Molecular Alterations Associated With Resistance to Endocrine Therapy and Impacting Treatment With mTOR Inhibitor

Conditions

Metastatic Breast Cancer

Keywords

Failed non steroidal aromatases inhibitors, Eligible for everolimus+exemestane

Brief summary

This is a prospective biomarker study to show that p4EBP1 staining predicts clinical benefit from treatment with everolimus in patients who are eligible for everolimus+exemestane treatment. This trial is not aimed at evaluating a drug activity. Everolimus and exemestane are prescribed within their approved indication as per usual practice and are not part of this trial.

Detailed description

Estrogen hormone receptor-positive metastatic breast cancer who failed to non steroidal aromatases inhibitors in patients who are eligible for everolimus+exemestane treatment

Barraud S, Vacher S, Schiffler C, Wong J, Hamza A, Courtois L, Pinton A, Servant N, Baulande S, Attignon V, Soubeyran I, Rouleau E, Coussy F, Campone M, Legrand F, Jimenez M, André F, Bachelot T, Bièche I.

2025-06-12

10.1038/s41416-025-03083-5

p4EBP1 staining predicts outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane.

Vanacker H, Treilleux I, Schiffler C, Bieche I, Campone M, Patsouris A, Arnedos M, Cottu PH, Jacquin JP, Dalenc F, Pinton A, Servant N, Attignon V, Rouleau E, Morel A, Legrand F, Jimenez M, Andre F, Bachelot T.

2024-01-052 citations

10.1038/s41416-023-02549-8

mTORC1 activation assessed in metastatic sample to predict outcome in patients with metastatic breast cancer treated with everolimus-exemestan: Results from the SAFIRTOR study.

Thomas Bachelot, Isabelle Treilleux, Camille Schiffler, Ivan Bièche, Mario Campone et al. (16 authors)

Journal of Clinical Oncology2019-05-206 citations

10.1200/jco.2019.37.15_suppl.1024

An open-label, phase II study of rucaparib, a PARP inhibitor, in HER2- metastatic breast cancer patients with high genomic loss of heterozygosity.

Anne Patsouris, Olivier Trédan, L. Campion, Anthony Gonçalvès, Mónica Arnedos et al. (15 authors)

Journal of Clinical Oncology2018-05-205 citations

10.1200/jco.2018.36.15_suppl.tps1112

Interventions

PROCEDUREBiopsy

biopsy of a metastasis

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

SCREENING

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

\- Eligible for everolimus+exemestane treatment as required by the marketing authorisation conditions 1. Women (or men) with histologically-proven Estrogen Receptor-positive (ER+) and/or Progesterone Receptor-positive (PR+) / Human Epidermal growth factor Receptor 2-negative (HER2-) metastatic breast adenocarcinoma or locally advanced disease who cannot be treated with surgery and/or radiation therapy 2. Postmenopausal women 3. Asymptomatic if visceral disease 4. Second line hormonotherapy or more for metastatic or locally advanced disease after recurrence or progression following a non-steroidal aromatase inhibitor (in adjuvant or metastatic setting) \- Eligible for the biopsy 5. Progressive disease under endocrine therapy at the time of inclusion 6. Treatment with everolimus and exemestane not yet started 7. Patients with metastases that can be biopsied, except bone metastases 8. Measurable or evaluable disease 9. Age ≥18 years 10. WHO Performance Status 0/1 11. Provision of signed and dated, written informed consent prior to any protocol specific procedure, including biopsy 12. Patient with social insurance coverage

Exclusion criteria

1. Contraindications for everolimus+exemestane treatment 2. Previous treatment with an anti-mTOR therapy 3. More than 1 previous line of chemotherapy in metastatic setting 4. Life expectancy \<3 months 5. Spinal cord compression and/or symptomatic or progressive brain metastases (unless asymptomatic or treated and stable off steroids for at least 30 days prior to start of study drug) 6. Haematopoietic function or organ impairment as shown by the following criteria: * Polynuclear neutrophils \<1.5 x 10⁹/L * Platelets \<100 x 10⁹/L * Haemoglobin \<90 g/L * Alanine aminotransferase (ALAT) / aspartate aminotransferase (ASAT) \>2.5 x ULN in the absence of or \>5 x upper limit of normal (ULN) in the presence of liver metastases * Bilirubin \>1.5 x ULN * Creatinine clearance ≤50 mL/min (measured or calculated by Cockcroft and Gault formula) * Calcium and phosphate \>ULN 7. Abnormal coagulation or any other medical situation contraindicating biopsy 8. Bone metastases when this is the only site of biopsiable disease 9. Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol 10. Individuals deprived of liberty or placed under the authority of a tutor

Design outcomes

Primary

Measure	Time frame	Description
the predictive value of p4EBP1 for an mTOR inhibitor efficacy	from inclusion up to 6 months	The primary endpoint of the trial is the predictive value of p4EBP1 for an mTOR inhibitor efficacy, measured by the association between expression level of the biomarker (high vs low expression with a cutoff value set at the median percentages of marked cells) and clinical benefit after 6 months of everolimus+exemestane treatment.

Countries

France

Outcome results

None listed