Abstract 2226
Background
We report secondary and exploratory analysis with 18F-NaF PET/CT and CTCs to determine how tumour burden and RNA expression of androgen receptor (AR) splice variants and neuroendocrine (NE) features predict duration of treatment (DoTx) with ENZA.
Methods
Men with progressive mCRPC with ≥ 2 lesions on bone scintigraphy were enrolled and treated with ENZA 160 mg daily at 3 US sites. 18F-NaF PET/CT scans were obtained at baseline (BL) (PET1), week 13 (PET2), and at the time of PSA progression (per PCWG2 criteria), standard radiographic or clinical progression, or at 2 years without progression (PET3) using QTBI. CTCs were obtained at BL and at PET3. PSA decline and DoTx were compared with BL QTBI, CTC metrics, and change in QTBI.
Results
23 men (median age, 72 years [range, 51-93]; median PSA, 20.5 ng/mL [range, 3.9-133.6]) were enrolled; 22 of which completed planned imaging. The mean number of bone lesions on PET1 was 58 (range 9-168), with a median total standardized uptake value (SUVtotal) of 3886.5 (range 506.7-22852.8). DoTx ranged from 1.4 to 31.8+ mo. In general, SUV metrics decreased while on ENZA (PET2) and increased by PET3. Change in lesion heterogeneity (PET1 to PET3) was the most significant predictor of time to PSA progression (hazard ratio, 3.88; 95% confidence interval, 1.24-12.1). ARV7/9 was found in CTCs in 3/20 men and NE features were found in 4/20 men at BL and in 4/19 and in 11/19 men, respectively, at PET3.
Conclusions
Although PSA response with ENZA is high, DoTx is variable. SUVtotal at BL did not correlate with DoTx; however, decrease in SUVtotal/mean was associated with increased DoTx, with less heterogeneity correlating with a longer time to PSA progression. ARV7/9 or NE expression in CTCs did not predict lack of benefit from ENZA; however, at the time of progression, the observed increase in ARV7/9 and NE expression are consistent with tumor evolution to more aggressive phenotypes. While BL heterogeneity may be prognostic, it may not predict response or DoTx. Assessing response heterogeneity may predict response duration, thus, should be explored as a possible surrogate of benefit in future studies.
Clinical trial identification
NCT02384382.
Editorial acknowledgement
Medical writing and editorial assistance funded by Pfizer Inc. and Astellas Pharma, Inc. was provided by Stephanie Vadasz, PhD, and Michele Salernitano from Ashfield Healthcare Communications.
Legal entity responsible for the study
Pfizer Inc. and Astellas Pharma, Inc.
Funding
Pfizer Inc. and Astellas Pharma, Inc.
Disclosure
G. Liu: Leadership role, Shareholder / Stockholder / Stock options, Employee: AIQ Solutions; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Novartis; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (self), Research grant / Funding (institution): TRACON Pharma; Research grant / Funding (self), Research grant / Funding (institution): Madison Vaccines Inc.; Research grant / Funding (self), Research grant / Funding (institution): Pfizer Inc. C.E. Kyriakopoulos: Advisory / Consultancy, Travel / Accommodation / Expenses: Exelixis; Speaker Bureau / Expert testimony: The France Foundation; Research grant / Funding (self), Research grant / Funding (institution): Sanofi. J.M. Lang: Shareholder / Stockholder / Stock options, Licensing / Royalties, I am listed on the patent on a technology for rare cell capture and analysis. This technology has been licensed by Salus Discovery, LLC though no commercial products are available: Salus Discovery; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Agensys; Research grant / Funding (institution): Pfizer Inc.; Research grant / Funding (institution): Novartis. E.I. Heath: Advisory / Consultancy, Research grant / Funding (institution): Agensys; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Dendreon; Honoraria (self), Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): Tokai Pharmaceuticals; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Inovio Pharmaceuticals; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Zenith Epigenetics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Esanik; Research grant / Funding (institution): Oncolys BioPharma; Research grant / Funding (institution): CureMeta; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): eFFECTOR Therapeutics; Research grant / Funding (institution): Fortis. S. Perlman: Research grant / Funding (institution): GE Healthcare Progenics; Advisory / Consultancy: Pfizer Inc. T. Mayer: Advisory / Consultancy: Beacon Biosciences/ICON Medical; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Research grant / Funding (institution): Sotio; Research grant / Funding (institution): Merck; Research grant / Funding (self): Pfizer Inc. K. Modelska: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Employee: Pfizer Inc. A. Porcari: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Employee: Pfizer Inc. W. Duggan: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Employee: Pfizer Inc. R. Jeraj: Licensing / Royalties, Patents: Wisconsin Alumni Research Foundation; Shareholder / Stockholder / Stock options: AIQ Solutions; Research grant / Funding (institution): GE Healthcare. All other authors have declared no conflicts of interest.
Resources from the same session
2664 - Phase (Ph) II study of MBG453 + spartalizumab in patients (pts) with non-small cell lung cancer (NSCLC) and melanoma pretreated with anti–PD-1/L1 therapy
Presenter: Nicholas Mach
Session: Poster Display session 3
Resources:
Abstract
1285 - Preliminary results of STELLAR-001, a dose escalation phase I study of the anti-C5aR, IPH5401, in combination with durvalumab in advanced solid tumors.
Presenter: Christophe Massard
Session: Poster Display session 3
Resources:
Abstract
3808 - GOLFIG chemo-immunotherapy in metastatic colorectal cancer (mCRC) patients: A fifteen year retrospective analysis
Presenter: Pierpaolo Correale
Session: Poster Display session 3
Resources:
Abstract
5677 - Immune correlates in peripheral blood samples in a preoperative window of opportunity randomized trial of nivolumab with or without tadalafil in resectable squamous cell carcinoma of the head and neck (SCCHN)
Presenter: Larry Harshyne
Session: Poster Display session 3
Resources:
Abstract
4854 - Phase 1 evaluation of AB928, a novel dual adenosine receptor antagonist, combined with chemotherapy or AB122 (anti-PD-1) in patients (pts) with advanced malignancies
Presenter: John Powderly
Session: Poster Display session 3
Resources:
Abstract
4344 - Phase 1 Trial of CV301 in Combination with Anti-PD-1 Therapy in Non-squamous NSCLC
Presenter: Arun Rajan
Session: Poster Display session 3
Resources:
Abstract
4555 - Safety and efficacy results of the combination of DPX-Survivac, pembrolizumab and intermittent low dose cyclophosphamide (CPA) in subjects with advanced and metastatic solid tumors: preliminary results from the hepatocellular carcinoma (HCC), NSCLC, bladder cancer, & MSI-H cohorts
Presenter: Henry Conter
Session: Poster Display session 3
Resources:
Abstract
3012 - Excellent CBR and Prolonged PFS in Non-Squamous NSCLC with Oral CA-170, an Inhibitor of VISTA and PD-L1
Presenter: Vivek Radhakrishnan
Session: Poster Display session 3
Resources:
Abstract
2536 - Phase Ib/II trial of TG4001 (Tipapkinogene sovacivec), a therapeutic HPV-vaccine, and Avelumab in patients with recurrent/metastatic (R/M) HPV-16+ cancers
Presenter: Christophe Le Tourneau
Session: Poster Display session 3
Resources:
Abstract
1845 - Induction of tumor-infiltrating functional CD8 positive cells and PD-L1 expression in esophageal cancer by S-588410
Presenter: Takashi Kojima
Session: Poster Display session 3
Resources:
Abstract