Selecting patients with oligo-metastatic breast cancer harboring homologous recombination deficiency (HRD) for intensified chemotherapy: The OLIGO-study

Abstract

Background: About 5% of patients with metastatic breast cancer (MBC) survive more than 10 years. Long-term survival is mostly seen in patients with limited, maximum of 3-5, distant metastases, often referred to as 'oligo'-MBC. Oligo-metastatic cancer can be treated with curative intent using a multidisciplinary approach that targets the detected metastases, circulating micro-metastases, and any locoregional disease if present. Optimal patient selection is of vital importance. Intensified chemotherapy in the treatment of breast cancer is controversial, as older studies have not shown a survival benefit in unselected patients. Recent retrospective analyses, however, have suggested that patients with HRD derive significant benefit from intensified chemotherapy compared to conventional chemotherapy. Trial design: This study will evaluate the difference in event-free survival (EFS) between intensified chemotherapy and conventional chemotherapy as part of a multimodality treatment approach in patients with oligo-MBC harboring HRD. Patients are eligible if they have pathological proven oligo-MBC, defined as 1-3 distant metastases, either as de novo or recurrence for which no chemotherapy is given. All lesions must be amenable to surgery or radiotherapy with curative intent. No progression on induction chemotherapy is allowed. Lastly, the tumor has to be HRD by array comparative genomic hybridization. Patients start with 3 cycles of induction chemotherapy, which includes anthracyclines and taxanes in treatment-naïve patients and is adapted according to previously received (neo)adjuvant treatment in others. Patients are 1:1 randomized to another 3 cycles of conventional chemotherapy or 2 cycles of intensified chemotherapy (carboplatin, thiotepa and cyclophosphamide) with stem cell support. Following systemic treatment, all patients receive maximal surgery and/or radiotherapy of locoregional and distant disease. The primary endpoint is EFS at 3 years. Toxicity, time to progression, and overall survival are secondary clinical endpoints. In total 86 patients are required. At the time of abstract submission, 33 patients were randomized.