Treatment outcomes of 3rd treatment in a real-world metastatic castration resistant prostate cancer (mCRPC) population: results from the Dutch CAPR...

Date 30 September 2019
Event ESMO 2019 Congress
Session Poster Display session 3
Topics Prostate Cancer
Presenter Jessica Notohardjo
Citation Annals of Oncology (2019) 30 (suppl_5): v325-v355. 10.1093/annonc/mdz248
Authors J.C..L. Notohardjo1, M.C.P. Kuppen2, H.M. Westgeest3, A.J.M. van den Eertwegh1, J. Van Moorselaar4, N. Mehra5, J..L. Coenen6, I. van Oort7, A.C.M. van den Bergh8, K.K.H. Aben9, D.M. Somford10, R. de Wit11, A.M. Bergman12, L. Lavalaye13, C. Uyl-de Groot14, W.R. Gerritsen15
  • 1Department Of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit, 1081 HV - Amsterdam/NL
  • 2Institute For Medical Technology Assessment, Erasmus School of Health Policy and Management, 3062 PA - Rotterdam/NL
  • 3Department Of Internal Medicine, Amphia Hospital, 4819 EV - Breda/NL
  • 4Department Of Urology, Amsterdam UMC, Vrije Universiteit, 1081 HV - Amsterdam/NL
  • 5Department Of Medical Oncology, Radboud University Medical Center, 6525 GA - Nijmegen/NL
  • 6Department Of Medical Oncology, Isala, 8025 AB - Zwolle/NL
  • 7Department Of Urology, Radboud University Medical Center, 6525 GA - Nijmegen/NL
  • 8Department Of Radiation Oncology, University Medical Center Groningen, University of Groningen, 9713 GZ - Groningen/NL
  • 9Department Of Research, Netherlands Comprehensive Cancer Organization, 6533AA - Nijmegen/NL
  • 10Department Of Urology, Canisius Wilhemina Ziekenhuis, 6532 SZ - Nijmegen/NL
  • 11Department Of Medical Oncology, Erasmus MC Daniel den Hoed Cancer Center, 3075EA - Rotterdam/NL
  • 12Division Of Internal Medicine (mod) And Oncogenomics, The Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, 1066 CX - Amsterdam/NL
  • 13Department Of Nuclear Medicine, St Antonius Hospital, 3435CM - Nieuwegein/NL
  • 14Institute Of Health Policy & Management, Institute for Medical Technology Assessment, Erasmus University, 3062 PA - Rotterdam/NL
  • 15Department Of Medical Oncology, Radboud University Medical Center, 6525 XZ - Nijmegen/NL

Abstract

Background

Data on outcomes of a 3rd line life prolonging drug (LPD) in patients with metastatic castration resistant prostate cancer (mCRPC) is lacking. Aim of this study was to evaluate outcomes of a 3rd LPD in a real-world cohort of mCRPC patients.

Methods

mCRPC patients with a 3rd LPD before July 1st 2017 were retrospectively identified from the Dutch Castration-resistant Prostate Cancer Registry (CAPRI) and followed to December 31st 2017. Outcomes were overall survival (OS), treatment duration (TD) and PSA response. The association of potential risk factors with death was tested by Cox proportional-hazard models after multiple imputation of missing baseline characteristics.

Results

We identified 602 patients treated with a 3rd LPD. Baseline characteristics are listed in the table. Median OS was 7.8 mo (IQR 4.4-14.0), median TD was 3.2 mo (IQR 1.9-4.7) and PSA response (≥ 50% decline) was observed in 131 patients (22%). ECOG PS of 1 and >1 (HR 1.48, p < 0.01 and HR 1.75, p < 0.01, respectively), opioid use (HR 1.51, p < 0.01), symptoms (HR 1.50, p = 0.04), visceral metastases (HR 2.11, p < 0.01), PSA ≥170 ug/l (HR 1.32, p < 0.01), alkaline phosphatase ≥150 U/l (HR 1.66, p < 0.01) and time from CRPC to start 3rd LPD <24 mo (HR 1.56, p < 0.01) were related to shorter survival in multivariable analysis. Patients were categorized into low (0-1 point, n = 81), low-intermediate (2-3 points, n = 262), high-intermediate (4-5 points, n = 208) and high risk (6-7 points, n = 51) prognosis groups based on the number of prognostic factors and their regressions coefficients. These groups had a median OS of 20.4, 11.0, 6.6 and 3.9 mo, with a median TD of 4.6, 3.4, 2.6 and 1.9 mo, respectively (p < 0.01).Table:

865P Baseline characteristics at start of a 3rd line line prolonging drug (LPD) treatment

Characteristics3rd LPD n = 602Missings n(%)
Age (years) a71.1 ± 7.40
Time from CRPC to start treatment (months) b24.6 (16.7-34.1)0
Time from castration to CRPC (months) b13.0 (7.8-23.2)0
ECOG PS132 (21.9)
- 0103 (17.1)
- 1278 (46.2)
->189 (14.8)
Opioid use c153 (25.4)66 (11.0)
Symptomatic c466 (77.4)50 (8.3)
Metastatic site c
- Bone536 (89.0)46 (7.6)
- Visceral102 (16.9)260 (43.1)
- Lymphnode263 (43.7)208 (43.5)
Hemoglobin (mmol/l) a7.2 ± 1.154 (9.0)
Platelets (109/L) b253 (199.0-320.7)62 (10.3)
Prostate-specific antigen (ug/l) b170 (60.9-470.5)37 (6.1)
Alkaline phosphatase (U/l) b153 (90.5-301.0)61 (10.1)
Lactate dehydrogenase (U/l) b261 (207.5-383.0)144 (23.9)
3rd line LPD treatment c
- Abiraterone acetate137 (22.8)0
- Enzalutamide129 (21.4)0
- Docetaxel45 (7.5)0
- Cabazitaxel213 (35.4)0
- Radium-223-chloride78 (13.0)0

Note: Data are defined as amean ± SD, bmedian (IQR) or cnumber of patients (%). Abbreviations: CRPC; Castration-resistant prostate Cancer, ECOG PS;

Eastern Cooperative Oncology Group Performance Score.

Conclusions

Our results show that the efficacy of a 3rd LPD in mCRPC patients was limited compared to pivotal trials of 1st and 2nd line. We used a simple prognostic model to identify mCRPC patients that can benefit from a 3rd LPD.

Clinical trial identification

NL3440 (NTR3591).

Editorial acknowledgement

Legal entity responsible for the study

Institute for Medical Technology Assessment, Erasmus University Rotterdam.

Funding

Sanofi-Aventis Netherlands B.V., Janssen-Cilag B.V., Astellas Pharma B.V., Bayer B.V.

Disclosure

M.C.P. Kuppen: Travel / Accommodation / Expenses: Ipsen. H.M. Westgeest: Travel / Accommodation / Expenses: Ipsen; Honoraria (self): Roche. A.J.M. van den Eertwegh: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Oncology; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Ipsen; Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck. J. Van Moorselaar: Honoraria (institution), Advisory / Consultancy: Amgen; Honoraria (institution), Advisory / Consultancy: Astellas; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Bayer; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution), Advisory / Consultancy: Sanofi-Genzyme. N. Mehra: Research grant / Funding (institution): Astellas; Honoraria (self), Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Sanofi; Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): Merck; Honoraria (self): Bayer; Honoraria (self): BMS; Honoraria (self): MSD. J.L. Coenen: Advisory / Consultancy: Sanofi. I. van Oort: Advisory / Consultancy, Research grant / Funding (institution): Astellas; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Mdx Health; Advisory / Consultancy: Astellas. D.M. Somford: Research grant / Funding (institution): Astellas. R. de Wit: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Honoraria (institution), Advisory / Consultancy: Merck; Honoraria (institution), Advisory / Consultancy: Sharp&Dohme; Advisory / Consultancy: Roche/ Genentech; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Clivis; Travel / Accommodation / Expenses: Lilly. A.M. Bergman: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bayer; Speaker Bureau / Expert testimony: Janssen. C. Uyl-de Groot: Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Astellas; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genzyme; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Glycostem Therapeutics; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Merck. W.R. Gerritsen: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Speaker Bureau / Expert testimony: Bavarian Nordic; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bristol-Myers Squibb; Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen-Cilag; Advisory / Consultancy: Amgen; Advisory / Consultancy: Merck; Advisory / Consultancy: Morphosys; Advisory / Consultancy: Sanofi; Advisory / Consultancy, Ad hoc Consultancy: Aglaia Biomedical Ventures; Advisory / Consultancy, Ad hoc Consultancy: Psioxus Therapeutics; Advisory / Consultancy: Curvevac; Advisory / Consultancy: Dendreon. All other authors have declared no conflicts of interest.