Survival is about more than testosterone suppression


CHICAGO — Men with metastatic hormone sensitive prostate cancer need more than testosterone suppression, but exactly what drug should comprise that “more” is still being adjudicated.

On the flip side, at least two candidates for that “more” position demonstrated clear benefits: 80% of men treated with enzalutamide were alive after 3 years, as were 82.4% of men treated with apalutamide at 2 years. In both cases, the results were significantly better than controls.

The enzalutamide findings emerged from the ENZAMET trial and the apalutamide from the TITAN trial, both of which were presented here at the American Society of Clinical Oncology meeting.

Asked to sort out the findings, Robert Dreicer, MD, of the University of Virginia, put it this way: “It is clear that almost every patient [with metastatic hormone-sensitive prostate cancer] needs ADT plus an additional therapy — a next androgen-targeted therapy. There are evolving data that may provide insight on one or the other choice.”

Dreicer added that neither trial should be considered definitive, although ENZAMET “tells us you can give enzalutamide with docetaxel.” Dreicer was not involved in either study.

ENZAMET recruited 1,125 men and randomized them to enzalutamide (n=596) or bicalutamide, nilutamide, or flutamide with or without docetaxel.

ENZAMET investigator Christopher Sweeney, MBBS, of Dana-Farber Cancer Center in Boston, said that men with low volume disease did benefit from enzalutamide, but the survival benefit was not significant.

Among the findings at 3 years:

  • 71% of men with high volume disease taking enzalutamide were alive versus 64% of controls
  • Among men who received enzalutamide without docetaxel, 83% were alive versus 70% in the control group.
  • 64% of men taking enzalutamide were still on the study drug at 3 years versus 36% of controls.

In the TITAN trial, the overall survival percentage at 24 months was 82.4% in the apalutamide group and 73.5% in the placebo group (hazard ratio for death, 0.67; 95% CI, 0.51-0.89; P = 0.005). TITAN trial lead author Kim N. Chi, MD, of BC Cancer and Vancouver Prostate Centre, Vancouver, BC, Canada, said “there was a 33% lower risk of death in the apalutamide group.”

The median age of men in TITAN was 68, 16.4% of the patients had under-gone prostatectomy or received radiotherapy for localized disease, and 10.7% had received previous docetaxel therapy; 62.7% had high-volume disease, and 37.3% had low-volume disease.

Chi concluded, “apalutamide plus ADT resulted in significantly longer overall survival and radiographic progression–free survival than placebo plus ADT. The safety profile did not differ notably between the two groups, and health-related quality of life was preserved during apalutamide.”

Both TITAN and ENZAMET were simultaneously published in The New England Journal of Medicine.

 

Disclosure:

Sweeney disclosed consulting or advisory role with Sanofi, Janssen Biotech, Astellas Pharma, Bayer, Genentech/Roche, AstraZeneca, Pfizer, Amgen, Patents, Royalties, Other Intellectual Property for Leuchemix, Parthenolide, Dimethylaminoparthenolide. Exelixis: Abiraterone plus cabozantinib combination, Stock and Other Ownership Interests in Leuchemix, Research Funding from Dendreon, Research Funding (Institutional) from Janssen Biotech, Astellas Pharma, Sanofi, Bayer and Sotio.

Davis disclosed that he was director and chair of ANZUP Cancer Trials Group, the sponsor of the ENZAMET trial (unremunerated). All honoraria for work with industry are invoiced by and paid directly to ANZUP Cancer Trials Group, with no pass-through payments of any sort.

TITAN was supported by Janssen Research and Development. Funding for editorial assistance was provided by Janssen Global Services.

Chi reported grants from Janssen, during the conduct of the study; grants and personal fees from Janssen, grants and personal fees from Astellas, grants and personal fees from Essa, grants and personal fees from Sanofi, grants and personal fees from Bayer, grants and personal fees from Roche, grants and personal fees from AstraZeneca, outside the submitted work.

 

Source:

Chi, KN, et al “Apalutamide for metastatic, castration-sensitive prostate cancer” N Engl J Med 2019; Published online May 31 DOI: 10.1056/NEJMoa1903307.

“Overall survival (OS) results of a phase III randomized trial of standard-of-care therapy with or without enzalutamide for metastatic hormone-sensitive prostate cancer (mHSPC): ENZAMET (ANZUP 1304), an ANZUP-led international cooperative group trial” ASCO 2019; Abstract LBA2.

 

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