Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2020
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.
Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 1 of them a synthesis that pooled it.
What it found
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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
74 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Precision Oncology Clinical Trials: A Systematic Review of Phase II Clinical Trials with Biomarker-Driven, Adaptive Design.Cancer research and treatment · 2024Pooled it
- Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2025Trial
- Neoadjuvant Trebananib plus Paclitaxel-based Chemotherapy for Stage II/III Breast Cancer in the Adaptively Randomized I-SPY2 Trial-Efficacy and Biomarker Discovery.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.Annals of oncology : official journal of the European Society for Medical Oncology · 2021Trial
- Trial
- Design, simulate, refine: simulation-guided clinical trials for accelerated drug development.Nature reviews. Drug discovery · 2026Review
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Image Quality Assessment of Diffusion-Weighted Imaging (DWI) and Its Impact on Apparent Diffusion Coefficient (ADC) as a Quantitative Imaging Biomarker for Predicting Response to Neoadjuvant Chemotherapy in High-Risk Early Breast Cancer.Tomography (Ann Arbor, Mich.) · 2026Article
- Unveiling Candidate Markers for Drug Resistance or Synthetic Lethality in Cervical Cancer: Integrative Analysis of Genetic and Pharmacoprofiling.Cancer reports (Hoboken, N.J.) · 2026Article
- Tumor heterogeneity index from DCE-MRI for AKT-inhibition responder identification and reveals hot immune microenvironment for patients with breast cancer: a multi-omics analysis of I-SPY2 trial.Breast cancer research : BCR · 2026Article
- Mining Chemotherapy Resistance Related Genes in Breast Cancer to Construct a New Prognosis Prediction Model-Based on GEO Database and Real-World Study.Human mutation · 2026Article
- Transcriptional modulation of the PI3K/AKT/mTOR signaling pathway mediated by HPV16Exploration of targeted anti-tumor therapy · 2026Article
- COPS5 inhibition synergizes with the antitumor effect of trastuzumab by PTEN upregulation in HER2-amplified gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2025Article
- Breast Cancer Treatments: Drugs Targeting the PI3K/AKT/mTOR Pathway, TNBC Therapy and Future Directions: A Review.Life (Basel, Switzerland) · 2025Review
- Novel mutations of SRPX facilitate the stemness and malignant progression of glioma.British journal of cancer · 2025Article
- Single-cell and spatial transcriptomics reveal mechanisms of radioresistance and immune escape in recurrent nasopharyngeal carcinoma.Nature genetics · 2025Article
- Carrier-free nano-integrated strategy of phototherapy and chemotherapy for synergetic AKT targeted therapy to inhibit cancer metastasis and recurrence.Journal of nanobiotechnology · 2025Article
- Immune Subtyping Identifies Patients With Hormone Receptor-Positive Early-Stage Breast Cancer Who Respond to Neoadjuvant Immunotherapy (IO): Results From Five IO Arms of the I-SPY2 Trial.JCO precision oncology · 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
- NEK2 promotes the progression of osteosarcoma through the AKT/p-AKT pathway and interacts with FoxM1.Medical oncology (Northwood, London, England) · 2025Article
14 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
50 authors at 20 institutions in 1 country.
Funding
Abstract
purposeThe phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin is a key pathway of survival and therapeutic resistance in breast cancer. We evaluated the pan-Akt inhibitor MK-2206 in combination with standard therapy in patients with high-risk early-stage breast cancer. PATIENTS AND
methodsI-SPY 2 is a multicenter, phase II, open-label, adaptively randomized neoadjuvant platform trial that screens experimental therapies and efficiently identifies potential predictive biomarker signatures. Patients are categorized by human epidermal growth factor receptor 2 (HER2), hormone receptor (HR), and MammaPrint statuses in a 2 × 2 × 2 layout. Patients within each of these 8 biomarker subtypes are adaptively randomly assigned to one of several experimental therapies, including MK-2206, or control. Therapies are evaluated for 10 biomarker signatures, each of which is a combination of these subtypes. The primary end point is pathologic complete response (pCR). A therapy graduates with one or more of these signatures if and when it has an 85% Bayesian predictive probability of success in a hypothetical phase III trial, adjusting for biomarker covariates. Patients in the current report received standard taxane- and anthracycline-based neoadjuvant therapy without (control) or with oral MK-2206 135 mg/week.
resultsMK-2206 graduated with 94 patients and 57 concurrently randomly assigned controls in 3 graduation signatures: HR-negative/HER2-positive, HR-negative, and HER2-positive. Respective Bayesian mean covariate-adjusted pCR rates and percentage probability that MK-2206 is superior to control were 0.48:0.29 (97%), 0.62:0.36 (99%), and 0.46:0.26 (94%). In exploratory analyses, MK-2206 evinced a numerical improvement in event-free survival in its graduating signatures. The most significant grade 3-4 toxicity was rash (14% maculopapular, 8.6% acneiform).
conclusionThe Akt inhibitor MK-2206 combined with standard neoadjuvant therapy resulted in higher estimated pCR rates in HR-negative and HER2-positive breast cancer. Although MK-2206 is not being further developed at this time, this class of agents remains of clinical interest.
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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.