Abstract 3228
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
Characteristics | 3rd LPD n = 602 | Missings n(%) |
---|---|---|
Age (years) a | 71.1 ± 7.4 | 0 |
Time from CRPC to start treatment (months) b | 24.6 (16.7-34.1) | 0 |
Time from castration to CRPC (months) b | 13.0 (7.8-23.2) | 0 |
ECOG PS | 132 (21.9) | |
- 0 | 103 (17.1) | |
- 1 | 278 (46.2) | |
->1 | 89 (14.8) | |
Opioid use c | 153 (25.4) | 66 (11.0) |
Symptomatic c | 466 (77.4) | 50 (8.3) |
Metastatic site c | ||
- Bone | 536 (89.0) | 46 (7.6) |
- Visceral | 102 (16.9) | 260 (43.1) |
- Lymphnode | 263 (43.7) | 208 (43.5) |
Hemoglobin (mmol/l) a | 7.2 ± 1.1 | 54 (9.0) |
Platelets (109/L) b | 253 (199.0-320.7) | 62 (10.3) |
Prostate-specific antigen (ug/l) b | 170 (60.9-470.5) | 37 (6.1) |
Alkaline phosphatase (U/l) b | 153 (90.5-301.0) | 61 (10.1) |
Lactate dehydrogenase (U/l) b | 261 (207.5-383.0) | 144 (23.9) |
3rd line LPD treatment c | ||
- Abiraterone acetate | 137 (22.8) | 0 |
- Enzalutamide | 129 (21.4) | 0 |
- Docetaxel | 45 (7.5) | 0 |
- Cabazitaxel | 213 (35.4) | 0 |
- Radium-223-chloride | 78 (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.
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