TY - JOUR
T1 - Exploratory Analysis of PTEN Deficiency by Immunohistochemistry from the Phase III CAPItello-291 Trial
AU - Jhaveri, Komal
AU - Rugo, Hope S.
AU - Cortés, Javier
AU - Oliveira, Mafalda
AU - Howell, Sacha J.
AU - Dalenc, Florence
AU - Gomez, Henry L.
AU - Hu, Xichun
AU - Krivorotko, Petr
AU - Loibl, Sibylle
AU - Okera, Meena
AU - Park, Yeon Hee
AU - Sohn, Joohyuk
AU - Toi, Masakazu
AU - Tokunaga, Eriko
AU - Zhukova, Lyudmila
AU - Nardone, Agostina
AU - Wadsworth, Ian
AU - D’cruz, Celina
AU - Wantenaar, Tanya
AU - Das, Dimple
AU - de Bruin, Elza C.
AU - Turner, Nicholas C.
N1 - Publisher Copyright:
© 2026 The Authors; Published by the American Association for Cancer Research.
PY - 2026/8/15
Y1 - 2026/8/15
N2 - Purpose: The phosphoinositide 3-kinase (PI3K)/AKT serine/ threonine kinase (AKT) pathway is frequently activated in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, with loss of phosphatase and tensin homolog (PTEN) activity contributing to this activation. Capivasertib is a potent pan-AKT inhibitor, approved in combination with fulvestrant for the treatment of HR-positive/HER2-negative locally advanced/metastatic breast cancer with one or more PIK3CA/AKT1/PTEN tumor alterations. Next-generation sequencing (NGS) is commonly used to identify patients with PIK3CA/AKT1/PTEN tumor alterations. However, the utility of immunohistochemistry (IHC) to identify patients with PTEN-deficient tumors has not been explored in this context. Experimental Design: This exploratory analysis was based on tumor samples collected from patients in the global phase III CAPItello-291 study. Results: PTEN IHC results were obtained for 367 tumor samples, with 70 (19.1%) identified as PTEN deficient by IHC. A total of 346 (94.3%) samples with a PTEN IHC test result also had NGS test results available for PIK3CA/AKT1/PTEN alteration status. When comparing PTEN deficiency by IHC with PTEN alteration status by NGS, the overall, positive, and negative percent agreements were 87.0% (301/346), 71.9% (23/32), and 88.5% (278/314), respectively. Exploratory analysis in patients with PTEN-deficient tumors by IHC (n = 70) showed improved progression-free survival in the capivasertib plus fulvestrant versus placebo plus fulvestrant treatment arm (median 9.3 vs. 3.7 months; hazard ratio: 0.52, 95% confidence interval, 0.28– 0.90). Conclusions: These results suggest potential utility for IHC in determining tumor PTEN status in breast cancer and raise the possibility of IHC identifying additional patients who could benefit from treatment with capivasertib and fulvestrant.
AB - Purpose: The phosphoinositide 3-kinase (PI3K)/AKT serine/ threonine kinase (AKT) pathway is frequently activated in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, with loss of phosphatase and tensin homolog (PTEN) activity contributing to this activation. Capivasertib is a potent pan-AKT inhibitor, approved in combination with fulvestrant for the treatment of HR-positive/HER2-negative locally advanced/metastatic breast cancer with one or more PIK3CA/AKT1/PTEN tumor alterations. Next-generation sequencing (NGS) is commonly used to identify patients with PIK3CA/AKT1/PTEN tumor alterations. However, the utility of immunohistochemistry (IHC) to identify patients with PTEN-deficient tumors has not been explored in this context. Experimental Design: This exploratory analysis was based on tumor samples collected from patients in the global phase III CAPItello-291 study. Results: PTEN IHC results were obtained for 367 tumor samples, with 70 (19.1%) identified as PTEN deficient by IHC. A total of 346 (94.3%) samples with a PTEN IHC test result also had NGS test results available for PIK3CA/AKT1/PTEN alteration status. When comparing PTEN deficiency by IHC with PTEN alteration status by NGS, the overall, positive, and negative percent agreements were 87.0% (301/346), 71.9% (23/32), and 88.5% (278/314), respectively. Exploratory analysis in patients with PTEN-deficient tumors by IHC (n = 70) showed improved progression-free survival in the capivasertib plus fulvestrant versus placebo plus fulvestrant treatment arm (median 9.3 vs. 3.7 months; hazard ratio: 0.52, 95% confidence interval, 0.28– 0.90). Conclusions: These results suggest potential utility for IHC in determining tumor PTEN status in breast cancer and raise the possibility of IHC identifying additional patients who could benefit from treatment with capivasertib and fulvestrant.
UR - https://www.scopus.com/pages/publications/105047397906
U2 - 10.1158/1078-0432.CCR-25-2965
DO - 10.1158/1078-0432.CCR-25-2965
M3 - Artículo
C2 - 42154572
AN - SCOPUS:105047397906
SN - 1078-0432
VL - 32
SP - 3599
EP - 3607
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 16
ER -
ODS 3: Salud y bienestar