Everolimus exposure and early metabolic response as predictors for treatment outcomes in breast cancer patients treated with everolimus and exemestane.

Le résumé fourni par la source

1062 Background: Treating breast cancer patients (BC pts) with everolimus and exemestane can be challenging due to toxicity and suboptimal treatment responses. We investigated whether everolimus exposure, elderly age, and early metabolic response are predictive of toxicity and effectiveness in these pts. Methods: We collected blood samples from BC pts, 14 and 35 days after starting everolimus and exemestane, to measure everolimus trough level (Cmin). Toxicity, defined as dose interventions (reduction or discontinuation) < 3 months, and progression free survival (PFS) according to RECIST 1.1 were recorded. 18F-FDG-PET was performed at baseline, and 14 and 35 days after start of therapy. SUV normalized by lean body mass was calculated for the maximum voxel and highest peak (SULmax and SULpeak), for up to 5 target lesions. Results: In 44 evaluable pts, the geometric mean (GM) Cmin was higher in pts with dose interventions < 3 months compared to pts without: 17.4 vs 12.3 µg/L (p = .02). The optimal cut-off value to predict toxicity was Cmin > 19.2 µg/L (AUC 0.71, sensitivity 0.55, specificity 0.92). Elderly pts ( > 70 years) compared to pts < 70 years had a shorter median time to dose intervention: 42 vs 141 days (p = .001), but no significant difference in everolimus GM Cmin: 17.6 vs 13.5 µg/L (p = .12). GM Cmin of pts with and without progressive disease (PD) < 3 months was not significantly different: 12.0 µg/L vs 15.2 µg/L, respectively (p = .12). FDG-PET scans of 30 pts were analyzed. The percentage decrease in SULpeak of the lesion with highest avidity at day 14 (SULpeak high d14) was the best predictor of PD < 3 months. Pts with > 11% vs < 11% decrease in SULpeak high at d14 had a median PFS of 411 days vs 90 days respectively (p = .001), and 11 vs 70% of these pts had PD < 3 months. Conclusions: Our results show that everolimus toxicity is related to everolimus Cmin and by monitoring everolimus Cmin, toxicity might be prevented. We recommend diligent monitoring of elderly pts, as they have toxicity more frequently. No relation was observed between everolimus exposure and effectiveness. FDG-PET is able to early identify pts at high risk of early progression. Further validation of these results is required. Clinical trial information: NCT01948960.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.