Wednesday, September 20, 2023 MA32 secondary analysis: Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer Goodwin PJ, Chen BE, Gelmon KA, Whelan TJ, Ennis M, Lemieux J, Ligibel JA, Hershman DL, Mayer IA, Hobday TJ, Bliss JM, Rastogi P, Rabaglio-Poretti M, Thompson AM, Rea DW, Stos PM, Shepherd LE, Stambolic V, Parulekar WR. Effect of Metformin Versus Placebo on New Primary Cancers in Canadian Cancer Trials Group MA.32: A Secondary Analysis of a Phase III Randomized Double-Blind Trial in Early Breast Cancer (ONLINE). Journal of Clinical Oncology 2023. https://ascopubs.org/doi/abs/10.1200/JCO.23.00296 The MA.32 trial provided a unique opportunity to examine the effects of metformin on the risk of developing new primary invasive cancers in a population without diabetes. Metformin did not affect the risk of new contralateral breast cancer, any invasive cancer, cancers outside of the breast, obesity, or tobacco-associated cancers. Point estimates of risk were all above 1, making it unlikely that additional power would have identified a clinically important reduction in risk. Furthermore, metformin did not reduce cancer risk in subgroups defined by BMI, metabolic factors (insulin, HOMA, leptin, hsCRP), smoking history, or rs11212617 SNP status, factors that could potentially be associated with metformin benefit. Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer D. M. Jiang, S. Parshad, L. Zhan, H.-W. Sim, L. L. Siu, G. Liu, et al. Plasma Cetuximab Concentrations Correlate With Survival in Patients With Advanced KRAS Wild Type Colorectal Cancer (ONLINE). Clinical Colorectal Cancer, 2023. https://www.sciencedirect.com/science/article/pii/S1533002823000841 Background: Cetuximab is a standard of care therapy for patients with RAS wild-type (WT) advanced colorectal cancer. Limited data suggest a wide variation in cetuximab plasma concentrations after standard dosing regimens. We correlated cetuximab plasma concentrations with survival and toxicity. Results: Week 5 plasma cetuximab concentrations were available for 591 patients (78.8%). The median overall survival (OS) was 11.4 months and 7.8 months for patients in the highest (T3) and lowest tertiles (T1) respectively. On multivariable analysis, plasma cetuximab concentration was associated with OS (HR 0.66, 95% confidence interval [CI]: 0.53-0.83, P < .001, T3 vs. T1), and a trend towards progression-free survival (HR 0.82, 95% CI: 0.66-1.02, P = .07, T3 vs. T1). There was no association between cetuximab concentration and skin toxicity or diarrhea. Conclusion: The standard cetuximab dosing regimen may not be optimal for all patients. Further pharmacokinetic studies are needed to optimize cetuximab dosing given the potential improvement in OS.
