Phase Iii Study Of Palbociclib Combined With Endocrine Therapy In Patients With Hormone Receptor-Positive, Her2-Negative Primary Breast Cancer And With High Relapse Risk After Neoadjuvant Chemotherapy: First Results From Penelope-B

A SUMMARY Double-Blind, Placebo-Controlled Randomized Phase III Trial Evaluating First-Line Ipatasertib Combined With Paclitaxel for PIK3CA/AKT1/PTEN-Altered Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer: Primary Results From IPATunity130 Cohort AThe IPATunity130 phase 3 trial enrolled 255 patients with chemotherapy-naive, locally advanced unresectable or metastatic triple-negative breast cancer that was PIK3CA/AKT1-altered and/or PTEN-altered (Abstract GS3-04). Patients were randomly assigned 2:1 to receive either ipatasertib at 400 mg or placebo (days 1-21), both combined with paclitaxel at 80 mg/m(2) (days 1, 8, and 15) in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal. Approximately 51% had received neoadjuvant chemotherapy, 59% had visceral disease, 51% had PIK3CA/AKT1-activating mutations, and 49% had PTEN alterations only. After a median follow-up of 8.3 months, 33% of patients remained on treatment. The mean paclitaxel dose intensity was similar between the groups. There was no significant difference in PFS between treatment arms overall or in any prespecified subgroups. OS results are immature, but preliminary findings revealed no significant difference between the treatment arms. Similar proportions of patients in the study arms experienced grade 3/4 AEs, fatal AEs, or AEs leading to discontinuation of any treatment. AEs leading to dose reduction of any treatment were more common with ipatasertib.