Docetaxel + Androgen-Deprivation Therapy in Patients With High-Risk PCa & Rising PSA - no mets.

[pjoshea13]

New French study below.

"To assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease."

"This open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007".

So long ago. Well before Zytiga, Xtandi, etc. appeared.

"Patients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year)."

"The primary outcome was PSA progression-free survival (PSA-PFS)."

"At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 ... months in the ADT plus docetaxel arm vs 19.3 ... months in the ADT alone arm ..."

"Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease."

-Patrick

ncbi.nlm.nih.gov/pubmed/307...

JAMA Oncol. 2019 Jan 31. doi: 10.1001/jamaoncol.2018.6607. [Epub ahead of print]

Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy: A Randomized Clinical Trial.

Oudard S1, Latorzeff I2, Caty A3, Miglianico L4, Sevin E5, Hardy-Bessard AC6, Delva R7, Rolland F8, Mouret L9, Priou F10, Beuzeboc P11, Gravis G12, Linassier C13, Gomez P14, Voog E15, Muracciole X16, Abraham C17, Banu E18, Ferrero JM19, Ravaud A20, Krakowski I21, Lagrange JL22, Deplanque G23, Zylberait D24, Bozec L25, Houede N26, Culine S27, Elaidi R28.

Author information

1

Department of Medical Oncology, Hôpital Européen Georges Pompidou, Paris, France.

2

Department of Oncology Radiotherapy, Clinique Pasteur, Toulouse, France.

3

Department of Medical Oncology, Centre Galilée, Hôpital Privé la Louvière, Lille, France.

4

Department of Oncology Radiotherapy, Centre Hospitalier Privé St Grégoire, Rennes, France.

5

Department of Medical Oncology, Centre François Baclesse, Caen, France.

6

Department of Medical Oncology, Hôpital Privé des Côtes d'Armor, Plérin, France.

7

Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France.

8

Department of Medical Oncology, Institut de Cancérologie de l'Ouest, St Herblain, France.

9

Department of Medical Oncology, Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France.

10

Department of Medical Oncology, Centre Hospitalier de Vendée, La Roche sur Yon, France.

11

Department of Medical Oncology, Institut Curie, Paris, France.

12

Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France.

13

Department of Medical Oncology, Centre Hospitalier Bretonneau, Tours, France.

14

Department of Oncology Radiotherapy, Centre Joliot Curie, Rouen, France.

15

Department of Medical Oncology, Clinique Victor Hugo, Institut Inter-régional de Cancérologie, Le Mans, France.

16

Department of Oncology Radiotherapy, Hôpital de la Timone, Marseille, France.

17

Department of Medical Oncology, Centre Hospitalier Versailles André Mignot, Le Chesnay, France.

18

Department of Medical Oncology, Cancer Institute Ion Chiricuta, Cluj-Napoca, Romania.

19

Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France.

20

Department of Medical Oncology, Hôpital St Andre, Bordeaux, France.

21

Department of Medical Oncology, Centre Alexis Vautrin, Vandoeuvre Les Nancy, France.

22

Department of Medical Oncology, Hôpital Henri Mondor, Creteil, France.

23

Department of Medical Oncology, Fondation Hopital St Joseph, Paris, France.

24

Department of Medical Oncology, Centre Hospitalier de Compiegne, Compiegne, France.

25

Department of Medical Oncology, Hôpital Foch, Suresnes, France.

26

Department of Medical Oncology, Institut Bergonie, Bordeaux, France.

27

Department of Medical Oncology, Hôpital St Louis, Paris, France.

28

Association pour la Recherche sur les Thérapeutiques Innovantes en Cancérologie, Paris, France.

Abstract

IMPORTANCE:

Androgen-deprivation therapy (ADT) plus docetaxel is the standard of care in hormone-naive metastatic prostate cancer but is of uncertain benefit in a nonmetastatic, high-risk prostate cancer setting.

OBJECTIVE:

To assess the benefit of ADT plus docetaxel in patients presenting with rising prostate-specific antigen (PSA) levels after primary local therapy and high-risk factors but no evidence of metastatic disease.

DESIGN, SETTING, AND PARTICIPANTS:

This open-label, phase 3, randomized superiority trial comparing ADT plus docetaxel vs ADT alone enrolled patients from 28 centers in France between June 4, 2003, and September 25, 2007; final follow-up was conducted April 12, 2017, and analysis was performed May 2 to July 31, 2017. Patients had undergone primary local therapy for prostate cancer, were experiencing rising PSA levels, and were considered to be at high risk of metastatic disease. Stratification was by prior local therapy and PSA-level doubling time (≤6 vs >6 months), and intention-to-treat analysis was used.

INTERVENTIONS:

Patients were randomly assigned to receive ADT (1 year) plus docetaxel, 70 mg/m2 (every 3 weeks [6 cycles]), or ADT alone (1 year).

MAIN OUTCOMES AND MEASURES:

The primary outcome was PSA progression-free survival (PSA-PFS). Secondary end points were PSA response, radiologic PFS, overall survival, safety, and quality of life.

RESULTS:

Overall, 254 patients were randomized (1:1) to the trial; median age, 64 years in the ADT plus docetaxel arm, 66 years in the ADT alone arm. At a median follow-up of 30.0 months, the median PSA-PFS was 20.3 (95% CI, 19.0-21.6) months in the ADT plus docetaxel arm vs 19.3 (95% CI, 18.2-20.8) months in the ADT alone arm (hazard ratio [HR], 0.85; 95% CI, 0.62-1.16; P = .31). At a median follow-up of 10.5 years, there was no significant between-arm difference in radiologic PFS (HR, 1.03; 95% CI, 0.74-1.43; P = .88). Overall survival data were not mature. The most common grade 3 or 4 hematologic toxic effects in the ADT plus docetaxel arm were neutropenia (60 of 125 patients [48.0%]), febrile neutropenia (10 [8.0%]), and thrombocytopenia (4 [3.0%]). There was no significant between-arm difference in overall quality of life.

CONCLUSIONS AND RELEVANCE:

Compared with ADT alone, combined ADT plus docetaxel therapy with curative intent did not significantly improve PSA-PFS in patients with high-risk prostate cancer and rising PSA levels and no evidence of metastatic disease.

TRIAL REGISTRATION:

French Health Products Safety Agency identifier: 030591; ClinicalTrials.gov identifier: NCT00764166.

PMID: 30703190 DOI: 10.1001/jamaoncol.2018.6607

[GP24]

" but no evidence of metastatic disease." This is the case if you use CT and bone scan. If you get a PSMA PET/CT most of these patients will show lymph node mets or small bone mets.

The conclusion is that this study showed no benefit for ADT+Docetaxel over ADT alone in a recurrence situation. The guidelines allow to do this based on the STAMPEDE trial. I was unsure about this since STAMPEDE included very few patients in a recurrent situation only.

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Bummer.