The addition of ipatasertib to paclitaxel in patients with PIK3CA/AKT1/PTEN-altered hormone receptor–positive, HER2-negative advanced breast cancer did not improve survival.- Genentech/Roche

Improvement in progression-free survival (PFS) and objective response rate (ORR) was not observed with the addition of ipatasertib from Genentech/Roche to paclitaxel in patients with PIK3CA/AKT1/PTEN-altered hormone receptor–positive, HER2-negative advanced breast cancer , missing the primary and secondary end points of the phase III IPATunity130 trial for which results were presented during the 2020 European Society of Medical Oncology (ESMO) Virtual Congress. At a median follow-up of 12.9 months, the investigator-assessed PFS was 9.3 months with the combination (95% CI, 8.0-11.0) versus 9.3 months with placebo/paclitaxel (95% CI, 7.2-12.2), failing to meet the primary end point of the study (HR, 1.00; 95% CI, 0.71-1.40; log-rank P = .9965). “The results are consistent with the phase 1/2IIBEECH trial of paclitaxel with or without the AKT inhibitor capivasertib,” said Nicholas Turner, PhD, lead study author and consultant medical oncologist at The Royal Marsden Hospital, in a virtual presentation of the data. “In contrast, an AKT inhibitor in combination with fulvestrant improved PFS in the phase 2 FAKTION trial, suggesting that endocrine blockade is critical to the activity of AKT inhibitors in hormone receptor–positive breast cancer.” The PI3K/AKT pathway plays a critical role in HR–positive, HER2-negative breast cancer, and AKT activation is responsible for resistance to endocrine therapy.