AKT Inhibitor Plus Paclitaxel in Metastatic Triple-Negative Breast Cancer
Posted: Tuesday, February 25, 2020
According to results from the PAKT trial, the addition of the AKT inhibitor capivasertib to paclitaxel may improve progression-free as well as overall survival for some women with metastatic triple-negative breast cancer. According to Peter Schmid, MD, PhD, of the Barts Cancer Institute in London, and colleagues, there appeared to be more of a benefit seen with the combination therapy in patients who had PIK3CA/AKT1/PTEN-altered tumors. Their study results were published in the Journal of Clinical Oncology.
In this multicenter, double-blind, phase II trial, 140 women with previously untreated metastatic triple-negative breast cancer were randomly assigned to receive paclitaxel with capivasertib or placebo as first-line treatment. After a median follow-up of 18.2 months, the median progression-free survival was 5.9 and 4.2 months in the capivasertib/paclitaxel and placebo/paclitaxel groups, respectively; the median overall survival was 19.1 and 12.6 months. In patients who harbored tumors with PIK3CA/AKT1/PTEN alterations, the median progression-free survival was 9.3 months versus 3.7 months.
The most common grade ≥ 3 adverse events associated with the addition of capivasertib were diarrhea (13% vs. 1%), infection (4% vs. 1%), neutropenia (3% vs. 3%), rash (4% vs. 0%), and fatigue (4% vs. 0%). The safety and efficacy of capivasertib in this patient population will be further investigated in a planned phase III trial.
“On the basis of the current data, paclitaxel should be considered as the chemotherapy backbone for future studies, but other chemotherapy combinations may also be explored,” the authors concluded. “Prospectively planned biomarker analyses based on preclinical observations support selection of patients with PIK3CA/AKT1/PTEN alterations for future studies.”
Disclosure: For full disclosures of the study authors, visit ascopubs.org.