News > New breast cancer drug targets AKT pathway

New breast cancer drug targets AKT pathway

Capivasertib on track for possible FDA approval in metastatic hormone receptor-positive disease



Endocrine or hormonal therapies are a mainstay of treatment for metastatic hormone receptor-positive, HER2-negative breast cancer. There are many drug options yet, over time, cancers stop responding to them—called treatment resistance—leaving fewer options to halt cancer growth. An important line of research looks for therapies to treat breast cancers that no longer respond to endocrine therapy.

Earlier studies identified the AKT pathway as potentially playing a role in resistance to hormonal therapy. The AKT pathway can become altered in cancers with PIK3CA, AKT1, or PTEN genetic mutations. These mutations are found using tumor biomarker (or genomic) testing. Doctors hypothesize that a drug that targets this pathway may be effective in treating breast cancers with hormone resistance. The AKT pathway is a new target for cancer treatment.


CAPItello-291 was a double-blind, randomized trial that compared the effectiveness of the new AKT-inhibitor capivasertib plus fulvestrant (Faslodex) to a placebo (non-active medicine) plus fulvestrant in people with metastatic, HR+, HER2- breast cancer. Fulvestrant alone is the standard therapy given after a cancer progresses upon initial treatment. This phase III trial was open to pre- and postmenopausal women and men. The participants were mostly white and Asian, and included very few Black people.

The research team compared the benefit of the drug in both people with AKT-altered pathways and those without. They used next-generation sequencing (tumor biomarker, or genomic, testing) to identify PIK3CA, AKT1, or PTEN to determine AKT pathway alteration.

Overall, adding the AKT-inhibitor capivasertib was beneficial to people in the study. This was true, regardless of AKT alteration status. On average, participants who received capivasertib went twice as long without cancer growing as those taking fulvestrant only (7.2 months versus 3.6 months). The results were slightly better for people whose cancers had an AKT alteration (7.3 months versus 3.1 months).

The analysis also considered the presence of liver metastases, past use of a CDK 4/6 inhibitor, and geographic region. No differences were noted in the first two groups. The investigator did not comment on differences by region, so it was likely not a factor. An earlier phase II study conducted before this trial did not include people who had taken CDK 4/6 inhibitors, so the effectiveness in this group is new and important information, since today most people take CDK 4/6 inhibitors upon diagnosis with HR+, HER2- metastatic breast cancer.

Diarrhea was the main side effect for those taking capivasertib. About 72% of participants reported diarrhea, which was described as mild for most and improved over time. About 2% of people stopped taking the drug because of diarrhea. Nearly one-third of participants in the study group had nausea, also mostly mild. Rash and fatigue were the next most frequent side effects, with less than 25% reporting each.

What this means for you

These clinical trial results will likely result in an FDA approval of capivasertib for metastatic HR+, HER2- breast cancer that no longer responds to endocrine therapy. Capivasertib was more effective against cancers with altered AKT pathways, yet the difference was slim, so it may not be required to take this drug; that decision will be up to the FDA.

If you are interested in capivasertib, talk with your doctor about this study and whether this medicine might be an option for you. Let them know about the study results for people with and without liver metastases, and for those who have or have not taken CDK 4/6 inhibitors.


Related resources


Stay connected

Sign up to receive emotional support, medical insight, personal stories, and more, delivered to your inbox weekly.