Abstract CT075: Tumor mutation status will predict metabolic response to metformin in lung cancer treated with stereotactic body radiation therapy (SBRT)

At present, there are over 100 clinical trials examining the role of metformin in malignancy, either alone or in combination with chemotherapy. However, despite significant preclinical data, trials examining the role of metformin as a radiosensitizer are few. Moreover, the effects of endogenous tumor mutations on response to metformin are unknown, as some data suggests that certain mutations (eg. TP53, STK11) may confer sensitivity to this agent. Finally, the effects of metformin on FDG-uptake in solid tumors is far from clear, as this agent can actually lead to an increased uptake of FDG in normal bowel. Because of these questions, we have designed an imagining-guided trial of 70 patients, randomized 6:1 in favor of metformin treatment in patients with non-small cell lung cancer to be treated with stereotactic body radiotherapy (SBRT). Patients receive either placebo or metformin at a loading dose of 1,000 mg per day for one week followed by 1-2 weeks of metformin at 2,000 mg per day. Prior to study entry, an FDG-PET scan is performed which is then repeated after 2-3 weeks of metformin treatment. Metformin or placebo is maintained throughout SBRT and the standard daily cone-beam CTs are taken. Metformin or placebo stops at the end of SBRT followed by an additional FDG-PET scan 6 months after completion of therapy. All tumors with available tissue will be subjected to targeted sequencing. The primary outcome is FDG-PET response following initial metformin or placebo monotherapy as well as at 6 months. Secondary outcomes include the effect of common mutations (TP53, STK11, Kras) on metformin FDG-PET response. Currently, 14 patients have been registered for this trial. We anticipate that this study will provide a unique insight on how metformin affects FDG-PET response, if this response is affected by tumor mutation status, and provide preliminary data on the clinical efficacy of metformin in the setting of SBRT. Citation Format: Heath D. Skinner, Thomas Guerrero, Brian Hobbs, Laurence Court, Paige L. Nitsch, John Heymach. Tumor mutation status will predict metabolic response to metformin in lung cancer treated with stereotactic body radiation therapy (SBRT). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT075.