ESMO Virtual Congress 2020: Invited Discussant: (617MO) Repurposing Metformin as Anticancer Drug (MANSMED) and (618MO) Local Therapy to the Primary Tumour for Newly Diagnosed, Oligo-Metastatic Prostate Cancer

( Dr. Noel Clarke first discussed presentation 617, the MANSMED trial. He reviewed the trial schemia, which randomized 124 high-risk prostate cancer patients 1:1 to either standard of care or standard of care plus metformin.


Dr. Clarke then discussed the rationale for combining metformin with standard of care. He presented data from a systematic review and meta-analysis published in 2012 showing that across multiple cancer contexts, diabetic patients taking metformin had lower cancer incidence and mortality.

Looking at prostate cancer specifically within the meta-analysis, the data was suggestive of decreased prostate cancer incidence in diabetic patients taking metformin.

Mechanistically, metformin promotes AMPK signaling, which abrogates catabolic metabolic elements and impedes signaling that could promote prostate cancer invasion and progression. 

The data presented in abstract 617 are suggestive of benefit in the metformin arm with regards to time to progression to CRPC, but numbers are small in each arm (62). In addition to the larger study ongoing with the authors of abstract 617, Arm K of the STAMPEDE study has recruited 2200 patients to standard of care therapy + metformin. Together, these studies will hopefully help answer the question of the utility of metformin in prostate cancer care.

Dr. Clarke then focused on abstract 618, a prospective randomized trial of local therapy to the prostate in combination with androgen deprivation therapy in low-volume/oligometastatic prostate cancer. As has been published from the STAMPEDE trial, radiotherapy to the prostate in the patient subgroup with low-metastatic burden (less than 4 bone mets, none outside vertebral bodies or pelvis, and no visceral metastases) conferred a survival advantage relative to standard of care alone. In a previously presented analysis of overall survival by number of bone metastases, addition of RT trends towards improved survival up until 4 bone metastases.


Dr. Clarke then reviewed the trial schema. Patients were balanced between groups (ADT versus ADT + local therapy). The majority of patients received prostatectomy as local therapy. At 28 months of follow-up, Dr. Clarke noted that the difference between the two arms were striking though he felt that the numbers were still low to generate substantial conclusions.



Larger studies to prospectively evaluate the role of local therapy are planned within Arm M of the STAMPEDE trial, which is shown below.


Presented by: Noel Clarke, MBBS, FRCS, ChM, FRCS, Professor of Urological Oncology, The Christie and Salford Royal Hospitals, Manchester, United Kingdom 

Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.

Related Content: 
Treating the Primary in High vs Low Volume Hormone Sensitive Disease - Interview Noel Clarke
APCCC 2019: Local Treatment of The Primary (Surgery) in the Metastatic Situation