Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial

BackgroundTriple negative breast cancer (TNBC) is more prevalent among the younger age group and is the most aggressive form. Women with TNBC phenotype have 19% lower 5-year overall survival and 18% lower disease-free survival than their non-TNBC counterparts (1). Hence, extensive research is essent...

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Main Authors: Vinod K. Ramani, Ajaikumar Basavalinga Sadashivaiah, Radheshyam Naik
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1561692/full
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author Vinod K. Ramani
Ajaikumar Basavalinga Sadashivaiah
Radheshyam Naik
author_facet Vinod K. Ramani
Ajaikumar Basavalinga Sadashivaiah
Radheshyam Naik
author_sort Vinod K. Ramani
collection DOAJ
description BackgroundTriple negative breast cancer (TNBC) is more prevalent among the younger age group and is the most aggressive form. Women with TNBC phenotype have 19% lower 5-year overall survival and 18% lower disease-free survival than their non-TNBC counterparts (1). Hence, extensive research is essential for the development of treatment modalities with high efficacy. Metformin is a widely used anti-diabetic drug. The research work has potential implications for re-purposing metformin in the clinical management of TNBC.MethodsThe study design includes a phase 2 randomized clinical trial of TNBC, with metformin given for the intervention arm and placebo oral tablet for the non-intervention arm. A total of 418 breast cancer patients are randomized with a parallel assignment model (209 each for the intervention and the control arms). This is an open-label trial where the primary purpose is treatment and adheres to the SPIRIT reporting guidelines. The trial will be initiated during January 2025 and is expected to be completed by May 2027.DiscussionThe clinical benefit, pathological response rate, and radiological response will be measured after 4.5 to 6 months of initiating treatment. The study will assess the recurrence-free survival (at intervals of 6 months) and overall survival at 2 years from treatment initiation. Patients who respond to the intervention are expected to have >50% decrease in the size of the primary tumor without the appearance of new lesions. RECIST v1.1 criteria are used to determine the objective tumor response for target lesions.
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spelling doaj-art-b7545ba68bdb42faae61c347e81664622025-08-20T03:15:56ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15616921561692Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trialVinod K. Ramani0Ajaikumar Basavalinga Sadashivaiah1Radheshyam Naik2Preventive Oncology, Healthcare Global, Bangalore, IndiaDept. of Radiation Oncology, Healthcare Global, Bangalore, IndiaMedical Oncology, Healthcare Global, Bangalore, IndiaBackgroundTriple negative breast cancer (TNBC) is more prevalent among the younger age group and is the most aggressive form. Women with TNBC phenotype have 19% lower 5-year overall survival and 18% lower disease-free survival than their non-TNBC counterparts (1). Hence, extensive research is essential for the development of treatment modalities with high efficacy. Metformin is a widely used anti-diabetic drug. The research work has potential implications for re-purposing metformin in the clinical management of TNBC.MethodsThe study design includes a phase 2 randomized clinical trial of TNBC, with metformin given for the intervention arm and placebo oral tablet for the non-intervention arm. A total of 418 breast cancer patients are randomized with a parallel assignment model (209 each for the intervention and the control arms). This is an open-label trial where the primary purpose is treatment and adheres to the SPIRIT reporting guidelines. The trial will be initiated during January 2025 and is expected to be completed by May 2027.DiscussionThe clinical benefit, pathological response rate, and radiological response will be measured after 4.5 to 6 months of initiating treatment. The study will assess the recurrence-free survival (at intervals of 6 months) and overall survival at 2 years from treatment initiation. Patients who respond to the intervention are expected to have >50% decrease in the size of the primary tumor without the appearance of new lesions. RECIST v1.1 criteria are used to determine the objective tumor response for target lesions.https://www.frontiersin.org/articles/10.3389/fonc.2025.1561692/fullmetforminsurvival analysistriple negative breast neoplasmremissionneoadjuvant
spellingShingle Vinod K. Ramani
Ajaikumar Basavalinga Sadashivaiah
Radheshyam Naik
Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
Frontiers in Oncology
metformin
survival analysis
triple negative breast neoplasm
remission
neoadjuvant
title Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
title_full Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
title_fullStr Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
title_full_unstemmed Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
title_short Neoadjuvant chemotherapy with or without metformin in early-stage or locally advanced (non-metastatic) triple negative breast cancer—an open-label phase 2 randomized controlled trial
title_sort neoadjuvant chemotherapy with or without metformin in early stage or locally advanced non metastatic triple negative breast cancer an open label phase 2 randomized controlled trial
topic metformin
survival analysis
triple negative breast neoplasm
remission
neoadjuvant
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1561692/full
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AT ajaikumarbasavalingasadashivaiah neoadjuvantchemotherapywithorwithoutmetformininearlystageorlocallyadvancednonmetastatictriplenegativebreastcanceranopenlabelphase2randomizedcontrolledtrial
AT radheshyamnaik neoadjuvantchemotherapywithorwithoutmetformininearlystageorlocallyadvancednonmetastatictriplenegativebreastcanceranopenlabelphase2randomizedcontrolledtrial