Abstract 2975
Background
D and E demonstrated to be efficacious in the treatment of mCRPC pts. Due to different antitumor mechanism of action of these agents, it could be postulated that their combination can improve disease control. CHEIRON study tried to demonstrate the candidate efficacy of chemo-hormonal combination D+E versus D in mCRPC first-line.
Methods
Eligibility criteria included mCRPC diagnosis, ECOG PS ≤ 2, adequate renal, hepatic and hematological functions, no prior treatment for mCRPC. Pts were randomized to receive D 75 mg/m2 IV d1 q3w plus prednisone 5 mg PO BID for 8 courses alone or plus E 160 mg PO daily for 24 weeks. Stratification criteria were presence of pain and visceral metastases. The primary endpoint of the study was the rate of pts without disease progression (according to PCWG2) at 6 mos after randomization.
Results
Between 09/2014 and 10/2017, 246 pts (median age 70 years, range 44-88, pain reported by 54 pts, visceral metastases present in 50 pts) were randomized to DE (120) or D (126). The rate of pts without disease progression at 6 mos was significantly higher in DE arm compared to D arm (89.1% vs 72.8%; p = 0.002). Similarly, a higher proportion of DE pts achieved a PSA reduction ≥ 50% compared to the baseline values compared to the D pts (92% vs 69%; p < 0.0001). No differences were observed in terms of objective response rate. Major haematological toxicities consisted of grade 3-4 neutropenia (19 pts DE – 15 pts D); febrile neutropenia was observed in 10 DE pts and in 7 D pts. At a median follow-up of 24 mos, the median progression free survival was 10.1 mos and 9.1 mos in DE and D arm, respectively (p = 0.01). In DE arm the median overall survival was 33.7 mos compared to 29.6 mos of the standard arm (p NS).
Conclusions
The present study was the first phase II randomized trial, which tested the addition of a new generation hormone agent to D compared to D alone. From this data, DE improved the 6-mo disease control with a prolongation of PFS compared to the standard chemotherapy.
Clinical trial identification
NCT02453009.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Astellas.
Disclosure
O. Caffo: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy: AstraZeneca. D. Gasparro: Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Astellas; Speaker Bureau / Expert testimony: Pfizer. R. Iacovelli: Advisory / Consultancy: Astellas; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis. U.F.F. De Giorgi: Advisory / Consultancy: Astellas; Advisory / Consultancy: Bayer; Advisory / Consultancy: BMS; Advisory / Consultancy: Janssen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Sanofi. G. Pappagallo: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy: Genzyme; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self): Pfizer; Honoraria (self): Pierre Fabre; Honoraria (self): Roche. M. Aglietta: Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Travel / Accommodation / Expenses: Merck; Advisory / Consultancy: Novartis; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): PharmaMar; Travel / Accommodation / Expenses: Tesaro. All other authors have declared no conflicts of interest.
Resources from the same session
5105 - Fresh blood Immune cell monitoring in patients treated with nivolumab in the GETUG-AFU26 NIVOREN study: association with toxicity and treatment outcome
Presenter: Aude DESNOYER
Session: Poster Display session 3
Resources:
Abstract
1877 - Advanced clear-cell renal cell carcinoma (accRCC): association of microRNAs (miRNAs) with molecular subtypes, mRNA targets and outcome.
Presenter: Annelies Verbiest
Session: Poster Display session 3
Resources:
Abstract
5543 - Prior tyrosine kinase inhibitors (TKI) and antibiotics (ATB) use are associated with distinct gut microbiota ‘guilds’ in renal cell carcinoma (RCC) patients
Presenter: Valerio Iebba
Session: Poster Display session 3
Resources:
Abstract
2689 - mTOR mutations are not associated with shorter PFS and OS in patients treated with mTOR inhibitors
Presenter: Cristina Suarez Rodriguez
Session: Poster Display session 3
Resources:
Abstract
3069 - Efficacy of immune checkpoint inhibitors (ICI) and genomic alterations by body mass index (BMI) in Advanced Renal Cell Carcinoma (RCC)
Presenter: Aly-Khan Lalani
Session: Poster Display session 3
Resources:
Abstract
5089 - Finding the Right Biomarker for Renal Cell Carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response.
Presenter: Lorena Incorvaia
Session: Poster Display session 3
Resources:
Abstract
2594 - Algorithms derived from quantitative pathology can be a gatekeeper in patient selection for clinical trials in localised clear cell renal cell carcinoma (ccRCC)
Presenter: In Hwa Um
Session: Poster Display session 3
Resources:
Abstract
2566 - High baseline blood volume is an independent favorable prognostic factor for overall and progression-free survival in patients with metastatic renal cell carcinoma
Presenter: Aska Drljevic-nielsen
Session: Poster Display session 3
Resources:
Abstract
2675 - Impact of estimand selection on adjuvant treatment outcomes in renal cell carcinoma (RCC)
Presenter: Daniel George
Session: Poster Display session 3
Resources:
Abstract
1541 - TERT gene fusions characterize a subset of metastatic Leydig cell tumors
Presenter: Bozo Kruslin
Session: Poster Display session 3
Resources:
Abstract