You are incorrectly assuming that those who started with Lupron only did not later have second line interventions. In fact, most (74+% in STAMPEDE) of the men in the Lupron control group did
have Zytiga or other second line interventions after they became castration resistant. So the proper way to look at it is the studies compared those who started with
Lupron only to those who started with
Lupron plus Zytiga/prednisone. Naturally, few, if any, men had the initial drug(s) only within the median 40-months of follow up, unless they died before a second-line treatment was used. Second-line treatments may have been any of five: Zytiga, Xtandi, Xofigo, Taxotere, and/or Jevtana.
James et al. said...
Among the patients in the control group (i.e., patients who received androgen-deprivation therapy alone) in the STAMPEDE trial who died of prostate cancer, 74% explicitly reported that they had received one or more of these five therapies. Data on second-, third-, and fourth-line treatments are increasingly difficult to collect and thus are underreported, so true rates of exposure to these therapies will be higher than 74%.
The double-blind, placebo-controlled LATITUDE trial produced strikingly similar outcomes with different patterns of care after relapse; this suggests that differing patterns of care after relapse between the STAMPEDE and LATITUDE trials were not important drivers of differences in survival.
Furthermore, among patients with relapsed disease who had not received previous chemotherapy and who received abiraterone in the COU-AA-302 study, the median progression-free survival was approximately 16.5 months, and the median time to treatment failure in the control group of patients with M1 disease in the STAMPEDE trial was approximately 11 months, so the estimated time to abiraterone failure was 27.5 months. In comparison, the median failure- free survival with first-line abiraterone among patients with metastatic disease in the STAMPEDE trial was approximately 54 months.