One-of-a-Kind Combo Drug Provides a New Alternative for BRCA-Deficient Cancer Patients
A unique drug combination has elicited ground-breaking anti-tumour effects in patients with incurable BRCA-deficient cancers.
Recently, phase I data presented at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC revealed that two experimental drugs - sapacitabine and seliciclib – could produce an anti-tumour reaction in patients with incurable BRCA-deficient cancers. Sapacitabine causes single-strand damage to DNA, which can be repaired by BRCA proteins. Seliciclibincreases the probability of cancer cell death initiated by drugs like Sapacitabine. If this treatment is approved, it would be the first for this specific patient population.
This study involved 38 patients who possessed incurable solid tumours and satisfactory organs. Patients were given sapacitabine for seven days in conjunction with seliciclib for three days, both of which were taken twice daily. Initial findings included four patients with BRCA – deficient ovarian, pancreatic or breast cancer stating continuous partial responses to this drug combination.
Another three patients who experienced partial responses found that the treatment effects lasted for more than 78 weeks. Researchers in this study also observed stable disease for at least 12 weeks in about 8 patients, two of who had ovarian and breast cancers with a BRCA mutation. Their stable disease lasted for around 64 and 21 weeks, correspondingly.
Lead researcher and associate professor at the Dana-Farber Cancer Institute and Harvard Medical School in Boston, Geoffrey Shapiro said, “Initially in the dose-escalation phase of the trial, this combination produced stable disease of modest duration in some patients, which has been the experience with sapacitabine and CDK inhibitors in solid tumours.
However, other published research during the course of the study indicated the role of the homologous recombination pathway, dependent on BRCA proteins, for repair of sapacitabine-induced DNA damage. Additionally, the CDK proteins were implicated in DNA repair pathways. These findings prompted us to enroll patients with advanced cancer who had the BRCA mutation and led to the first partial responses and instances of durable stable disease.”
Following this initial phase of research, Shapiro and the other researchers continued to involve patients in this study. There are further schedules of this combination therapy to take place but these are currently under evaluation. Shapiro believes that if there is further evidence to confirm that a BRCA mutation status is a biomarker for response, then these drugs, whether individually or in combination with each other, should be investigated further within a larger group of patients.