ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
Phase I Study of an AKT Inhibitor (MK-2206) Combined with Lapatinib in Adult Solid Tumors Followed by Dose Expansion in Advanced HER2+ Breast Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
- Pre-surgical trial of the AKT inhibitor MK-2206 in patients with operable invasive breast cancer: a New York Cancer Consortium trial.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2018Trial
- GATRSyn: Advancing Anticancer Drug Synergy Prediction Through Graph Attention Networks and Transformer-based Feature Re-embedding.Interdisciplinary sciences, computational life sciences · 2026Article
- Phosphoproteomic and Acetylomic Characterization of Colorectal Cancer Cells Treated with Kinase Inhibitors.ACS pharmacology & translational science · 2025Article
- Genomic Predictive Biomarkers in Breast Cancer: TheInternational journal of molecular sciences · 2025Review
- The Landscape of Potential Targeted Treatments and Chemotherapy Efficacy Biomarkers for TNBC.Breast cancer (Dove Medical Press) · 2025Review
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- MMFSyn: A Multimodal Deep Learning Model for Predicting Anticancer Synergistic Drug Combination Effect.Biomolecules · 2024Article
- Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.Molecular cancer · 2023Review
- Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.Cancers · 2023Article
- PI3K-AKT-Targeting Breast Cancer Treatments: Natural Products and Synthetic Compounds.Biomolecules · 2023Review
- PRODeepSyn: predicting anticancer synergistic drug combinations by embedding cell lines with protein-protein interaction network.Briefings in bioinformatics · 2022Article
- Identification of BIK as an unfavorable prognostic marker and novel therapeutic target in microsatellite stable colorectal cancer harboring KRAS mutations.American journal of cancer research · 2022Article
- The HSP-RTK-Akt axis mediates acquired resistance to Ganetespib in HER2-positive breast cancer.Cell death & disease · 2021Article
- Clinical Development of AKT Inhibitors and Associated Predictive Biomarkers to Guide Patient Treatment in Cancer Medicine.Pharmacogenomics and personalized medicine · 2021Review
- AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?Frontiers in pharmacology · 2021Review
- Article
- Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cellsOncotarget · 2020Article
- Ubiquitin-specific peptidase 17 promotes cisplatin resistance via PI3K/AKT activation in non-small cell lung cancer.Oncology letters · 2020Article
- Combination Therapy and Nanoparticulate Systems: Smart Approaches for the Effective Treatment of Breast Cancer.Pharmaceutics · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
purposePreclinical data support combining AKT inhibitors with HER2-targeted therapies to overcome resistance to treatment. This phase I study combined the investigational AKT inhibitor, MK-2206, with lapatinib to determine the MTD. EXPERIMENTAL
designThe dose escalation cohort enrolled adults with advanced solid tumors, who received MK-2206 dosed 30 to 60 mg every other day and lapatinib 1,000 to 1,500 mg daily continuously, escalated using a 3+3 design. Cycles were 28 days except cycle 1 (35 days, including an initial 8 days of MK-2206 alone to evaluate pharmacokinetic interactions). The dose expansion cohort enrolled adults with advanced HER2(+) breast cancer.
resultsTwenty-three participants enrolled in the dose escalation cohort. Dose-limiting toxicities were hyponatremia, fatigue, rash, hypocalcemia, and mucositis. Common toxicities included diarrhea, nausea, and rash. The MTD was reached at MK-2206 45 mg orally every other day and lapatinib 1,500 mg orally daily. Two participants maintained stable disease for >4 months, including a colorectal cancer participant with substantial carcinoembryonic antigen decrease. Of 5 participants in the dose expansion cohort, 2 maintained stable disease for >6 months, including one with prior progression on single-agent lapatinib. Plasma MK-2206 concentrations decreased after addition of lapatinib, but in vitro studies indicate lapatinib increases the intracellular levels of MK-2206.
conclusionsMK-2206 combined with lapatinib can be tolerated with both drugs above biologically active single-agent doses. Overlapping toxicities result in significant diarrhea and rash, which can be managed medically. Antitumor activity was promising and supports evaluation of AKT inhibitors combined with HER2-targeted therapies. Clin Cancer Res; 22(11); 2659-67. ©2016 AACR.
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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.