Research table: Drugs that target PI3 kinase, AKT, PTEN and mTOR 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 and mTOR enzymes are on the same cellular pathway. They are important in cell growth and division. PI3 kinase inhibitors, AKT inhibitors, mTOR inhibitors and pan-PI3 kinase-mTOR inhibitors are drugs that target different parts of this pathway to block cancer growth.

Some of these drugs are used to treat breast cancers that have a PIK3CA, AKT1 or PTEN tumor gene mutation. These mutations are in the genes of the breast cancer cells, not the genes of the person.

Learn more about these drugs, including their side effects.

PI3 kinase inhibitors

Alpelisib (Piqray) and inavolisib (Itovebi) are PI3 kinase inhibitor drugs. They are 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 fulvestrant can give people more time before the cancer worsens and may improve overall survival compared to treatment with palbociclib and fulvestrant alone.

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.

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

mTOR inhibitors

Everolimus (Afinitor) is an mTOR inhibitor used to treat some hormone receptor-positive, HER2-negative metastatic breast cancers.

The combination of everolimus and hormone therapy give people more time before the cancer worsens compared to hormone therapy alone.

pan-PI3K-mTOR inhibitors

Gedatolisib (Revtorpyk) is a pan-PI3K-mTOR inhibitor used to treat some hormone receptor-positive, HER2-negative metastatic breast cancers that do not have a PIK3CA tumor gene mutation.

Gedatolisib in combination with the hormone therapy drug fulvestrant (with or without a CDK4/6 inhibitor drug) can give people more time before the cancer worsens compared to fulvestrant alone.

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	62%†	Progression-free survival at one year: 58%†,‡ Progression-free survival at 2 years: 42%†,‡
		Palbociclib and fulvestrant alone	28%†	Progression-free survival at one year: 31%†,‡ Progression-free survival at 2 years: 17%†,‡
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%†
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) better with everolimus?
Randomized clinical trials – mTOR inhibitors
BOLERO-2 [4-5]	724	Everolimus plus exemestane	13%†	Yes†
		Exemestane alone	2%†
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) better with gedatosilib?
Randomized clinical trials – pan-PI3K-mTOR inhibitors
VIKTORIA-1 [6]	392	Gedatosilib plus fulvestrant	28%||	Yes†
		Gedatosilib plus fulvestrant and palbociclib	32%||	Yes†
		Fulvestrant alone	1%||

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

† Statistically significant difference between the 2 treatment groups.

‡ Overall survival at one year was better in the inavolisib plus palbociclib and fulvestrant group (87%) compared to the palbociclib and fulvestrant group (77%). Overall survival at 2 years was also better in the inavolisib plus palbociclib and fulvestrant group (66%) compared to the palbociclib and fulvestrant group (56%).

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

|| Statistically significant difference between the treatment groups with gedatosilib and the treatment group without gedatosilib.

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. Jhaveri KL, Im SA, Saura C, et al. Overall survival with inavolisib in PIK3CA-mutated advanced breast cancer. N Engl J Med. 393(2):151-161, 2025.
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.
4. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone receptor-positive advanced breast cancer. N Engl J Med. 366(6):520-9, 2012.
5. Yardley DA, Noguchi S, Pritchard KI, et al. Everolimus plus exemestane in postmenopausal patients with HR+ breast cancer: BOLERO-2 final progression-free survival analysis. Adv Ther. 30(10):870–884, 2013.
6. Hurvitz SA, Layman RM, Curigliano G, et al for the VIKTORIA-1 Study Group. VIKTORIA-1 trial of gedatolisib plus fulvestrant with or without palbociclib in hormone receptor-positive/HER2-/PIK3CA wild-type advanced breast cancer. J Clin Oncol. 44(12):1108-1119, 2026.

Updated 09/02/26