Trial reportBMC cancer2019
Relationship between tumor biomarkers and efficacy in MARIANNE, a phase III study of trastuzumab emtansine ± pertuzumab versus trastuzumab plus taxane in HER2-positive advanced breast cancer.
Trial report in BMC cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT01120184 (A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo), which is not on this map. Cited by 41 papers, 1 of them a synthesis 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.
A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Line Treatment in HER2 Positive Progressive or Recurrent Locally Advanced or Metastatic Breast Cancer
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Risk of Ophthalmotoxicity Associated with Antibody-Drug Conjugates: A Systematic Review and Meta-analysis.Clinical drug investigation · 2025Pooled it
- Phase II study (KAMELEON) of single-agent T-DM1 in patients with HER2-positive advanced urothelial bladder cancer or pancreatic cancer/cholangiocarcinoma.Cancer medicine · 2023Trial
- Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE).Breast cancer research : BCR · 2023Trial
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- Prognostic Role of Inflammatory Indices and Real-World Outcomes in HER2-Positive Metastatic Breast Cancer Treated with Trastuzumab Emtansine.Diagnostics (Basel, Switzerland) · 2026Article
- Final Efficacy and Safety Results of Pyrotinib Combined With Trastuzumab and Chemotherapy in Pre-Treated Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer.Cancer medicine · 2026Article
- Predictive Biomarkers of Antibody-Drug Conjugate Efficacy for Solid Tumors: Current Challenges and the Potential Role of Quantitative Proteomics.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Spatial single-cell multi-omics characterization of the tumor microenvironment heterogeneity by HER-2 expression status in gastric cancer.Molecular cancer · 2026Article
- Addition of Ipatasertib to Dual Anti-HER2 Maintenance Therapy in HER2-Positive Metastatic Breast Tumors with PIK3CA Mutations: The Phase Ib SOLTI-1507 IPATHER Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Real-World Analysis of the Efficacy and Adverse Events of T-DM1 in Chinese Patients With HER2-Positive Breast Cancer.Breast cancer (Dove Medical Press) · 2025Article
- Clinico-pathological predictors of radiologic complete response to first-line anti-HER2 therapy in metastatic breast cancer.NPJ breast cancer · 2024Article
- Evolving Management of Breast Cancer in the Era of Predictive Biomarkers and Precision Medicine.Journal of personalized medicine · 2024Review
- Management of patients with advanced-stage HER2-positive breast cancer: current evidence and future perspectives.Nature reviews. Clinical oncology · 2024Review
- The Development of a Chest-Pain Protocol for Women Presenting to the Emergency Department.CJC open · 2024Review
- Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial).NPJ breast cancer · 2024Article
- A nationwide real-world study for evaluation of effectiveness and safety of T-DM1 in patients with HER2-positive metastatic breast cancer in Korea (KCSG BR19-15).Therapeutic advances in medical oncology · 2024Article
- Predicting Response to Antibody Drug Conjugates: A Focus on Antigens' Targetability.The oncologist · 2023Article
- ConcomitantJournal of breast cancer · 2023Article
- Development, efficacy and side effects of antibody‑drug conjugates for cancer therapy (Review).Molecular and clinical oncology · 2023Review
- Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 11 institutions in 9 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe phase III EMILIA and TH3RESA trials demonstrated clinical benefits of trastuzumab emtansine (T-DM1) therapy in patients with previously treated HER2-positive metastatic breast cancer (MBC). Data from these and other trials showed that T-DM1-associated survival benefits were observed across biomarker subgroups tested in these trials. Prespecified, exploratory analyses of the phase III MARIANNE study examined the effects of HER2-related biomarkers on PFS in patients administered T-DM1 in the first-line MBC setting.
methodsIn MARIANNE, patients with previously untreated HER2-positive MBC were randomized (1:1:1) to trastuzumab plus taxane, T-DM1 plus placebo, or T-DM1 plus pertuzumab. Biomarker subgroups included HER2 and HER3 mRNA expression levels (≤median vs. >median), HER2 staining intensity (IHC 3+ vs. 2+ vs. 0/1+), PIK3CA status (mutated vs. non-mutated), PTEN H-score (≤median vs. >median), and PTEN protein expression level (0 vs. 1+ vs. 2+ vs. 3+ vs. 4+). PFS was analyzed descriptively for each subgroup using Kaplan-Meier methodology. Additional exploratory post-hoc analyses evaluated the effects of HER2 heterogeneity. Multivariate analyses were also performed.
resultsMedian PFS was numerically longer for patients with HER2 mRNA levels >median versus ≤median across treatment arms. In general, there were no predictive biomarkers of benefit for either T-DM1 treatment arm; most hazard ratios were close to 1 with wide confidence intervals that included the value 1. Focal HER2 expression (IHC 3+ or IHC 2+) was present in 3.8% of patients and was associated with numerically shorter PFS in the T-DM1-containing treatment arms versus trastuzumab plus taxane. Compared with non-mutated PIK3CA, mutated PIK3CA was associated with numerically shorter median PFS across treatment groups. Post-hoc multivariate analysis showed HER2 mRNA expression and mutated PIK3CA were prognostic for PFS (P ≤ 0.001 for both biomarkers).
conclusionsIn MARIANNE, biomarkers related to the HER2 pathway did not have predictive value for PFS when comparing T-DM1 (with or without pertuzumab) with trastuzumab plus taxane. However, HER2 mRNA level and PIK3CA mutation status showed prognostic value. Evaluation of other potential biomarkers, including immune markers, is ongoing.
trial registrationRegistration number: NCT01120184 . Date of registration: April 28, 2010 (registered prospectively).
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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.