Exploratory Analysis of PTEN Deficiency by Immunohistochemistry from the Phase III CAPItello-291 Trial
Year: 2026
Type: article
Abstract: 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.
Source: Clinical Cancer Research
Authors: Komal Jhaveri, Hope S. Rugo, Javier Cortés, Mafalda Oliveira, Sacha J. Howell, Florence Dalenc, Henry L. Gomez, Xichun Hu, Petr Krivorotko, Sibylle Loibl, Meena Okera, Yeon Hee Park, Joohyuk Sohn, Masakazu Toi, Eriko Tokunaga, Lyudmila Zhukova, Agostina Nardone, Ian Wadsworth, Celina D’Cruz, Tanya Wantenaar, Dimple Das, Elza C. de Bruin, Nicholas C. Turner
Institutions: Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, MedSIR (Spain), Universidad Europea de Madrid, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, The Christie NHS Foundation Trust, Institut universitaire du cancer de Toulouse Oncopole, Universidad Ricardo Palma, Instituto Nacional de Enfermedades Neoplásicas, Fudan University, Fudan University Shanghai Cancer Center, Institute of Oncology NN Petrov, Samsung Medical Center, Sungkyunkwan University, Yonsei University, Yonsei Cancer Hospital, Kyoto University Hospital, National Hospital Organization Kyushu Cancer Center, Moscow Clinical Scientific Center, AstraZeneca (Spain), AstraZeneca (United Kingdom), AstraZeneca (United States), Institute of Cancer Research, Royal Marsden Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: AstraZeneca UK, National Cancer Institute
Award: Cancer Center Support Grant
OpenAlex ID: W7161699299