In a German phase II trial (WSG-KEYRICHED-1) reported in The Lancet Oncology, Kuemmel et al evaluated whether chemotherapy-free neoadjuvant therapy with pembrolizumab plus trastuzumab/pertuzumab showed activity in patients with HER2-enriched early breast cancer.
As stated by the investigators: “Accumulating evidence indicates that about 30% to 40% of patients with HER2-positive early breast cancer might achieve excellent outcomes without chemotherapy. Therefore, we aimed to test the pathological complete response after the addition of pembrolizumab to dual anti-HER2 blockade and omission of chemotherapy in patients with HER2-enriched breast cancer.”
Study Details
In the multicenter open-label trial, 43 evaluable women with previously untreated clinical stage T1c–T3, N0–N2, M0, primary unilateral early invasive breast cancer, HER2 immunohistochemistry score 2+ or 3+ status, and any hormone receptor status were enrolled between September 2020 and May 2021. Patients received four cycles of pembrolizumab at 200 mg every 3 weeks for 12 weeks, trastuzumab biosimilar ABP 980 at an 8-mg/kg loading dose then 6 mg/kg every 3 weeks for 12 weeks, and pertuzumab at an 840-mg loading dose then 420 mg every 3 weeks for 12 weeks. The primary endpoint was proportion of patients with pathologic complete response (ypN0 or ypT0/is); for the primary endpoint to be met, the lower bound of the one-sided 95% confidence interval had to exceed 40% with statistical significance.
Key Findings
Median follow-up was 8.6 months (interquartile range = 8.3–9.0 months).
Pathologic complete response on central assessment was observed in 20 of 43 patients (47%). The lower bound of the one-sided 95% confidence interval was 33% (P = .22); thus, the null hypothesis could not be rejected.
Among 48 patients in the safety population, grade 3 or 4 treatment-related adverse events occurred in 4 patients (8%), including increased alanine aminotransferase, drug hypersensitivity, nephritis, and panic attack in 1 patient each. Serious adverse events occurred in 8%, including drug hypersensitivity, panic attack, pyrexia, and COVID-19 infection in 1 patient each. Pembrolizumab was discontinued or interrupted due to adverse events in three patients (6%). No deaths were observed.
The investigators concluded: “Although the null hypothesis could not be rejected, the WSG-KEYRICHED-1 trial highlights the potential of a short chemotherapy-free combination of pembrolizumab with dual anti-HER2 therapy, warranting the initiation of randomised trials investigating the immunotherapy without chemotherapy in patients with HER2-enriched breast cancer.”
Sherko Kuemmel, MD, of the Breast Unit, Clinics Essen-Mitte, Essen, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Merck Sharp & Dohme and NanoString Technologies. For full disclosures of all study authors, visit The Lancet Oncology.
