A. W. J. M. Glaudemans

The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients

Background:The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[18F]fluoro-17β-oestradiol (FES) or 2-[18F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms.Methods:A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests.Results:The FES-PET/CT strategy decreased the number of biopsies by 39±9%, while upfront FDG-PET/CT increased the number of biopsies by 38±15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1±3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness.Conclusions:The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1±3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.

Abstract PD2-12: Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole

Palbociclib plus letrozole has improved both progression free survival and overall response rate in metastatic breast cancer (MBC) patients. For response to palbociclib, the best biomarker is ER expression. 16α-[ 18 F]Fluoro-17β-estradiol (FES) -PET allows whole body ER level assessment, and provides insight in the heterogeneity of ER expression throughout the body. We hypothesized that lesions with low uptake on FES-PET are unlikely to respond to letrozole plus palbociclib. METHODS : Post-menopausal women with ER positive MBC were eligible for this pilot study. All patients were staged with fludeoxyglucose (FDG)-PET and CT scan, and in addition a FES-PET was performed at baseline. After 8 weeks treatment an FDG-PET/CT was used for response evaluation. The primary endpoint was the relation between standard uptake value (SUV) per lesion on FES-PET to response, as measured by RECIST 1.1 criteria in case of measurable disease. In case of non-measurable bone lesions, progression was defined as an increase in SUV on FDG-PET of more than 30% per lesion compared to baseline (based on PERCIST). RESULTS: 15 patients were included of which 14 were evaluable for primary endpoint. Mean age was 50 years (range 35-76). Median number of prior therapies was 1. A total of 280 lesions were detected on conventional imaging of which 50 showed low uptake (SUV DISCUSSION: this pilot trial indicates negative predictive value of low FES uptake for response to letrozol plus palbociclib in ER positive MBC. The FES-PET may therefore be a biomarker for response for this combination treatment. This will have to be explored further in future clinical trials. Citation Format: Venema CM, de Vries EFJ, Glaudemans AWJM, Hospers GAP, Schroder CP. Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-12.

1627PPET-IMAGING WITH 89ZR-LABELED ANTI-MESOTHELIN (MSLN) ANTIBODY IN PATIENTS WITH PANCREATIC CANCER (PC) OR OVARIAN CANCER (OC)

Aim: The tumor antigen MSLN is frequently overexpressed in PC and OC. A 89Zr-PET study (NCT01832116) with MMOT0530A, an anti-MSLN antibody, was initiated in conjunction with a phase 1 study of the antibody-drug conjugate DMOT4039A (containing MMOT0530A linked to the anti-mitotic agent MMAE, NCT01469793). This imaging study aims to investigate antibody tumor uptake, whole body distribution and organ pharmacokinetics and to explore the relation between uptake and MSLN expression and response to DMOT40392A treatment in patients with unresectable PC or platinum-resistant OC. Methods: Before receiving DMOT4039A, patients were injected with 37 MBq 89Zr-MMOT0530A +/- additional unlabeled MMOT0530A, followed by PET/CT imaging 2, 4 and 7 days post injection (pi). Tracer uptake was quantified with standardized uptake value (SUV) and expressed as mean (±SD). MSLN expression was determined in archival tumor tissue with an exploratory immunohistochemical (IHC) assay. Results: 7 PC and 4 OC patients were included. MSLN expression varied from 0 to 3+. The optimal antibody protein dose resulting in sufficient circulating tracer was 10 mg MMOT0530A and the optimal imaging time was 4 or 7 days pi. Tumor tracer uptake was observed in 37 quantifiable tumor lesions (all patients) with mean SUV of 10.7 (±6.3) on PET 4 days pi. The mean SUV per patient (1-8 lesions/patient) was 10.9 (±5.7), with 9.2 (±4.5) in PC and 11.9 (±7.4) in OC lesions on PET 4 days pi. Within patients, a mean 2.4-fold (±1.10) difference in tumor uptake between lesions was found. Two measurable lesions on diagnostic CT (according to RECIST 1.1) were not visible on PET. Uptake in blood, liver, kidneys, spleen and intestine reflected normal antibody distribution with mean SUV at day 4 pi of 5.6, 7.8, 6.1, 4.1 and 3.2, respectively, while low uptake was observed in muscle, lung, brain and bone (0.6, 1.0, 0.2 and 0.7, respectively). Tracer tumor uptake was lower in the 2 patients with IHC scores 0 and 1. Best response on DMOT4039A was stable disease in ten patients. An association between iPET tumor uptake and clinical response could not be determined. Conclusions: 89Zr-MMOT0530A-PET shows antibody uptake in primary and metastatic PC and OC tumor lesions. This technique can potentially guide antibody-based therapy development.