According to results from the phase 2 Neo-CheckRay trial, the addition of durvalumab and oleclumab to standard stereotactic body radiation therapy (SBRT) and neoadjuvant chemotherapy demonstrated promise among patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, high-risk early breast cancer. 

These results were first presented by Alex De Caluwé, MD, Jules Bordet Institute, Anderlecht, Belgium, at the 2024 European Society for Medical Oncology (ESMO) Congress in Barcelona, Spain. 

In this study, 135 patients were randomized on a 1-to-1-to-1 basis to receive neoadjuvant paclitaxel (once weekly for 12 weeks) with SBRT (3x8 Gy at week 5 targeting the primary tumor, avoiding lymph nodes and normal breast tissue) followed by dose-dense epirubicin and cyclophosphamide alone (n = 45) or with 1500 mg of durvalumab once every 4 weeks for 5 cycles (n =45), or with durvalumab in combination with 3000 mg of oleclumab once every 2 weeks for 4 cycles then once every 4 weeks for 3 cycles (n = 45). After surgical resection, patients received standard radiation and adjuvant endocrine therapy. The primary end point was residual cancer burden rate. Secondary end points included pathological complete response (pCR) rate, adverse events, and death incidences. 

At analysis, residual cancer burden rate was 37.8% in the control arm and 51.1% in both the durvalumab arm and in the durvalumab-oleclumab arm (P = .2031). The pCR rate was 17.8% in the control arm, 33.5% in the durvalumab arm, and 35.6% in the durvalumab-oleclumab arm (P = .565). Grade 3/4 treatment-related adverse events occurred in 27.1% of patients in the control arm, 64.7% of patients in the durvalumab arm, and 70.8% of patients in the durvalumab-oleclumab arm. The most common events included peripheral neuropathy, nausea, asthenia, anemia, diarrhea, fatigue, neutropenia, dysgeusia, and stomatitis. No treatment-related deaths occurred. 

As Dr De Caluwé concluded, “The trial demonstrated promising activity at surgery of the novel treatment combination…extensive ongoing translational research, including on-treatment biopsies one week after iSBRT, aims to better understand mechanisms of response and the contribution of oleclumab.” 

Source: 

De Caluwe A, Desmoulins I, Cao K, et al. Primary endpoint results of the Neo-CheckRay phase II trial evaluating stereotactic body radiation therapy (SBRT) +/- durvalumab (durva) +/- oleclumab (ole) combined with neo-adjuvant chemotherapy (NACT) for early-stage, high risk ER+/HER2- breast cancer (BC). Presented at 2024 ESMO Congress. September 13-17, 2024. Abstract LBA10