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The combination showed tolerability and evidence of activity in non-BRCA carriers with advanced triple-negative breast cancer, suggesting the potential to expand the use of PARP inhibition beyond BRCA-mutant tumors
A phase Ib study recently published on Clinical Cancer Research shows promising results of alpesilib and olaparib association in patients with advanced triple-negative breast cancer without BRCA mutations: the combination is safe and has evidence of activity, with 59% of participants having disease control.
Authors have already reported data on the safety of olaparib, a PARP inhibitor, in combination of the PI3Ka-specific inhibitor alpelisib in patients with high-grade serous ovarian cancer; now they show new data of the study from a cohort of 17 patients with recurrent triple-negative breast cancer or recurrent breast cancer of any subtype with BRCA germline mutations and a median of three prior lines of chemotherapy. Patients were enrolled to a dose-escalation or dose-expansion cohort and results showed a good tolerability with hyperglycemia and rash as the most common treatment-related adverse events; the objective response rate was 18% and 59% of patients had disease control, with a median duration of response of 7.4 months. Results confirm previous experience with the combination of olaparib and the pan-PI3Ki inhibitor buparlisib in advanced high-grade serous ovarian cancer and triple-negative breast cancer (even though this combination induced more anxiety and depression in patients), showing that response was not restricted to patients with BRCA mutations; these new data suggests that the synergy of a combination of PARP inhibitors and a PI3Ka-specific inhibitor is safe, tolerable and effective and warrant further studies to explore PARP inhibitors beyond BRCA status. «It is attractive to consider the option of a targeted approach in a disease such triple-negative breast cancer, otherwise primarily treated with chemotherapy. Moreover, this combination uses oral agents that avoid toxicities associated with chemotherapy, including alopecia. Larger prospective randomized studies and biomarker development are planned to identify patients who are most likely to benefit from this all-oral combination», authors conclude.