Hope S. Rugo, MD, FASCO, discusses background and key findings from the phase 3 CAPItello-291 trial in breast cancer.
Hope S. Rugo, MD, FASCO, director of Breast Oncology and Clinical Trials Education and professor of medicine in the Division of Hematology and Oncology at the University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center, discusses the methods, design, and key findings from the phase 3 CAPItello-291 trial (NCT04305496).
In the randomized, double-blind study, patients with aromatase inhibitor (AI)-resistant hormone receptor-positive/HER2-negative advanced breast cancer were enrolled and given the combination of capivasertib plus fulvestrant or placebo plus .
According to Rugo, there was a significant improvement in progression-free survival among those treated with the combination of capivasertib plus fulvestrant.
0:08 | The CAPItello-291 trial was a phase 3, randomized, double-blind study that evaluated an AKT inhibitor called capivasertib in combination with fulvestrant compared with placebo/fulvestrant in patients who have hormone receptor-positive metastatic breast cancer that had pretreatment with an aromatase inhibitor followed by disease progression. The trial allowed chemotherapy as well as 1 line of chemotherapy, and didn't require CDK4/6 inhibitors. But 69% of patients had CDK4/6 inhibitors, and about 20% of patients had 1 line of prior chemotherapy.
0:50 | The trial evaluated the addition of this AKT inhibitor, and the trial was designed to look in the intent-to-treat, the overall population, and then to look at a co primary end point of progression-free survival in the patients whose tumors had alterations in the ATT pathway to find this having activating mutations in PIK3CA, or AKT, or PTEN deletion. That has been looked at in tumor tissue in the study. The trial showed in the patient population, that about 40% of patients had an alteration in the pathway. There was also a subgroup of patients 16%, relatively low for a trial like this, who didn't have results from tumor tissue. So either the tumor tissue wasn't preserved enough, or there wasn't enough tumor tissue sent. But they basically had no information about mutation status.
1:39 | The results of the trial showed that progression-free survival was significantly improved in patients who received capivasertib with their fulvestrant, whether it was the intent-to-treat population or the sub population of patients, and about 40%, who had an alteration in the AKT pathway, which is how they've termed it now as opposed to the PI3 kinase pathway. That was interesting. We were interested then in the population who are wild-type for the alterations in this pathway. In that group of patients, which included the unknown group, there was still a benefit, the hazard ratio went up a little bit, but the confidence intervals didn't cross 1. There is still that question about what is going on with the 16% of unknown patients. Hopefully that data will be obtained by looking at a circulating tumor DNA, and that is dependent on having a good assay looking at PTEN in circulating tumor DNA where you can look at AKT mutations, but PTEN is still being developed and validated, so we'll see.