Abstract P1-19-22: Pearl or the use of FDG positron emission tomography imaging as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer
Authors: Gombos Andrea , Piccart-Gebhart Martine , Ameye Lieveke , Vuylsteke Peter , Neven Patrick , Richard Vincent , Duhoux Francois P , Paesmans Marianne , Ignatiadis Michail , Flamen Patrick , Gebhart Géraldine 
Published: March 2020

Abstract
Background: The combination of everolimus and an endocrine agent has shown a progression-free survival (PFS) benefit but also significant toxicity in locally advanced and/or metastatic breast cancer (MBC) patients. Disappointingly, all translational research efforts conducted so far on primary/metastatic tissue or baseline ctDNA samples have failed to identify clinically useful biomarkers of benefit with the possible exception of p4EBP1 which requires fresh metastatic biopsies (Bachelot at al, ASCO 2019).
Methods: Forty-seven patients were included in the PEARL trial in six Belgian centres. All patients underwent one baseline and one “early” 18FDG-PET/CT on day 14 (blinded to the treating oncologist) after treatment initiation. Eligible patients had prior progression on NSAI and at least one measurable lesion on baseline 18FDG-PET/CT (fulfilling PERCIST). Twenty seven of the 47 patients were treated in a pilot phase aiming to characterize 18FDG-PET/CT metabolic responses 14 and 28 days after treatment initiation. Day 14 18FDG-PET/CT was selected for the second phase in which 20 more patients were included to answer the primary endpoint of the trial, namely the potential of an early FDG-PET/CT to select patients who will not derive a long-term benefit from everolimus-exemestane combination. We considered as “metabolic responders” those patients in whom at least a 25% homogenous decrease in SUVmax was seen in all their target lesions; the so called “consistent” patient-based response, here correlated to PFS.
Results: Seventy-four percent of the patients had visceral metastasis, 26% were pretreated with CDK 4/6 inhibitors and 58% with at least one line of chemotherapy (28% ≥ 2 lines) for the treatment of MBC. Metabolic non-response rate on day 14 was 64%. Two patients were considered non-evaluable because they stopped everolimus 3 and 8 days before early 18FDG-PET/CT respectively. The median PFS in non-responding patients was 2.3 months compared to 6 months in those who showed a consistent metabolic response (HR-1.96, 95%CI: 0.98-3.95, p=0.05). We’ll be able to assess whether day 14 ctDNA measurements add predictive value to imaging.
Conclusion: Absence of 18FDG-PET/CT metabolic response after 14 days of everolimus-exemestane combination is associated with a low probability to derive benefit from this treatment. The advanced stage of the patients included in this trial (75% visceral metastasis) and their extensive prior treatments can explain the poorer outcome seen with exemestane-everolimus compared to the Bolero2 trial.
Citation Format: Andrea Gombos, Martine Piccart-Gebhart, Lieveke Ameye, Peter Vuylsteke, Patrick Neven, Vincent Richard, Francois P Duhoux, Marianne Paesmans, Michail Ignatiadis, Patrick Flamen, Géraldine Gebhart. Pearl or the use of FDG positron emission tomography imaging as an early dynamic biomarker of everolimus efficacy in advanced luminal breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-22.