Research table: PI3 kinase inhibitors and AKT inhibitors for metastatic breast cancer treatment

This summary table contains detailed information about research studies. Summary tables are a useful way to look at the science behind many breast cancer guidelines and recommendations. However, to get the most out of the tables, it’s important to understand some key concepts. Learn how to read a research table.

Introduction: The PI3 kinase, AKT and PTEN enzymes are on the same cellular pathway. They are important in cell growth and division.

Some breast cancers have a PIK3CA, AKT1 or PTEN gene mutation. These are mutations in the genes of the breast cancer cells, not the genes of the person.

A PIK3CA, AKT1 or PTEN tumor gene mutation can affect PI3 kinase and/or AKT activity and cause the cancer to grow. PI3 kinase inhibitors and AKT inhibitors are drugs designed to block this action.

PI3 kinase inhibitors

Alpelisib (Piqray) and inavolisib (Itovebi) are PI3 kinase inhibitor drugs used to treat some hormone receptor-positive, HER2-negative metastatic breast cancers that have a PIK3CA gene mutation.

Alpelisib in combination with the hormone therapy drug fulvestrant can give people more time before the cancer worsens compared to treatment with fulvestrant alone.

Inavolisib in combination with the CDK4/6 inhibitor palbociclib and the hormone therapy drug fulvestrant can give people more time before the cancer worsens compared to treatment with palbociclib and fulvestrant alone.

Learn more about alpelisib and inavolisib, including their side effects.

AKT inhibitors

Capivasertib (Truqap) is an AKT inhibitor drug used to treat some hormone receptor-positive, HER2-negative metastatic breast cancers that have a PIK3CA, AKT1 or PTEN gene mutation, and have been treated with at least one hormone therapy in the metastatic setting in the past.

Capivasertib in combination with fulvestrant can give people more time before the cancer worsens compared to treatment with fulvestrant alone.

Learn more about capivasertib, including its side effects.

Study selection criteria: Randomized clinical trials with 300 or more participants with hormone receptor-positive, HER2-negative metastatic breast cancer.

Study	Study Population (number of participants)	Drug(s) Used	Objective Response Rate—Percent who Responded to Treatment (95% CI)	Progression-free survival (survival with no breast cancer spread) (95% CI)
Randomized clinical trials – PI3 kinase inhibitors
SOLAR-1 [1]	341*	Alpelisib plus fulvestrant	27%†	Progression-free survival at one year: 46%†
		Fulvestrant alone	13%†	Progression-free survival at one year: 33%†
INAVO120 [2]	325*	Inavolisib plus palbociclib and fulvestrant	58%†	Progression-free survival at one year: 56%†
		Palbociclib and fulvestrant alone	25%†	Progression-free survival at one year: 33%†
Study	Study Population (number of participants)	Drug(s) Used	Objective Response Rate—Percent who Responded to Treatment (95% CI)	Overall Survival (95% CI)
Randomized clinical trials – AKT inhibitors
CAPItello-291 Study Group [3]	708‡	Capivasertib plus fulvestrant	23%†	Overall survival at 18 months: 74%†
		Fulvestrant alone	12%†	Overall survival at 18 months: 65%†

* All participants had breast cancer with a PIK3CA tumor gene mutation

† Statistically significant difference between the 2 treatment groups

‡ All participants had breast cancer with a PIK3CA, AKT1 or PTEN tumor gene mutation

References

1. André F, Ciruelos E, Rubovszky G, et al. for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 380(20):1929-1940, 2019.
2. Turner NC, Im SA, Saura C, et al. Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer. N Engl J Med. 391(17):1584-1596, 2024.
3. Turner NC, Oliveira M, Howell SJ, et al. for the CAPItello-291 Study Group. Capivasertib in hormone receptor-positive advanced breast cancer. N Engl J Med. 388(22):2058-2070, 2023.

Updated 11/05/24