Expert Review The Role of Molecular Imaging in Response Prediction in Metastatic Breast Cancer

Transcription

1 Expert Review The Role of Molecular Imaging in Response Prediction in Metastatic Breast Cancer Geraldine Gebhart, MD Institut Jules Bordet Brussels, Belgium Discussants Moderator Lee Lokey, MD prime Oncology Atlanta, Georgia, United States Alessandra Gennari, MD, PhD Galliera Hospital Genoa, Italy

2 Early Stages Advanced Stages Negative Nodes Positive Nodes Stage 1 Stage 2 Stage 3 Stage 4 Primary Tumor Luminal HER2+ Triple-Neg Luminal Metastases???? HER2+ Triple-Neg Biopsy: - Not always feasible - Not always contributive - Reliable for the entire disease burden? (Heterogeneity)

3 Potential Role of Molecular Imaging Molecular characterization of metastatic lesions Response prediction to (targeted) therapies Examples: Fluorestradiol (FES) PET/CT 89 Zr-trastuzumab PET/CT PD-L1 imaging: UNDER DEVELOPMENT PD-L1, Programmed death-ligand 1; PET/CT, positron emission tomography/computed tomography

4 Visualization Estrogen Receptor (ER) Courtesy of E. De Vries

5 16α-[18F]-Fluoro-17β-Estradiol (FES) PET Tracer for ER Imaging Estradiol Good correlation between FES uptake & ER expression immunohistochemically FES tumor uptake predictive for response to anti-hormone therapy. Low FES uptake no response FES F * Peterson LM, et al. J Nucl Med. 2008;49(3): Linden HM, et al. J Clin Oncol. 2006;24(18): van Kruchten M, et al. Lancet Oncol. 2013;14(11):e465-e475.

6 Monitoring Fulvestrant Effects on Tumor ER Courtesy of E. De Vries

7 Excellent Blockade FES Uptake Bad Blockade FES Uptake Heterogenous Blockade FES Uptake Baseline Day 28 Fulvestrant FES PET FES PET FES PET van Kruchten M, et al. Cancer Disc. 2015;5(1):72-81.

8 Change FES-Uptake From Baseline, % Waterfall Plot: Changes in Tumor FES-Uptake Before & During Fulvestrant (Day 28) of All Patients Clinical benefit Progressive disease Not evaluable Corrected for tamoxifen Prior tamoxifen van Kruchten M, et al. Cancer Disc. 2015;5(1):72-81.

9 16α-[18F]-Fluoro-17β-Estradiol (FES) PET Tracer for Assessment of Endocrine Responsiveness All enrolled ER+ MBC pts n = F-FES CT/PET SUV 18F-FES 2 SUV 18F-FES <2 R Endocrine therapy (physician choice), until PD ARM A - Control Endocrine therapy until PD ARM B - Exp CT or ET + biologic agent until PD Pts Included in the Analysis N o Pts % Group A Group B Group C Group D 18FDG+/18FES+ 100% 100% 18FDG+/18FES+ 100% 50% 18FDG+/18FES+ 100% 25% 18FDG+/18FES- 100% 0% Gennari A, et al. Ann Oncol. 2017;28(Suppl 5): Abstract 114P. 53/ % 11/ % 5/79 6.3% 10/ %

10 16α-[18F]-Fluoro-17β-Estradiol (FES) PET Tracer for Assessment of Endocrine Responsiveness GROUP A 18 FDG 18F-FES GROUP C GROUP B 18 FDG 18F-FES GROUP D HR for PD in B,C,D treated with ET vs A 1.79 (P =.2) Targeting the endocrine pathway in heterogenous disease may not be ideal, CT could be needed upfront 18 FDG 18F-FES 18 FDG 18F-FES Gennari A, et al. Ann Oncol. 2017;28(Suppl 5): Abstract 114P. The long suffering ET-FES EU Group

11 Courtesy of E. De Vries Visualization HER2

12 Different Ways to Image the Disease HETEROGENEITY FDG HER2

13 FDG HER2 FDG HER2 A B HER2 PET Classification FDG HER2 FDG HER2 C D Gebhart G, et al. Ann Oncol. 2015;27(4):

14 Time to Treatment Failure (TTF) TTF: Time From Start of T-DM1 Until Its Discontinuation 89 Zr-Trastuzumab PET/CT 11.2 months Positive patterns Negative patterns 3.5 months HR % CI ; P<.0001 Gebhart G, et al. Ann Oncol. 2015;27(4):

15 Visualization PD-L1 Tracers are under development in Groeningen (NL) and Parma (IT)

16 Conclusion Molecular imaging has significantly improved over the past years Innovative PET tracers, such as 18F-FES and Zr-trastuzumab are being used in clinical trials to evaluate in vivo the presence and binding capacity of ER/HER2 in breast cancer tissue, simultaneously in the different metastatic sites New PET tracers targeting the immune checkpoint PD-1/PD-L1 to better characterize the immunoprofile in the different metastatic sites are under development This CT/PET-based technology is now available in many clinical centers and, combined with tissue/plasma biomarkers, can represent a step forward in the field of treatment individualization