Paper Spotlight: Effects of Metformin and Rapamycin in Pancreatic Cancer

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Oncotarget

Oncotarget published this trending research paper on May 26, 2020, entitled, "An exploratory study of metformin with or without rapamycin as maintenance therapy after induction chemotherapy in patients with metastatic pancreatic adenocarcinoma" by researchers from the Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD; The Skip Viragh Center for Pancreas Cancer at Johns Hopkins, Baltimore, MD; Virginia Piper Cancer Center at HonorHealth, Scottsdale, AZ; Molecular Medicine Division, Translational Genomics Research Institute (TGen), Phoenix, AZ; Division of Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Department of Nuclear Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai City, China; The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD. Abstract: Purpose: Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). This phase 1b study (NCT02048384) was conducted to evaluate the feasibility and activity of metformin +/– rapamycin in the maintenance setting for unselected patients with metastatic PDA (mPDA) treated with chemotherapy. Materials and Methods: Eligible patients with stable or responding mPDA after ≥ 6 months on chemotherapy were randomized 1:1 to metformin alone (Arm A) or with rapamycin (Arm B), stratified by prior treatment with FOLFIRINOX. Fluorodeoxyglucose (FDG) PET scans and peripheral blood mononuclear cells were obtained for exploratory analyses. Results: 22 subjects (11 per arm) received treatment per protocol. Median PFS/OS were 3.5 and 13.2 months respectively, with 2 year OS rate of 37%; there were no differences between arms. No responses were observed by RECIST; however, decreases in FDG avidity and/or CA19-9 were observed in several long-term survivors. Treatment related adverse events of Grade ≥ 3 occurred in 0% vs 27% of patients in Arm A vs B and were asymptomatic hematologic or electrolyte abnormalities that were not clinically significant. Improved survival was associated with low baseline neutrophil: lymphocyte ratio, baseline lack of assessable disease by PET, and greater expansion of dendritic cells following treatment. Conclusions: Metformin +/– rapamycin maintenance for mPDA was well-tolerated and several patients achieved stable disease associated with exceptionally long survival. Further prospective studies are needed to clarify the role of these agents in the maintenance setting and to enhance patient selection for such approaches. Press release - https://www.oncotarget.com/news/pr/an-exploratory-study-of-metformin-and-rapamycin-as-maintenance-therapy/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27586 DOI - https://doi.org/10.18632/oncotarget.27586 Full text - https://www.oncotarget.com/article/27586/text/ Correspondence to - Dung T. Le - dle@jhmi.edu Keywords - pancreatic cancer, mTOR inhibition, maintenance therapy, metformin, rapamycin About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957