast cancer (NA-PHER2): an exploratory, open-label, phase 2 study. Lancet Oncol. 2018 Jan 8. doi: 10.1016/S1470-2045(18)30001-9 [Epub ahead of print]