ArticleJournal of the National Cancer Institute2015
SU2C phase Ib study of paclitaxel and MK-2206 in advanced solid tumors and metastatic breast cancer.
Open access · bronzeAbstract readClinical Trial, Phase I
In one paragraph
Article in Journal of the National Cancer Institute, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- MK-2206 and Standard Neoadjuvant Chemotherapy Improves Response in Patients With Human Epidermal Growth Factor Receptor 2-Positive and/or Hormone Receptor-Negative Breast Cancers in the I-SPY 2 Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- 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.Breast cancer research : BCR · 2019Trial
- 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
- Momentum contrast-enhanced multimodal representation learning for drug synergy prediction.Bioinformatics (Oxford, England) · 2026Article
- 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
- Beyond Anti-PD-1/PD-L1: Improving Immune Checkpoint Inhibitor Responses in Triple-Negative Breast Cancer.Cancers · 2024Review
- PI3K-AKT-Targeting Breast Cancer Treatments: Natural Products and Synthetic Compounds.Biomolecules · 2023Review
- CIP2A as a Key Regulator for AKT Phosphorylation Has Partial Impact Determining Clinical Outcome in Breast Cancer.Journal of clinical medicine · 2022Article
- Combined Application of Pan-AKT Inhibitor MK-2206 and BCL-2 Antagonist Venetoclax in B-Cell Precursor Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2021Article
- Platelet Proteomes, Pathways, and Phenotypes as Informants of Vascular Wellness and Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- AKT Inhibitors: New Weapons in the Fight Against Breast Cancer?Frontiers in pharmacology · 2021Review
- Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cellsOncotarget · 2020Article
- Targeting AKT for cancer therapy.Expert opinion on investigational drugs · 2019Review
- Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells.Cancers · 2019Article
- Genome atlas analysis based profiling of Akt pathway genes in the early and advanced human prostate cancer.Oncoscience · 2019Article
- Communication between mitochondria and other organelles: a brand-new perspective on mitochondria in cancer.Cell & bioscience · 2019Review
- MK-2206 window of opportunity study in breast cancer.Annals of translational medicine · 2018Article
- E-cadherin loss induces targetable autocrine activation of growth factor signalling in lobular breast cancer.Scientific reports · 2018Article
- Targeting the PI3K pathway in cancer: are we making headway?Nature reviews. Clinical oncology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 4 institutions in 1 country.
Ana M Gonzalez-AnguloDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Ian KropDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Argun AkcakanatDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Huiqin ChenDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Shuying LiuDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Yisheng LiDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Kirk S CulottaDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Emily TarcoDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Sarina Piha-PaulDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Stacy Moulder-ThompsonDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Vivianne Velez-BravoDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Aysegul A SahinDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Laurence A DoyleDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Kim-Anh DoDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Eric P WinerDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Gordon B MillsDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Razelle KurzrockDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD).
Funda Meric-BernstamDepartments of Breast Medical Oncology (AMGA, SL, SMT), Systems Biology (AMGA, GBM), Biostatistics (HC, YL, K-AD), Experimental Therapeutics (KSC), Investigational Cancer Therapeutics (AA, ET, SPP, VV-B, FMB), Pathology (AAS) and Surgical Oncology (FMB), The University of Texas MD Anderson Cancer Center, Houston, TX; Division of Hematology-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (IK, EPW); Division of Hematology-Oncology, University of California, San Diego, CA (RK); Cancer Therapy Evaluation Program, NIH/National Cancer Institute, Rockville, MD (LAD). fmeric@mdanderson.org.
Harvard University · USUniversity of California, San Diego · USDana-Farber Cancer Institute · USCancer Clinic · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MUNIVERSITY OF TEXAS MD ANDERSON SPORE IN OVARIAN CANCERP50CA083639 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BAST, ROBERT C · 1999 to 2015
$33.0MPhase I Studies of Targeted Anti-Cancer TherapiesU01CA062461 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI YAO, JAMES C · 1994 to 2013
$7.2MThe PI3K/PTEN/AKT Signal Transduction Cascade in Breast CancerK23CA121994 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI GONZALEZ-ANGULO, ANA M. · 2006 to 2010
$680kNCI NIH HHS 1K23CA121994NCI NIH HHS P50 CA083639NCI NIH HHS U01 CA062461-18
Abstract
backgroundThere is preclinical synergism between taxanes and MK-2206. We aim to determine the maximum tolerated dose, safety, and activity of combining MK-2206 and paclitaxel in metastatic cancer.
methodsPatients received weekly doses of paclitaxel at 80mg/m2 on day 1, followed by MK-2206 orally on day 2 escalated at 90mg, 135mg, and 200mg. Treatment continued until progression, excessive toxicity, or patient request. Blood and tissue were collected for pharmacokinetic and pharmacodynamics markers. A cycle consisted of three weeks of therapy. Dose-limiting toxicity (DLT) was defined as unacceptable toxicity during the first cycle. All statistical tests were two-sided.
resultsTwenty-two patients were treated, nine in dose escalation and 13 in dose expansion. Median age was 55 years. Median number of cycles was four. Dose escalation was completed with no DLT. CTCAE Grade 3 or higher adverse events were fatigue (n = 2), rash (n = 2), hyperglycemia (n = 1), and neutropenia (n = 7). Four patients in the expansion phase required MK-2206 dose reduction. Phase II recommended dose was established as paclitaxel 80mg/m2 weekly on day 1, and MK-2206 135mg weekly on day 2. Paclitaxel systemic exposure was similar in the presence or absence of MK-2206. Plasma MK-2206 concentrations were similar to data from previous phase I monotherapy. There was a statistically significant decrease in expression of pAKT S473 (P = .01) and pAKT T308 (P = .002) after therapy. PI3K/AKT/mTOR downregulation in tumor tissues and circulating markers did not correlate with tumor response or clinical benefit. There were five objective responses, and nine patients had stable disease.
conclusionMK-2206 was well tolerated with paclitaxel. Preliminary antitumor activity was documented.
Indexed as
AdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDrug Administration ScheduleDrug EruptionsFatigueFemaleHeterocyclic Compounds, 3-RingHumansHyperglycemiaMaleMaximum Tolerated DoseMiddle AgedNeoplasmsBiomarkers, TumorHeterocyclic Compounds, 3-RingMK 2206Paclitaxel
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