Breast cancer, PIK3CA-mutated

Section editor
	H. Deepika Fernandes, MD, FACP Virginia G. Piper Cancer Care Network Comprehensive Breast Center of Arizona Scottsdale, AZ LinkedIn

3 regimens on this page 3 variants on this page

Note: this page has regimens which are specific to breast cancer that is PIK3CA-mutated. Please see the main breast cancer page for other chemotherapy regimens.

Advanced or metastatic disease, all lines of therapy

Alpelisib & Fulvestrant

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
André et al. 2019 (SOLAR-1) ESMO-MCBS (2)	2015-2017	Phase 3 (E-RT-esc)	Fulvestrant	Superior PFS1 Median PFS: 11 vs 5.7 mo (HR 0.65, 95% CI 0.50-0.85)

¹Reported efficacy is for the cohort of patients with PIK3CA-mutated cancer.
Note: patients enrolled in this trial had HR-positive breast cancer.

Targeted therapy

• Alpelisib (Piqray) 300 mg PO once per day

Endocrine therapy

• Fulvestrant (Faslodex) as follows:
  • Cycle 1: 500 mg IM once per day on days 1 & 15
  • Cycle 2 onwards: 500 mg IM once on day 1

28-day cycles

References

1. SOLAR-1: André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. link to original article contains dosing details in manuscript PubMed Clinical Trial Registry
   1. Update: André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Pápai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. Epub 2020 Nov 25. link to original article PubMed
   2. PRO analysis: Ciruelos EM, Rugo HS, Mayer IA, Levy C, Forget F, Delgado Mingorance JI, Safra T, Masuda N, Park YH, Juric D, Conte P, Campone M, Loibl S, Iwata H, Zhou X, Park J, Ridolfi A, Lorenzo I, André F. Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1. J Clin Oncol. 2021 Jun 20;39(18):2005-2015. Epub 2021 Mar 29. link to original article link to PMC article PubMed

Fulvestrant monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
André et al. 2019 (SOLAR-1)	2015-2017	Phase 3 (C)	Alpelisib & Fulvestrant	Inferior PFS
Dent et al. 2020 (SANDPIPER)	2015-2017	Phase 3 (C)	Taselisib & Fulvestrant	Inferior PFS

Note: patients enrolled in these trials had HR-positive breast cancer.

Endocrine therapy

• Fulvestrant (Faslodex) as follows:
  • Cycle 1: 500 mg IM once per day on days 1 & 15
  • Cycle 2 onwards: 500 mg IM once on day 1

28-day cycles

References

1. SOLAR-1: André F, Ciruelos E, Rubovszky G, Campone M, Loibl S, Rugo HS, Iwata H, Conte P, Mayer IA, Kaufman B, Yamashita T, Lu YS, Inoue K, Takahashi M, Pápai Z, Longin AS, Mills D, Wilke C, Hirawat S, Juric D; SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor-positive advanced breast cancer. N Engl J Med. 2019 May 16;380(20):1929-1940. link to original article contains dosing details in manuscript PubMed Clinical Trial Registry
   1. Update: André F, Ciruelos EM, Juric D, Loibl S, Campone M, Mayer IA, Rubovszky G, Yamashita T, Kaufman B, Lu YS, Inoue K, Pápai Z, Takahashi M, Ghaznawi F, Mills D, Kaper M, Miller M, Conte PF, Iwata H, Rugo HS. Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1. Ann Oncol. 2021 Feb;32(2):208-217. Epub 2020 Nov 25. link to original article PubMed
   2. PRO analysis: Ciruelos EM, Rugo HS, Mayer IA, Levy C, Forget F, Delgado Mingorance JI, Safra T, Masuda N, Park YH, Juric D, Conte P, Campone M, Loibl S, Iwata H, Zhou X, Park J, Ridolfi A, Lorenzo I, André F. Patient-Reported Outcomes in Patients With PIK3CA-Mutated Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer From SOLAR-1. J Clin Oncol. 2021 Jun 20;39(18):2005-2015. Epub 2021 Mar 29. link to original article link to PMC article PubMed
2. SANDPIPER: Dent S, Cortés J, Im YH, Diéras V, Harbeck N, Krop IE, Wilson TR, Cui N, Schimmoller F, Hsu JY, He J, De Laurentiis M, Sousa S, Drullinsky P, Jacot W. Phase III randomized study of taselisib or placebo with fulvestrant in estrogen receptor-positive, PIK3CA-mutant, HER2-negative, advanced breast cancer: the SANDPIPER trial. Ann Oncol. 2021 Feb;32(2):197-207. Epub 2020 Nov 10. link to original article link to PMC article PubMed Clinical Trial Registry

Paclitaxel monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Turner et al. 2021 (IPATunity130)	2018-2019	Phase 3 (C)	Ipatasertib & Paclitaxel	Did not meet primary endpoint of PFS

Biomarker eligibility criteria

• HR+ HER2-negative PIK3CA/AKT1/PTEN-altered

Chemotherapy

• Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

1. IPATunity130: Turner N, Dent RA, O'Shaughnessy J, Kim SB, Isakoff SJ, Barrios C, Saji S, Bondarenko I, Nowecki Z, Lian Q, Reilly SJ, Hinton H, Wongchenko MJ, Kovic B, Mani A, Oliveira M. Ipatasertib plus paclitaxel for PIK3CA/AKT1/PTEN-altered hormone receptor-positive HER2-negative advanced breast cancer: primary results from cohort B of the IPATunity130 randomized phase 3 trial. Breast Cancer Res Treat. 2022 Feb;191(3):565-576. Epub 2021 Dec 3. link to original article contains dosing details in abstract link to PMC article PubMed Clinical Trial Registry