2018 ASCO Annual Meeting!
Session: Genitourinary (Prostate) Cancer
Type: Poster Session
Time: Saturday June 2, 1:15 PM to 4:45 PM
Location: Hall A
Expression of immune checkpoints (ICs) on circulating tumor cells (CTCs) in men with metastatic prostate cancer (mPC).
Genitourinary (Prostate) Cancer
2018 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #286)
J Clin Oncol 36, 2018 (suppl; abstr 5059)
Author(s): Tian Zhang, Rebecca Garland Austin, Sally E Park, Daniella Runyambo, Rengasamy Boominathan, Chandra Rao, Elizabeth Bronson, Monika Anand, Patrick Healy, Daniel J. George, Megan Ann McNamara, Andrew J. Armstrong; Duke University Medical Center, Durham, NC; Emory University School of Medicine, Atlanta, GA; Albert Einstein College of Medicine, New York, NY; Duke Cancer Institute, Duke University, Durham, NC; Veridex LLC, Huntingdon Valley, PA; Duke University, Durham, NC; Duke University Medical Center, Mornsville, NC
Background: Most immune checkpoint inhibitors have shown limited efficacy in unselected men with mPC, and there is limited understanding about which ICs are relevant in mPC. We evaluated ICs on the cell surface of CTCs in patients (pts) with mPC. Methods: Pts were enrolled prospectively at the Duke Cancer Center in three cohorts: A) metastatic castration resistant prostate cancer (mCRPC) starting abiraterone acetate (AA) or enzalutamide (enza), B) mCRPC after AA or enza, and C) metastatic hormone sensitive PC (mHSPC). The Cellsearch platform was used to capture EpCAM- and CK-expressing CTCs and analyzed for PD-L1, PD-L2, B7-H3, and CTLA-4 expression at baseline, 12 weeks, and disease progression. Results: Through December 2017, we enrolled 18 pts (6 in cohort A, 8 in cohort B, and 4 in cohort C). CTCs were detectable in every cohort. At baseline, B7-H3 was the most prevalent IC while the other ICs were detected less frequently (Table 1). PD-L1 expression on CTCs was heterogeneous between and within pts; PD-L1 expression also changed during treatment and upon disease progression (Table 1). Rare CTCs expressed CTLA-4 and PD-L2, mostly in cohort B. Conclusions: Patients with mPC have detectable and heterogeneous ICs on CTCs, particularly PD-L1 and B7-H3, which can be monitored over time. B7-H3 was the most prevalent IC on CTCs, regardless of disease state. Our preliminary data suggest that pts with mCRPC post-enza/AA have higher levels of IC expression on CTCs compared with pts with mHSPC and mCRPC prior to enza/AA. We found evidence for heterogeneous CTC expression of CTLA-4 and PD-L2, particularly in men with mCRPC post-AA/enza.
|Median (range) of CTCs at baseline/week 12/PD||PD-L1 (%) baseline/week 12/PD||PD-L2 (%) baseline/week 12/PD||CTLA-4 (%) baseline/week 12/PD||B7-H3 (%) baseline/week 12/PD|
|A: mCRPC pre AA/enza||16 (0-59)/6 (0-50)/31 (16-49)||7/4/8||1/2/1||0/0/0||92/53/66|
|B: mCRPC post AA/enza||4 (0-54)/1 (0-4)/3 (0-108)||25/17/9||3/50/0||15/50/1||98/80/94|
|C: mHSPC||3 (0-52)/0 (0-1)/NE||11/100/NE||6/NE/NE||3/NE/NE||68/NE/NE|
NE: Not evaluable; PD: disease progression