Isabel Pimentel1, Ana Elisa Lohmann2, Marguerite Ennis3, Ryan J O Dowling4, David Cescon4, C Elser5, K R Potvin6, R Haq7, C Hamm6, Martin C Chang8, Vuk Stambolic4, Pamela J Goodwin2. 1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada. Electronic address: immpsp@gmail.com. 2. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada. 3. Applied Statistician, 9227, Kennedy Road, Markham; Ontario, Canada. 4. Princess Margaret Cancer Centre, University Health Network, Ontario, Canada. 5. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Ontario, Canada; Princess Margaret Cancer Centre, University Health Network, Ontario, Canada. 6. Western University, London, ON, Canada. 7. St. Michael's Hospital, University of Toronto, Toronto, ON, Canada. 8. Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, USA.
Abstract
OBJECTIVES: Pre-clinical data suggest metformin might enhance the effect of chemotherapy in breast cancer (BC). We conducted a Phase II randomized trial of chemotherapy plus metformin versus placebo in metastatic breast cancer (MBC). MATERIAL AND METHODS: In this double blind phase II trial we randomly assigned non-diabetic MBC patients on 1st to 4th line chemotherapy to receive metformin 850 mg po bid or placebo bid. Primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), response rate (RR), toxicity and quality of life (QOL). With 40 subjects and a type-one error of 0.2 (one-sided), a PFS hazard ratio (HR) of 0.58 could be detected with 80% power. RESULTS:40 patients were randomized (22 metformin, 18 placebo) with a mean age of 55 vs 57 years and ER/PR positive BC in 86.4% vs 83.3% off metformin vs placebo, respectively. Mean BMI was 27kg/m2 in both arms. The majority of patients were on 1st line chemotherapy. Grade 3-4 toxicity occurred in 31.8% (metformin) vs 58.8% (placebo). Best response: Partial response 18.2% metformin vs 25% placebo, stable disease 36.4% metformin vs 18.8% placebo, progressive disease 45.4% metformin vs 56.2% placebo. Mean PFS was 5.4 vs 6.3 months (metformin vs placebo), HR 1.2 (95% CI 0.63-2.31). Mean OS was 20.2 (metformin) vs 24.2 months (placebo), HR 1.68 (95% CI 0.79-3.55). CONCLUSION: In this population metformin showed no significant effect on RR, PFS or OS. These results do not support the use of metformin with chemotherapy in non-diabetic MBC patients.
RCT Entities:
OBJECTIVES: Pre-clinical data suggest metformin might enhance the effect of chemotherapy in breast cancer (BC). We conducted a Phase II randomized trial of chemotherapy plus metformin versus placebo in metastatic breast cancer (MBC). MATERIAL AND METHODS: In this double blind phase II trial we randomly assigned non-diabetic MBCpatients on 1st to 4th line chemotherapy to receive metformin 850 mg po bid or placebo bid. Primary outcome was progression-free survival (PFS); secondary outcomes included overall survival (OS), response rate (RR), toxicity and quality of life (QOL). With 40 subjects and a type-one error of 0.2 (one-sided), a PFS hazard ratio (HR) of 0.58 could be detected with 80% power. RESULTS: 40 patients were randomized (22 metformin, 18 placebo) with a mean age of 55 vs 57 years and ER/PR positive BC in 86.4% vs 83.3% off metformin vs placebo, respectively. Mean BMI was 27kg/m2 in both arms. The majority of patients were on 1st line chemotherapy. Grade 3-4 toxicity occurred in 31.8% (metformin) vs 58.8% (placebo). Best response: Partial response 18.2% metformin vs 25% placebo, stable disease 36.4% metformin vs 18.8% placebo, progressive disease 45.4% metformin vs 56.2% placebo. Mean PFS was 5.4 vs 6.3 months (metformin vs placebo), HR 1.2 (95% CI 0.63-2.31). Mean OS was 20.2 (metformin) vs 24.2 months (placebo), HR 1.68 (95% CI 0.79-3.55). CONCLUSION: In this population metformin showed no significant effect on RR, PFS or OS. These results do not support the use of metformin with chemotherapy in non-diabetic MBCpatients.
Authors: Pamela J Goodwin; Bingshu E Chen; Karen A Gelmon; Timothy J Whelan; Marguerite Ennis; Julie Lemieux; Jennifer A Ligibel; Dawn L Hershman; Ingrid A Mayer; Timothy J Hobday; Judith M Bliss; Priya Rastogi; Manuela Rabaglio-Poretti; Som D Mukherjee; John R Mackey; Vandana G Abramson; Conrad Oja; Robert Wesolowski; Alastair M Thompson; Daniel W Rea; Paul M Stos; Lois E Shepherd; Vuk Stambolic; Wendy R Parulekar Journal: JAMA Date: 2022-05-24 Impact factor: 157.335
Authors: Ngozi D Akingbesote; Aaron Norman; Wanling Zhu; Alexandra A Halberstam; Xinyi Zhang; Julia Foldi; Maryam B Lustberg; Rachel J Perry Journal: Commun Biol Date: 2022-05-20
Authors: Stephanie P Totten; Young Kyuen Im; Eduardo Cepeda Cañedo; Ouafa Najyb; Alice Nguyen; Steven Hébert; Ryuhjin Ahn; Kyle Lewis; Benjamin Lebeau; Rachel La Selva; Valérie Sabourin; Constanza Martínez; Paul Savage; Hellen Kuasne; Daina Avizonis; Nancy Santos Martínez; Catherine Chabot; Adriana Aguilar-Mahecha; Marie-Line Goulet; Matthew Dankner; Michael Witcher; Kevin Petrecca; Mark Basik; Michael Pollak; Ivan Topisirovic; Rongtuan Lin; Peter M Siegel; Claudia L Kleinman; Morag Park; Julie St-Pierre; Josie Ursini-Siegel Journal: Nat Commun Date: 2021-06-03 Impact factor: 17.694
Authors: Pamela J Goodwin; Ryan J O Dowling; Marguerite Ennis; Bingshu E Chen; Wendy R Parulekar; Lois E Shepherd; Margot J Burnell; Rachel Vander Meer; Andrea Molckovsky; Anagha Gurjal; Karen A Gelmon; Jennifer A Ligibel; Dawn L Hershman; Ingrid A Mayer; Timothy J Whelan; Timothy J Hobday; Priya Rastogi; Manuela Rabaglio-Poretti; Julie Lemieux; Alastair M Thompson; Daniel W Rea; Vuk Stambolic Journal: NPJ Breast Cancer Date: 2021-06-08