Zytiga: "Phase II pilot study of the prednisone to dexamethasone switch ..."

[pjoshea13]

New paper below. The SWITCH study (Spain / UK).

"Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid."

"Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%."

-Patrick

ncbi.nlm.nih.gov/pubmed/301...

Br J Cancer. 2018 Aug 21. doi: 10.1038/s41416-018-0123-9. [Epub ahead of print]

Phase II pilot study of the prednisone to dexamethasone switch in metastatic castration-resistant prostate cancer (mCRPC) patients with limited progression on abiraterone plus prednisone (SWITCH study).

Romero-Laorden N1,2, Lozano R1,3,4, Jayaram A5,6, López-Campos F1,7, Saez MI4,8, Montesa A4,8, Gutierrez-Pecharoman A2,9, Villatoro R4,10, Herrera B4,11, Correa R4,12, Rosero A1,13, Pacheco MI1,4, Garcés T1,4, Cendón Y1,14, Nombela MP1, Van de Poll F1, Grau G1,4, Rivera L1,4, López PP1, Cruz JJ3, Lorente D15, Attard G5,6, Castro E16,17, Olmos D1,4,8.

Author information

1

Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

2

Medical Oncology Department, Hospital Universitario de La Princesa, Madrid, Spain.

3

Medical Oncology Department, Hospital Universitario de Salamanca, Salamanca, Spain.

4

CNIO-IBIMA Genitourinary Cancer Research Unit, Institute of Biomedical Research in Málaga (IBIMA), Málaga, Spain.

5

Division of Molecular Pathology, Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom.

6

Academic Urology, The Royal Marsden NHS Foundation Trust, London, United Kingdom.

7

Radiation Oncology Department, Hospital Universitario Ramón y Cajal, Madrid, Spain.

8

Medical Oncology Department, Hospitales Universitarios Virgen de la Victoria y Regional de Málaga, Málaga, Spain.

9

Pathology Department, Hospital Universitario de Móstoles, Móstoles, Spain.

10

Medical Oncology Department, Hospital Costa del Sol, Marbella, Spain.

11

Urology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain.

12

Radiation Oncology Department, Hospital Universitario Virgen de la Victoria, Málaga, Spain.

13

Oncology Department, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain.

14

School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain.

15

Medical Oncology Department, Hospital Universitario La Fe, Valencia, Spain.

16

Prostate Cancer Clinical Research Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [e-mail].

17

Medical Oncology Department, Hospital Universitario Quirón, Madrid, Spain. [e-mail].

Abstract

BACKGROUND:

Despite most metastatic castration-resistant prostate cancer (mCRPC) patients benefit from abiraterone acetate plus prednisone 5 mg bid (AA + P), resistance eventually occurs. Long-term use of prednisone has been suggested as one of the mechanisms driving resistance, which may be reversed by switching to another steroid.

METHODS:

SWITCH was a single-arm, open-label, single-stage phase II study. The primary objective was to evaluate the antitumour activity of abiraterone acetate plus dexamethasone 0.5 mg daily (AA + D) in mCRPC patients progressing to AA + P. Clinically stable mCRPC patients who had prostate-specific antigen (PSA) and/or limited radiographic progression after at least 12 weeks on AA + P, were eligible. The primary endpoint was measured as the proportion of patients achieving a PSA decline of  ≥ 30% (PSA30) from baseline after 6 weeks on AA + D. Secondary endpoints included: PSA50 response rate at 12 weeks, time to biochemical and radiological progression, overall survival, safety profile evaluation, benefit from subsequent treatment lines and the identification of biomarkers of response (AR copy number, TMPRSS2-ERG status and PTEN expression).

RESULTS:

Twenty-six patients were enrolled. PSA30 and PSA50 were 46.2% and 34.6%, respectively. Median time to biochemical and radiological progression were 5.3 and 11.8 months, respectively. Two radiological responses were observed. Median overall survival was 20.9 months. Patients with AR gain detected in plasma circulating tumour DNA did not respond to switch, whereas patients with AR normal status benefited the most. No significant toxicities were observed and PSA50 response rate to subsequent taxane was 50%.

CONCLUSIONS:

In selected clinical stable mCRPC patients with limited disease progression on AA + P, a steroid switch from prednisone to dexamethasone can lead to PSA and radiological responses.

PMID: 30131546 DOI: 10.1038/s41416-018-0123-9

[Hidden]

I've discussed with my doctor switching to Dexamethasone if I progressed and he was OK with that. It looks like the study didn't evaluate whether it would beneficial to be on Dexamethasone from the beginning, just switching after progression.

I've just started Zytiga and wondering whether I should ask my doctor about using Dexamethasone now instead of waiting, especially if prednisone speeds up resistance. My doctor seems to prefer Prednisone.

Anyone know if there any disavantage to Dex?

[Hidden]

Great post, thank you.

[Hidden]

Here's a link to more information about this:

ncbi.nlm.nih.gov/pmc/articl...

I just sent an e-mail to my doctor on this subject, waiting for a response. I'll post what he says.

[cesanon]

Patrick, nice article. Thanks.

Do you know the extent to which this is affecting the current practices? Is it starting to inform the practices of docs?

[Rogersw]

I have had a relatively good experience with Dexamethasone in that my PSA was rising up to 19 two years ago so they put me on that along with Prostrap (Lupron) and it has been steady on 7 for 24 months

[rassusukumaran in reply to Rogersw]

You mean you were only on Lupron+ Dax and it lasted for 24 months?

[Rogersw in reply to rassusukumaran]

Still on same meds so that’s now 3 years last psa @6.5 diagnosed 51/2 years ago psa 180

[rassusukumaran in reply to Rogersw]

Well done.

[rassusukumaran]

I am CRPC after 11.5 years on hormone manipulation on all standard protocals. Wish to report that I switched to Dax from Prednisolone after being on Zytiga for nearly 4 months. There was no appreciable effect on PSA numbers. My PSA was 13.7 and rising. After reading a report on this site about the Dax switch, suggested a change to my treating urologist. In one month PSA dropped to 1.4. Am relieved and wondering for how long.

[Peterd110 in reply to rassusukumaran]

How long did the switch to dexamethasone work for you?

[rassusukumaran in reply to Peterd110]

It worked for about 10 months max. Psa slowly climbed to present 16.8

[Peterd110 in reply to rassusukumaran]

Thanks.

I have recently switched. Hope I get that much time from the switch I was at 2.26 before the switch then 1.84 about a week after switching. That was a month ago so we’ll see soon what it is doing.

[scarlino]

I’ve been on clinical trial combining Zytiga, Prednisone and Apalutemide with Lupron for last 18 months. My PSA got to 0.6 and stayed steady for 15 months. It is now increasing 0.6 each month which means this clinical trial is over. Was wondering if you know of any info on going to Zytiga and dexamethasone and Lupron after the last cocktail I was on? They have me slated for an immunotherapy CT, but I would be willing to try this first and see if any improvement.