LATITUDE - Zytiga & ADT - NEJM Paper

[pjoshea13]

Further to my "LATITUDE - Zytiga & ADT" post, here is the study paper.

"The two primary end points were overall survival and radiographic progression-free survival."

"After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62"

"The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47"

-Patrick

ncbi.nlm.nih.gov/pubmed/285...

N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1704174. [Epub ahead of print]

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer.

Fizazi K1, Tran N1, Fein L1, Matsubara N1, Rodriguez-Antolin A1, Alekseev BY1, Özgüroğlu M1, Ye D1, Feyerabend S1, Protheroe A1, De Porre P1, Kheoh T1, Park YC1, Todd MB1, Chi KN1; LATITUDE Investigators.

Author information

1

From Gustave Roussy, University of Paris Sud, Villejuif, France (K.F.); Janssen Research and Development, Los Angeles (N.T.), Beerse, Belgium (P.D.P.), San Diego, CA (T.K.), and Raritan, NJ (Y.C.P.); Instituto de Oncologia de Rosário, Rosário, Argentina (L.F.); National Cancer Center Hospital East, Chiba, Japan (N.M.); 12 de Octubre University Hospital, Madrid (A.R.-A.); P.A. Hertsen Moscow Cancer Research Institute, Moscow (B.Y.A.); Cerrahpaşa Medical Faculty, Istanbul University, Istanbul, Turkey (M.Ö.); Fudan University Shanghai Cancer Center, Shanghai, China (D.Y.); Studienpraxis Urologie, Nürtingen, Germany (S.F.); Oxford University Hospitals Foundation NHS Trust, Oxford, United Kingdom (A.P.); Janssen Global Services, Raritan, NJ (M.B.T.); and BC Cancer Agency, Vancouver, Canada (K.N.C.).

Abstract

Background Abiraterone acetate, a drug that blocks endogenous androgen synthesis, plus prednisone is indicated for metastatic castration-resistant prostate cancer. We evaluated the clinical benefit of abiraterone acetate plus prednisone with androgen-deprivation therapy in patients with newly diagnosed, metastatic, castration-sensitive prostate cancer. Methods In this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 1199 patients to receive either androgen-deprivation therapy plus abiraterone acetate (1000 mg daily, given once daily as four 250-mg tablets) plus prednisone (5 mg daily) (the abiraterone group) or androgen-deprivation therapy plus dual placebos (the placebo group). The two primary end points were overall survival and radiographic progression-free survival. Results After a median follow-up of 30.4 months at a planned interim analysis (after 406 patients had died), the median overall survival was significantly longer in the abiraterone group than in the placebo group (not reached vs. 34.7 months) (hazard ratio for death, 0.62; 95% confidence interval [CI], 0.51 to 0.76; P<0.001). The median length of radiographic progression-free survival was 33.0 months in the abiraterone group and 14.8 months in the placebo group (hazard ratio for disease progression or death, 0.47; 95% CI, 0.39 to 0.55; P<0.001). Significantly better outcomes in all secondary end points were observed in the abiraterone group, including the time until pain progression, next subsequent therapy for prostate cancer, initiation of chemotherapy, and prostate-specific antigen progression (P<0.001 for all comparisons), along with next symptomatic skeletal events (P=0.009). These findings led to the unanimous recommendation by the independent data and safety monitoring committee that the trial be unblinded and crossover be allowed for patients in the placebo group to receive abiraterone. Rates of grade 3 hypertension and hypokalemia were higher in the abiraterone group. Conclusions The addition of abiraterone acetate and prednisone to androgen-deprivation therapy significantly increased overall survival and radiographic progression-free survival in men with newly diagnosed, metastatic, castration-sensitive prostate cancer. (Funded by Janssen Research and Development; LATITUDE ClinicalTrials.gov number, NCT01715285 .).

PMID: 28578607 DOI: 10.1056/NEJMoa1704174

[Blair77]

We discussed this today with my husbands oncologist. He said he would know more after the paper was actually presented not just the abstract.

[pjoshea13 in reply to Blair77]

Blair,

I post Abstracts because they are free. When an Abstract is available, so is the full text. Anyone can purchase the full text from the journal.

-Patrick

[Blair77 in reply to pjoshea13]

Patrick,

Yes, thanks for posting!

[TommyTV]

I've been on th Stampede trial in the U.K., arm G which is Abiraterone plus prednisone plus Zoladex for ADT.

PSA at start >600, 7 major bone mets, Gleason 7, PSA dropped to immeasurable within 4 weeks, and has stayed there for the last 5.5 years.

Definitely worked wonders for me.

[Dr_WHO]

Will be seeing my medical oncologist about this on Monday.

[Beermaker]

I find this very interesting, and possible quite relevant. I am 5.5 years into the journey, I currently have a PSA that is undetectable @ <0.1 (Quest diagnostics) but have 4 lymph node metastases that developed quite quickly during a trial vacation from ADT. The only PCa treatment I take is Trelstar ADT. My medical oco is a "one step at a time" doc, Thoughts on this?

~ Marshall

[pjoshea13 in reply to Beermaker]

Marshall,

I can see why some are attracted to "one step at a time". In the days of very few options, or even today, there might be comfort in having something in reserve. But with mean-time-to-failure [MTF] measured in months, rather than years, it's not a viable approach for younger men with serious cancer.

Dr. Myers says that no other form of cancer has ever been controlled by monotherapy - several drugs are required. In effect, he argues that a combo will have a MTF that far exceeds the sum of the individual MTFs.

He talks about that in the early part of this talk:

grandroundsinurology.com/du...

-Patrick