Trial reportBreast cancer research : BCR2019
Phase II trial of AKT inhibitor MK-2206 in patients with advanced breast cancer who have tumors with PIK3CA or AKT mutations, and/or PTEN loss/PTEN mutation.
Trial report in Breast cancer research : BCR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01277757 (Phase II Trial of AKT Inhibitor MK2206 in Patients With Advanced Breast Cancer Who Have Tumors With a PIK3CA Mutation, or an AKT Mutation, and/or PTEN Loss/PTEN Mutation), which is not on this map. Cited by 133 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Trial of AKT Inhibitor MK2206 in Patients With Advanced Breast Cancer Who Have Tumors With a PIK3CA Mutation, or an AKT Mutation, and/or PTEN Loss/PTEN Mutation
Who cites it
133 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Treatment-related adverse events in patients with advanced breast cancer receiving adjuvant AKT inhibitors: a meta-analysis of randomized controlled trials.European journal of clinical pharmacology · 2024Pooled it
- Which Is the Most Appropriate PI3K Inhibitor for Breast Cancer Patients with or without PIK3CA Status Mutant? A Systematic Review and Network Meta-Analysis.BioMed research international · 2020Pooled it
- Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer.Breast cancer research : BCR · 2020Trial
- Targeting the PI3K/Akt Signaling Pathway: A Promising Therapeutic Strategy to Reduce Cancer Mortality and Overcome Chemoresistance.Health science reports · 2026Article
- Emerging Strategies Targeting the PI3K/AKT/mTOR Pathway in HR+/HER2- Advanced Breast Cancer.Drugs · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Current and future therapies for triple-negative breast cancer.Journal of hematology & oncology · 2026Review
- A Computational Investigation of Four Sesquiterpene [4+2] Trimers, Inubritantrimers A-D, and Their Synthetic Intermediates Isolated fromMolecules (Basel, Switzerland) · 2026Article
- Remarkable response of metaplastic breast cancer to a novel targeted AKT inhibitor TAS-117 in a Cowden syndrome patient: a case report.BJC reports · 2026Article
- mTORC2 inhibition reduces tumor burden via STAT1 activation and enhanced response to anti-PD-L1 therapy.Cell death & disease · 2025Article
- Article
- Enhancing Chemotherapeutic Efficacy in Lung Cancer Cells Through Synergistic Targeting of the PI3K/AKT Pathway with Small Molecule Inhibitors.International journal of molecular sciences · 2025Article
- Genomic characterization of tumor mutational burden-high breast carcinomas.NPJ precision oncology · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Genomic Predictive Biomarkers in Breast Cancer: TheInternational journal of molecular sciences · 2025Review
- Review
- Mutational analysis and protein expression of PI3K/AKT pathway in four mucinous cystadenocarcinoma of the breast.Diagnostic pathology · 2025Article
- Treatment strategies targeting the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway against triple-negative breast cancer.World journal of clinical oncology · 2025Review
- Interpretable prediction of drug synergy for breast cancer by random forest with features from Boolean modeling of signaling pathways.Scientific reports · 2025Article
- An exposure-safety analysis to support the dosage of the novel AKT inhibitor capivasertib.Cancer chemotherapy and pharmacology · 2025Article
73 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
26 authors at 7 institutions in 2 countries.
Funding
Abstract
backgroundThe PI3K/AKT pathway is activated through PIK3CA or AKT1 mutations and PTEN loss in breast cancer. We conducted a phase II trial with an allosteric AKT inhibitor MK-2206 in patients with advanced breast cancer who had tumors with PIK3CA/AKT1 mutations and/or PTEN loss/mutation.
methodsThe primary endpoint was objective response rate (ORR). Secondary endpoints were 6-month progression-free survival (6 m PFS), predictive and pharmacodynamic markers, safety, and tolerability. Patients had pre-treatment and on-treatment biopsies as well as collection of peripheral blood mononuclear cells (PBMC) and platelet-rich plasma (PRP). Next-generation sequencing, immunohistochemistry, and reverse phase protein arrays (RPPA) were performed.
resultsTwenty-seven patients received MK-2206. Eighteen patients were enrolled into the PIK3CA/AKT1 mutation arm (cohort A): 13 had PIK3CA mutations, four had AKT1 mutations, and one had a PIK3CA mutation as well as PTEN loss. ORR and 6 m PFS were both 5.6% (1/18), with one patient with HR+ breast cancer and a PIK3CA E542K mutation experiencing a partial response (on treatment for 36 weeks). Nine patients were enrolled on the PTEN loss/mutation arm (cohort B). ORR was 0% and 6 m PFS was 11% (1/9), observed in a patient with triple-negative breast cancer and PTEN loss. The study was stopped early due to futility. The most common adverse events were fatigue (48%) and rash (44%). On pre-treatment biopsy, PIK3CA and AKT1 mutation status was concordant with archival tissue testing. However, two patients with PTEN loss based on archival testing had PTEN expression on the pre-treatment biopsy. MK-2206 treatment was associated with a significant decline in pAKT S473 and pAKT T308 and PI3K activation score in PBMC and PRPs, but not in tumor biopsies. By IHC, there was no significant decrease in median pAKT S473 or Ki-67 staining, but a drop was observed in both responders.
conclusionsMK-2206 monotherapy had limited clinical activity in advanced breast cancer patients selected for PIK3CA/AKT1 or PTEN mutations or PTEN loss. This may, in part, be due to inadequate target inhibition at tolerable doses in heavily pre-treated patients with pathway activation, as well as tumor heterogeneity and evolution in markers such as PTEN conferring challenges in patient selection.
trial registrationClinicalTrials.gov, NCT01277757 . Registered 13 January 2011.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.