interesting article in JAMA

[RCOG2000]

Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer

Kim N. Chi, M.D., Neeraj Agarwal, M.D., Anders Bjartell, M.D., Byung Ha Chung, M.D., Andrea J. Pereira de Santana Gomes, M.D., Robert Given, M.D., Álvaro Juárez Soto, M.D., Axel S. Merseburger, M.D., Mustafa Özgüroğlu, M.D., Hirotsugu Uemura, M.D., Dingwei Ye, M.D., Kris Deprince, M.D., et al., for the TITAN Investigators*

Abstract

BACKGROUND

Apalutamide is an inhibitor of the ligand-binding domain of the androgen receptor. Whether the addition of apalutamide to androgen-deprivation therapy (ADT) would prolong radiographic progression–free survival and overall survival as compared with placebo plus ADT among patients with metastatic, castration-sensitive prostate cancer has not been determined.

METHODS

In this double-blind, phase 3 trial, we randomly assigned patients with metastatic, castration-sensitive prostate cancer to receive apalutamide (240 mg per day) or placebo, added to ADT. Previous treatment for localized disease and previous docetaxel therapy were allowed. The primary end points were radiographic progression–free survival and overall survival.

RESULTS

A total of 525 patients were assigned to receive apalutamide plus ADT and 527 to receive placebo plus ADT. The median age was 68 years. A total of 16.4% of the patients had undergone 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. At the first interim analysis, with a median of 22.7 months of follow-up, the percentage of patients with radiographic progression–free survival at 24 months was 68.2% in the apalutamide group and 47.5% in the placebo group (hazard ratio for radiographic progression or death, 0.48; 95% confidence interval [CI], 0.39 to 0.60; P<0.001). Overall survival at 24 months was also greater with apalutamide than with placebo (82.4% in the apalutamide group vs. 73.5% in the placebo group; hazard ratio for death, 0.67; 95% CI, 0.51 to 0.89; P=0.005). The frequency of grade 3 or 4 adverse events was 42.2% in the apalutamide group and 40.8% in the placebo group; rash was more common in the apalutamide group.

CONCLUSIONS

In this trial involving patients with metastatic, castration-sensitive prostate cancer, overall survival and radiographic progression–free survival were significantly longer with the addition of apalutamide to ADT than with placebo plus ADT, and the side-effect profile did not differ substantially between the two groups. (Funded by Janssen Research and Development; TITAN ClinicalTrials.gov number, NCT02489318.)

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[jfoesq]

This study is very interesting. But- I think my doctor would say the same thing she said to me about the study that demonstrated the effectiveness of ADT and Zytiga.( I believe the name of the study regarding the Zytiga was Stampede) The study failed to indicate how the patients who received the placebo did on Apalutimide ( or in the Stampede study with Zytiga- how they did on Zytiga) AFTER their ADT failed. In other words, maybe waiting to give the Apalutimide (or Zytiga) AFTER ADT fails is as effective, or perhaps MORE effective than giving it at the same time.

I was on ADT intermittently for about 5 years and during most of that period, I took Zytiga when I received ADT. But- towards the end of those 5 years, my doctor decided to have me take the ADT continuosly, AND to STOP taking the Zytiga. Fortunately, I responded well to ADT, ADT combined with Zytiga, and now again, with only ADT.

I think my doctor plans on considering giving me Zytiga, or Apalutimide or other drugs, when ADT stops working for me and I become mCRPC.

I would appreciate hearing if anyone has any thoughts about this?

I know many of you believe in being aggressive and giving this cancer everything you can, as soon as you can. I also tend to lean towards aggressive treatment and that;s why I went along with my doctor;s suggestion 7 years ago to get my prostate surgically removed, despite it being against the SOC at the time. But- I have great respect for my doctors' knowledge and judgment- so I am following her lead.

[MarkBC in reply to jfoesq]

I was diagnosed a year ago. I did chemo starting last August and am now only doing ADT. My PSA is continuing to decline slowly from 103 at diagnosis to 0.17 last month. My scans show no sign of progression.

Like you, I have an oncologist, a prostate cancer specialist, whom I trust completely. She works very closely with Dr Kim Chi who is the lead author on this paper. Like your doctor, she believes we should hold back on other drugs as long as the ADT is continuing to work. Based on earlier postings here, I discussed apalutimide with her at my last appointment. She said that she would like to wait until there is more evidence. I will bring up this article when I see her again next month. Again, I trust her judgement. It is so important for us to have confidence in our doctors.

[jfoesq in reply to MarkBC]

MarkBC- It's comforting to see another doctor deciding to hold off on other meds, as long as the ADT is working. It seems as though I read so many posts from people who are taking ADT combined with another med (i.e. apalutimide, xtandi......). Perhaps the combined treatments will eventually be proven to be the better way to treat the disease-perhaps not. But- while it remains unknown for now, it is nice to hear of other patients who are being treated the same way I am.

Thx JFOesq

[jfoesq in reply to MarkBC]

BTW- I was treated by Dr. Howard Scger at MSKCC in NYC for approximately 5 years before Dr. Dana Radkoph took over about 2 years ago. You?

[MarkBC in reply to jfoesq]

My oncologist is Dr Joanna Vergidis at the British Columbia Cancer Agency in Canada. The agency is putting a lot of resources into prostate cancer research. A good friend of mine is a scientist at the agency and often sees Dr Vergidis and Dr Chi at major North American cancer conferences so I know they stay current with the latest research. Here is a short 10 min video of a project that the agency is working on.

youtu.be/8DkhSFS0FY4(Not working as expected?)

[RCOG2000 in reply to MarkBC]

What a great discussion and video. Thank you all

George

[Jbooml in reply to MarkBC]

I was a patient of Dr. Chi’s until he let me off his tether as a result of what one might consider spectacular response to ADT and abi....on my final visit I questioned him as to why I need both and why I couldn’t drop the ADT...He flatly told me that Abi doesn’t work well on its own in cases like mine.

Interesting how many citations I see him toplining these studies.

Hope he finds a common remedy for all of us.

[RCOG2000 in reply to Jbooml]

Me too