Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Recurrence

Breast Diseases

Skin Diseases

Disease Attributes

PAM50 results is as one of the references for the physicians and the participants to choose adjuvant treatments.

PAM50

Yen-Shen Lu, MD, PhD

This project aims to establish the cancer genome atlas and the platform of recurrence risk prediction specific for East Asian breast cancer patients. The study was planned to collect blood sample, fresh tumor tissue, and paraffin embedded tumor tissue from 2000 patients. Aims to identify unique genetic alterations in Asian tumors, to identify the susceptible genes for breast carcinogenesis in East Asia, and to establish the new platform for accurate prediction of recurrence. The investigator will explore the association of patient outcomes with the genetic alterations from the cancer atlas of East Asian breast tumors.

East Asian Breast Cancer Genome Atlas and Recurrence Risk Prediction

The Cancer Genome Atlas and Recurrence Risk Prediction of East Asian Breast Cancer: a Multicenter Collaborative Study

To establish the cancer genome atlas and identify the susceptible genes for breast carcinogenesis in East Asia

To establish the new platform for accurate prediction of recurrence

National Taiwan University Hospital

Antineoplastic Agents

All Drugs and Chemicals

Bone Density Conservation Agents

Amino Acids

Trastuzumab

Paclitaxel

Tamoxifen

Letrozole

Albumin-Bound Paclitaxel

Mitogens

Lapatinib

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Tyrosine

For a total of 18 weeks, HR-negative patients will be given dual blockade consisting of daily lapatinib at 1000 mg and trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks.

For a total of 18 weeks, HR-positive patients will be given letrozole (2.5 mg daily) or tamoxifen (20 mg daily) with concurrent dual blockade consisting of daily lapatinib at 1000 mg and trastuzumab at a loading dose of 8 mg/kg, followed by 6 mg/kg every 3 weeks.

Letrozole or tamoxifen will be prescribed according to patient's menopausal status

Endocrine Therapy

Only administrated if tumor progression is observed by US on week 6

Antonio Llombart, MD, PhD

Aleix Prat, MD, PhD

Javier Cortés, MD, PhD

Non-randomized, open label, multicentric translational research study in women with untreated invasive breast carcinoma eligible for primary surgery (Stage I-IIIA).

The aim of PAMELA is to test the hypothesis that PAM50 HER2-enriched (HER2-E) subtype better predicts response to neoadjuvant dual anti-HER2 blockade, with or without endocrine therapy, compared to traditional clinical HER2 classification. Furthermore, we posit that characterization of gene expression patterns may identify profiles of those who may be safely spared chemotherapy.

PAMELA is a non-randomized, open label, multicentric translational research study of neoadjuvant dual HER2 blockade therapy without chemotherapy. Although efficacy and safety will be investigated, the primary goal is to identify profiles predictive of clinical benefit from targeted therapy. Eligible patients must be women with untreated primary HER2-overexpressing and/or amplified breast tumors of more than 1 cm in diameter amenable to definitive surgery (stage I-IIIA).

The PAMELA study is designed to test the hypothesis that the PAM50 HER2-E subtype is able to predict clinical response to neoadjuvant dual HER2 blockade with lapatinib and trastuzumab, with or without endocrine therapy, assessed by pathological complete response in the breast (pCRB) rate at the time of surgery, compared to traditional clinical HER2 classification. Furthermore, we posit that characterization of gene expression patterns may identify profiles of those who may be safely spared chemotherapy.

Patients will first undergo screening, tumor measurement, and mandatory collection of core tumor biopsies for central determination of HER2 and HR status. These biopsies will be used to determine gene expression patterns once the patient is included in the study. Patients will be treated with dual HER2 blockade consisting of lapatinib and trastuzumab for a total of 18 weeks. Patients who are HR-positive will also be given endocrine therapy, letrozole or tamoxifen depending on their menopausal status, for the same 18 weeks. If tumor progression is observed by ultrasound (US) at week 6, tumors will be identified as resistant, and paclitaxel will be added to dual HER2 blockade, maintaining trastuzumab at the same original dose and reducing lapatinib dose for safety reasons. In those patients with HR-positive disease, endocrine therapy will be withdrawn in order to avoid its adverse interactions with chemotherapy.

Two weeks after the first administration of study medication, all patients will undergo mandatory repeat tumor tissue acquisition that will be used for secondary endpoint assessment.

Post treatment tissue acquisition will be obtained at the time of surgery from the specimen excised.

US of the breast and axillary lymph nodes will be performed at baseline, Day 14, week 6, and prior to surgery, and will be correlated with pCR. If tumor progression is observed on week 6, the US will be repeated on week 10 to discard the progression continues despite the addition of paclitaxel at neoadjuvant regimen.

Mammography is required at baseline and prior to surgery, but will not be used for the objective response assessment.

Treatment will be given until definitive surgery, clinical signs of disease progression after paclitaxel addition, unacceptable toxicity or withdrawal of patient consent.

Breast surgery will be carried out 1 to 3 weeks after completion of dual HER2 blockade with or without endocrine therapy, and 2 to 3 weeks after completion of paclitaxel plus dual HER2 blockade, should it had been initiated for progressive disease.

Following surgical excision, adjuvant treatment will be as per investigator´s choice and local standards of care outside the scope of this protocol.

End of study is 30 days (±14 days) after surgery with a safety follow-up visit.

PAM50 HER2-enriched Phenotype as a Predictor of Response to Dual HER2 Blockade in HER2-positive Early Breast Cancer

PAMELA: PAM50 HER2-enriched Phenotype as a Predictor of Early Response to Neoadjuvant Lapatinib Plus Trastuzumab in Stage I to IIIA HER2-positive Breast Cancer

Comparison between the PAM50 HER2-E versus non HER2-E cases to achieve pCRB from dual HER2 blockade with lapatinib and trastuzumab at the time of surgery

Comparison between the PAM50 HER2-E versus non HER2-E cases to achieve pCRBL from dual HER2 blockade with lapatinib and trastuzumab at the time of surgery

Correlation between PAM50 HER2-E cases and RCB status (0-I versus II-III) after dual HER2 blockade with lapatinib and trastuzumab at the time of surgery

Comparison of the changes in the percentage of Ki67-positive cells in Luminal versus non-Luminal subtypes after 14 days of dual HER2 blockade plus endocrine therapy

Compare significant changes in gene expression from baseline to Day 14 in the entire study population and separately, in the HR-negative and HR-positive patients

In all patients and in those with HR-positive and HR-negative disease

Correlation between the PAM50 ROR and pCR and/or RCB after dual HER2 blockade with lapatinib and trastuzumab at the time of surgery

Identification of gene expression changes that correlate with pCRB or RCB after dual HER2 blockade treatment

Frequency of adverse events (AE)(assessed by CTCAE v.4.03), including the following parameters:

* All reported AEs and serious AEs
* Neutropenia Grade 3/4
* Febrile neutropenia Grade 3/4
* Neuropathy Grade 3/4
* Myalgia/arthralgia
* Cardiotoxicity (Grade 3/4 or NYHA Class III or IV)
* Frequency of dose reductions and dose delays due to treatment toxicity

Novartis

SOLTI Breast Cancer Research Group

Pembrolizumab

Immune Checkpoint Inhibitors

200 mg Pembrolizumab IV Q3W plus 80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.

80 mg/m2 paclitaxel IV on Days 1,8, and 15 of each 28 day cycle.

Peter Schmid, MD PhD FRCP

PELICAN is a randomised phase II trial that aims to evaluate the efficacy and safety of paclitaxel plus pembrolizumab relative to paclitaxel alone, in patients with locally advanced or metastatic ER-positive, HER2-negative, Luminal B breast cancer who have received no prior chemotherapy for advanced or metastatic disease.

Patients will be randomised (2:1) to one of the two treatment arms:

* Pembrolizumab plus Paclitaxel
* Paclitaxel

Paclitaxel Plus Pembrolizumab vs. Paclitaxel Weekly in ER+ Luminal B Metastatic Breast Cancer

A Phase II, Randomized Study of Paclitaxel Weekly Plus Pembrolizumab Versus Paclitaxel Weekly in ER-positive, Luminal B Metastatic Breast Cancer

Progression-free survival, defined as the time from the date of randomisation to the date of first documented tumour progression (using RECIST 1.1) or death from any cause, whichever occurs first.

Overall Survival is defined as the time from date of randomisation to the date of death due to any cause in all patients.

Objective Response Rate is defined as the proportion of the patients in the analysis population who have a CR or PR (using RECIST 1.1).

Incidence, nature and severity of adverse events with severity determined according to CTCAE v4.03

Merck Sharp & Dohme LLC

European Institute of Oncology

Queen Mary University of London

Pertuzumab

Trial treatment is defined as neoadjuvant therapy only. The Investigational Medicinal Products (IMPs) are pembrolizumab, trastuzumab biosimilar and pertuzumab.

* Trastuzumab Biosimilar (Trazimera®) - Investigational Medicinal Product

  * Loading dose: 8 mg/kg bodyweight at initial administration infusion over 90 min; monitor patient for at least 6 h afterwards.
  * Maintenance dose: 6 mg/kg bodyweight, over 30-90 min; monitor patient for 2 h afterwards.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.
* Pertuzumab (Perjeta®) - Investigational Medicinal Product

  * Loading dose: 840 mg, initial administration.
  * Maintenance dose: 420 mg.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.
* Pembrolizumab (Keytruda®) - Investigational Medicinal Product

  * Dose: 200 mg.
  * Route: Intravenous infusion.
  * Schedule: Every 3 weeks during the neoadjuvant phase.

Intravenous infusion; 200 mg; every 3 weeks

Intravenous infusion; 8 mg/kg loading dose, thereafter 6 mg/kg; every 3 weeks

Trastuzumab Biosimilar ABP 980

Intravenous infusion; 840 mg/kg loading dose, thereafter 420 mg/kg; every 3 weeks

s.kuemmel@kem-med.com Kuemmel, Professor

Keyriched-1 is a multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar ABP 980 and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

HER2-positive breast cancer is best defined by multiparameter gene expression profiling rather than analysis of the overexpression/amplification status of only HER2. As this subgroup is often correlated with a high expression of TILs and PD/PD-L1, immunogenic therapy strategies seem very promising. The pCR highly correlates with the overall outcome of patients with HER2-positive breast cancer \[7\]. Therefore, the pCR rate after neoadjuvant treatment has been adopted as a surrogate endpoint and, more recently, as a basis for accelerated drug approval \[38\].

Due to the high number of patients achieving a pCR after standard treatment of anti-HER2 therapy combined with chemotherapy, de-escalated strategies seem promising and designing a chemotherapy-free trial regimen is therefore modern, justifiable and of high scientific value. Therefore, we designed a prospective phase II, single arm, hypothesis-generating trial investigating the rate of pCR in patients with HER2-enriched breast cancer receiving four cycles of dual anti-HER2 blockade in combination with the checkpoint inhibitor pembrolizumab. Further translational research will be added to gain further insight into the tumor response or resistance to this treatment approach. The addition of standard chemotherapy after this study treatment will be at the discretion of the investigator. In case of a non-pCR after study treatment, continuing treatment with chemotherapy and antihormonal therapy in case of HR positive disease is highly recommended.

A multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.

A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)

A Prospective, Multicenter, Open Label, Neoadjuvant Phase II Single Arm Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype

pCR defined as no invasive tumor in breast and lymph nodes (ypT0/is, ypN0) at surgery after study treatment

AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.

Descriptive analysis by number of observations and their percentage.

NanoString Technologies, Inc.

West German Study Group

Menopause

Vinorelbine

* Oral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks
* Letrozole: 2.5mg daily, for 3 weeks

Oral Vinorelbine: 50 mg (30 mg + 20 mg) three times a week, for 3 weeks

Metronomic Schedule of Vinorelbine administered orally in a schedule monday-wednesday-friday, tuesday-thursday-saturday, etc

Oral Vinorelbine

Letrozole will be administered orally at 2.5 mg QD for 3 weeks.

VENTANA is a "window-of-opportunity" trial that will explore whether, similar to CDK4/6 inhibitors, Oral Metronomic Vinorelbine in combination with Letrozole induces a superior anti-proliferative effect than Letrozole alone.

VENTANA is a phase 0 multicenter, window of opportunity, three-arm, randomized clinical trial of oral metronomic vinorelbine (VNB) and letrozole versus either treatment alone in postmenopausal women with newly diagnosed untreated HR+ and HER2-negative, stage I-III operable breast cancer. Other eligibility criteria include primary tumor size 1 cm (cT1-3) and N0-1, ECOG PS 0-1 and evaluable diagnostic tumor sample.

Primary objective is to test if Oral Metronomic Vinorelbine and Letrozole induce a superior anti-proliferative effect than either drug alone in patients with early breast cancer defined as Luminal by PAM50/HER2-negative. This will be evaluated by measuring the expression of 11 proliferative genes contained in the PAM50/Prosigna® array (BIRC5, CCNB1, CDC20, CDCA1, CEP55, KNTC2, MKI67, PTTG1, RRM2, TYMS and UBE2C), as surrogate biomarker of its anticancer activity. By evaluating other breast cancer-related gene signatures (560 genes), the antiangiogenic and immunogenic potential of treatment arms will be compared and other genes regulated in a treatment-specific manner identified. These analyses will be performed in different PAM50-defined subtypes (Luminal, LuminalA or LuminalB). Clinical efficacy and safety of treatments will also be evaluated.

Patients will first undergo screening and mandatory collection of core tumor biopsies for study analysis. Patients are randomized (1:1:1) to receive Letrozole 2.5mg daily, oral Vinorelbine 50mg 3 days a week or Letrozole 2.5mg daily and oral Vinorelbine 50mg 3 times a week. After 3 weeks of treatment, patients will undergo surgery, and both pre-treatment and post-treatment surgery samples will be analyzed. Alternatively, if surgery will be delayed, a tumor core biopsy will be collected. Anyway, post-treatment sample should be collected within 5 days after end of treatment in order to observe the biological response.

Axillar and mammary surgery will be done according to local standards; however, sentinel lymph node biopsy previous to surgery is not permitted. Following surgical excision, adjuvant treatment will be as per investigator´s choice and local standards of care outside the scope of this protocol. End of study is 28 days (±3 days) after last study drug dose with a safety follow-up visit.

Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole in HR+/HER2-negative Early Breast Cancer Patients (VENTANA)

Randomized, Open-label, Three-arm, Parallel, Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole Versus Letrozole or Vinorelbine Alone in Post-menopausal Women With Hormone Receptor-positive HER2-negative Early Breast Cancer

* Outcome measure determined by following formula: Mean suppression of proliferation signature score = 100 - \[geometric mean (post treatment proliferation score/pre-treatment proliferation score · 100)\].
* Comparison of the Oral Metronomic Vinorelbine (VNB)+Letrozole arms versus VNB or Letrozole monotherapy arms in patients defined as Luminal by PAM50.

* Outcome measure determined by following formula: Mean suppression of proliferation signature score = 100 - \[geometric mean (post treatment proliferation score/pre-treatment proliferation score · 100)\].
* Comparison of the 3 treatment arms in the entire study population (evaluable patients defined as Luminal by IHC) and separately, in patients defined as either Luminal A or Luminal B by PAM50

Comparison of the 3 treatment arms in the entire PAM50-defined Luminal population (LuminalA+LuminalB) and separately, in the LuminalA or LuminalB subtypes.

* Expression data of breast cancer genes will be log base 2 transformed and normalized using 5 house-keeping genes
* Analysis will be performed in the entire PAM50-defined Luminal population (LuminalA+LuminalB) and separately, in the LuminalA or LuminalB subtypes.
* Aim of this outcome measure is to identify those genes with a significant difference between the VNB+Letrozole arms compared to the VNB or Letrozole monotherapy arms.

* Incidence and severity of Adverse Events (assessed by CTCAE v.4.03)
* Incidence of treatment interruptions due to toxicity

Pierre Fabre Laboratories

Herbal and Botanical

Exemestane

Anastrozole

Orange

In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.

In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

Lapatinib is available as 250-mg orange tablets. Subjects randomized to the Lapatinib plus Trastuzumab arm received 1000 mg per day of Lapatinib, so wre instructed to take 4 x 250 mg tablets per day. Lapatinib was to be taken either 1 hour (or more) before a meal or 1 hour (or more) after a meal

Trastuzumab is a sterile, white to pale yellow, preservative-free lyophilized powder for IV administration. Trastuzumab was administered on Day 1 of the start of Lapatinib or in conjunction with the first cycle of chemotherapy, as an 8 mg/kg loading dose. Subsequently, Trastuzumab was administered q3weekly as a 6 mg/kg maintenance dose. At the discretion of the investigator, weekly Trastuzumab could be given in either of the three treatment arms (loading dose 4mg/kg followed by weekly administration of 2mg/kg).

Subjects who were hormone receptor-positive were required to receive an aromatase inhibitor as combination treatment; however the choice of the aromatase inhibitor selected for each patient was determined by the patients' investigator. The AIs the Investigator could choose from were anastrozole, exemestane, and letrozole and dosing was per product information.

Aromatase Inhibitors (AIs)

Novartis Pharmaceuticals

This was a multicenter, open-label, Phase II study in subjects with Human epidermal growth factor receptor (HER2)-positive metastatic breast cancer who received at least 2 prior lines of anti-HER2-targeted therapies of which at least one included a Trastuzumab-containing regimen. This study was a post-approval commitment with regulatory authorities. It was designed to evaluate whether treatment with Dual blockade promoted changes to biomarkers associated with immunomodulation.

This study was designed to address the post-authorization measures as agreed with the Committee for Medicinal Products for Human Use (CHMP). Recruitment of subjects into this study was challenging, and following agreement with the European Medicines Agency (EMA) enrollment into this study was halted after the enrollment of 42 of the 225 planned subjects.

The primary endpoint of the study evaluated changes in expression of biomarkers associated with immunomodulation between a pre-treatment biopsy and the disease progression biopsy. Secondary efficacy endpoints included overall response rate, clinical benefit rate and progression-free survival (PFS), as well as safety/tolerability. All subjects received study treatment until disease progression, death, unacceptable toxicity, or subject withdrawal. In case of disease progression during the treatment period, the subject was followed-up for 30 days for safety evaluation. In case of study treatment discontinuation for any reasons other than disease progression, the subject was followed-up for safety and efficacy assessments until disease progression, new anticancer therapy, death, withdrawal of consent or end of study, whichever came first.

This study supported a better understanding of the rapidly accumulating evidence for the importance of the immune microenvironment in HER2-positive breast cancer and the observed immunomodulation in the neoadjuvant setting could be confirmed in the advanced setting and supported the putative mechanism of action of HER2 dual blockade and its potential function on the tumor microenvironment. No formal comparisons between treatment arms were undertaken.

Participants were randomized to Arms A and B but randomized to Arm C.

This was a two-cohort, three-arm, open-label Phase II study to evaluate the changes in the expression of biomarkers between pre-treatment and progression biopsy in subjects with Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Subjects were allocated to 1 of 2 cohorts depending on the molecular subtype of their biopsy.

Cohort 1 HER2 -enriched included HER2-positive subjects with a HER2-Enriched molecular subtype, and were randomized in a 1:1 ratio to receive either trastuzumab in combination with lapatinib (Arm A) or trastuzumab in combination with chemotherapy (Arm B).

Cohort 2 non-HER2-enriched, included HER2-positive subjects with luminal A, luminal B, and basal-like molecular subtypes and were to receive trastuzumab in combination with lapatinib (Arm C). Subjects with hormone receptor (ER and/or PgR)-positive MBC in this arm were required to be treated with an AI of the Investigator's choice.

Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer

An Open-Label, Phase II, Study to Evaluate Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer Receiving Treatment With Trastuzumab in Combination With Lapatinib or Chemotherapy (EGF117165)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Evaluate changes in biomarkers associated with immunomodulation between pre-treatment biopsy and disease progression biopsy within each arm. Biomarker analysis was performed using an mRNA gene expression panel derived from Nanostring platform in a total of 20 subjects who received the study treatment as per the study design and with baseline tumor biopsies available.

For the selected biomarkers associated with immunomodulation, the median fold changes of gene expression level and 95% confidence interval are presented. The fold change was calculated as the ratio of the expression level of a biomarker at disease progression over the baseline.

PFS was defined as the time from the date of randomization (for Arm A and B) / treatment start date (for Arm C) to the date of the first documented disease progression or death due to any cause, whichever was earlier. If a subject had not progressed or died at the analysis cutoff date, PFS was censored at the time of the last adequate tumor assessment. PFS was summarized using Kaplan-Meier estimates.

Overall response rate was defined as the percentage of subjects achieving either a confirmed complete response (CR) or partial response (PR) and was calculated from the Investigator's assessment of response per RECIST 1.1 criteria. . The confirmed CR or PR was derived using the following rules: confirmed CR - at least two determinations of CR at least 4 weeks apart before disease progression; confirmed PR - at least two determinations of PR or better at least 4 weeks apart before progression.

CBR is defined as percentage of subjects with a complete response (CR), partial response (PR), or maintaining stable disease (SD) for at least 24 weeks while on study according to the investigator assessment of response per RECIST 1.1 criteria. CR and PR are confirmed responses derived using the following rules: Confirmed CR - at least 2 determinations of CR at least 4 weeks apart before disease progression. Confirmed PR - at least 2 determinations of PR or better at least 4 weeks apart before progression.

Describe if changes of biomarker expression at disease progression from baseline correlate with PFS.

Adverse Event: Any sign or symptom that occurs during the study treatment plus the 30 days post treatment.

Lapatinib 1000mg + Trastuzumab in HER2 Enriched In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

LAP+TRAS±AI (HER2-Enriched) - Arm A

Trastuzumab in HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of HER2 Enriched, Trastuzumab (loading dose of 8 mg/kg followed by the maintenance dose of 6 mg/kg IV q3weekly) along with chemotherapy of the investigator's choice or Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly along with chemotherapy of the investigators choice. Subjects randomized to this arm and hormone receptor positive received an aromatase inhibitor at the discretion of the investigator.

TRAS+CHEM±AI (HER2-Enriched) • ArmB

Lapatinib 1000mg + Trastuzumab in Non- HER2 Enriched: In subjects with HER2-overexpressing MBC with a molecular subtype of Non- HER2 Enriched (luminal A, luminal B or Basal type), Lapatinib 1000mg once daily orally along with Trastuzumab (loading dose of 8 milligram/ kilogram (mg/kg) followed by the maintenance dose of 6 mg/kg Intravenous (IV) Every 3 weeks (q3weekly)) or Lapatinib 1000 milligram (mg) once daily orally along with Weekly Trastuzumab (loading dose of 4 mg/kg) followed by maintenance dose of 2 mg/kg IV weekly. For subjects who were hormone receptor positive, an aromatase inhibitor of the investigator's choice was required.

Non-HER2-Enriched - Arm C

TRAS+CHEM±AI (HER2-Enriched) - Arm B

Non-HER2- Enriched - Arm C

Total

< 65 years

>= 65 years

Age, Customized

Sex: Female, Male

Caucasian

African American

Asian

Native Hawaiian or Pacific Islander

Race/Ethnicity, Customized

Full Analysis Set (FAS): Consisted of all subjects who were randomized to study Arm A or Arm B or assigned to study Arm C, irrespective of whether they actually received study treatment.

Study Director

Membrane spanning 4-domains A1

POU class 2 associating factor 1

CD19+

Interleukin 6

G antigen 1

ubiquitin specific peptidase 9, Y-linked

Thy-1 cell surface antigen

Chemerin chemokine-like receptor 1

Major histocompatibility complex, class II, DR beta 4

Collectin subfamily member 12

Complement C3b/C4b receptor 1 (Knops blood group)

CD33 molecule

B-cell linker

Interleukin 12A

CD163+

C-C motif chemokine ligand 8

Chemokine (C-C motif) receptor 1

POU class 2 homeobox 2

Cyclin dependent kinase inhibitor 1A

CD27 molecule

Lymphocyte antigen 86

TNF superfamily member 8

CD34+

Integrin subunit alpha 6

C-type lectin domain containing 7A

CD180 molecule

Integrin subunit alpha M

Toll like receptor 6

Autophagy related 10

C-C motif chemokine ligand 3 like 1

Bone marrow stromal cell antigen 1

CD22+

CD37 molecule

NEG_A

Sperm auto antigenic protein 17

CD200 molecule

TNF receptor associated factor 3

Interferon alpha and beta receptor subunit 1

TNF receptor associated factor 6

Evaluable Set: Included all subjects in Arm A who received the study treatment and had both baseline and progression tumor biopsies available, with evaluable data for at least 1 biomarker.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
East Asian Breast Cancer Genome Atlas and Recurrence Risk Prediction	NCT04344496	Breast Cancer	PAM50	20 Years -	National Taiwan University Hospital
East Asian Breast Cancer Genome Atlas and Recurrence Risk Prediction	NCT04344496	Breast Cancer	PAM50	20 Years -	National Taiwan University Hospital
PAM50 HER2-enriched Phenotype as a Predictor of Response to Dual HER2 Blockade in HER2-positive Early Breast Cancer	NCT01973660	Breast Cancer	Lapatinib Trastuzumab Endocrine Thera... Paclitaxel	18 Years -	SOLTI Breast Cancer Research Group
Paclitaxel Plus Pembrolizumab vs. Paclitaxel Weekly in ER+ Luminal B Metastatic Breast Cancer	NCT03841747	Breast Cancer	Pembrolizumab Paclitaxel	18 Years -	Queen Mary University of London
A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)	NCT03988036	Breast Cancer	Pembrolizumab Trastuzumab Bio... Pertuzumab	18 Years -	West German Study Group
Phase 0 Study of Metronomic Oral Vinorelbine and Letrozole in HR+/HER2-negative Early Breast Cancer Patients (VENTANA)	NCT02802748	Breast Cancer	Oral Vinorelbin... Letrozole	18 Years -	SOLTI Breast Cancer Research Group
Evaluation of Biomarkers Associated With Response to Subsequent Therapies in Subjects With HER2-Positive Metastatic Breast Cancer	NCT02213042	Neoplasms, Brea...	Lapatinib Trastuzumab Aromatase Inhib...	18 Years -	Novartis
A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)	NCT03988036	Breast Cancer	Pembrolizumab Trastuzumab Bio... Pertuzumab	18 Years -	West German Study Group
Pharmacogenomic Study of Neoadjuvant Eribulin for HER2 Non-overexpressing Breast Cancer	NCT01669252	Breast Cancer	Eribulin	18 Years -	SOLTI Breast Cancer Research Group
Trastuzumab Deruxtecan Versus Standard Neoadjuvant Treatment for HER2-positive Breast Cancer	NCT05900206	Breast Cancer	Trastuzumab der... Docetaxel Paclitaxel Carboplatin Trastuzumab Pertuzumab Ribociclib Letrozole Epirubicin Cyclophosphamid...	18 Years -	Karolinska University Hospital

Spots Global Cancer Trial Database for pam50

Every month we try and update this database with for pam50 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pam50

Every month we try and update this database with for pam50 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pam50 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.