Meta-analysis of data on ADT + docetaxel as first-line therapy for metastatic prostate cancer

Another paper at the European Cancer Congress this year has given us meta-analyses of data from studies of docetaxel chemotherapy + standard of care (i.e., some form of androgen deprivation therapy or ADT) in treatment of men newly diagnosed with metastatic (M1) and advanced but non-metastatic (M0) prostate cancer.

The first meta-analysis in the paper by Vale et al. (search for “Rydzewska” in the author names on the abstract search page) involved patients with metastatic (M1) disease from five randomized trials including men treated in the CHAARTED trial, the GETUG AFU-15 trial, and the STAMPEDE trial. The results of this meta-analysis of men with M1 disease showed that:

  • At 4 years of follow-up, adding docetaxel chemotherapy to ADT
    • Improved overall survival by 11 percent (from 40 to 51 percent) among a total of 2,262 patients, 926 of whom died within the 4-year follow-up period (hazard ratio [HR] = 0.73, p < 0.0001)
    • Reduced treatment failure rates by 16 percent (from 80 to 64 percent) among the same 2,262 patients, 1,658 of whom exhibited treatment failure within the 4-year follow-up period (HR = 0.63, p < 0.0001).

The second meta-analysis involved patients with non-metastatic (M0) disease and included men from the CHAARTED trial, the GETUG AFU-15 trial, the STAMPEDE trial, and the TAX-3501 trial. The results of this meta-analysis showed that

  • At 4 years of follow-up, adding docetaxel chemotherapy to ADT
    • Showed no no clear overall survival benefit among a total of 1,665 patients, 286 of whom died within the 4-year follow-up period (HR = 0.86, p = 0.22)
    • Reduced treatment failure rates by 8 percent (from 30 to 22 percent) among 1,893 patients, 690 of whom exhibited treatment failure within the 4-year follow-up period (HR = 0.69, p < 0.0001).

We understand that this research group is planning an international individual participant data meta-analysis which should be able, reliably, to characterize the impact of the addition of docetaxel to ADT on overall survival and on prostate cancer-specific survival and to determine whether the effects vary by patient or tumor characteristics.

Other meta-analyses presented by the research team involved the addition of bisphosphonates like zoledronic acid or clodronate to ADT in men with M0 and M1 disease. While there appeared to be a small potential effect on overall survival in men with M1 disease, this was driven entirely by the addition of clodronate and was not observed among men being given zoledronic acid.

The authors conclude that there was “substantial and reliable evidence for adding docetaxel to ADT for men with M1 disease.” However, additional trials with longer-term follow-up would be needed to demonstrate a benefit in men with M0 disease.

Additional information about these meta-analyses can be found in an article by Caroline Helwick in The ASCO Post, which also offers expert commentary on these meta-analyses and their implications by Ronald de Wit. Interestingly, Dr. de Wit takes the position that

My conclusion is that men presenting with metastatic prostate cancer who are fit to receive chemotherapy should be offered six cycles of docetaxel plus androgen-deprivation therapy. There is no distinction between high- and low-volume disease. Any metastatic disease by TNM criteria will do.

This is a more aggressive interpretation of the available data than that currently being taken by the majority of U.S.-based experts on the management of metastatic prostate cancer.

One Response

  1. Encouraging, but Distinction from CHAARTED Results Is not Addressed in the Studies (per links)

    A key distinction in the CHAARTED results was that the chemo + ADT combo worked when men had more disease – beyond just metastases in the spine and pelvis, but did not have an advantage when metastases did not extend beyond the spine and pelvis. At least that is my understanding. The meta-analyses do not address this distinction; indeed one author indicates that the volume of disease does not matter, a sharp contrast to the original lesson from CHAARTED! In the Vale/Rydzewska abstract, it appears the only distinction was between metastatic and non-metastatic patients rather than also between kinds of metastatic patients, as above re spine and pelvis or beyond.

    It would be interesting to see if a meta analysis could be done using the same original distinction in CHAARTED.

    My reading of the linked material leads me to think the authors are not distinguishing between the patients who have mets beyond just the spine and pelvis and the rest; it seems these authors are using a “one size fits all” approach. In view of the CHAARTED results, have they really got a good case for one-size-fits-all metastatic patients? I’m unconvinced so far but am glad they are trying the analysis.

    Regarding the second meta analysis, I am more interested in this issue than perhaps others of us as I fell within the scope of enthusiasm by the current authors based on my case characteristics back in late 1999/early 2000: non-metastatic, apparently, but quite advanced in other respects. Again, I’m unconvinced so far but am glad they are trying the analysis.

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