ADT with/out Zometa

[pjoshea13]

New Japanese Phase III study below.

"To examine the antitumor activity of zoledronic acid {Zometa} combined with androgen deprivation therapy (ADT) for {227} men with treatment-naive prostate cancer and bone metastasis."

"Median {times to treatment failure} were 12.4 and 9.7 months for the {ADT+Zometa} and {ADT} groups, respectively (HR 0.75 ...)."

"For men with baseline prostate-specific antigen levels <200 ng/mL, median {times to treatment failure} were 23.7 and 9.8 months for the {ADT+Zometa} and {ADT} groups, respectively (HR 0.58 ...)."

"Median {times to the first skeletal-related event} were 64.7 and 45.9 months for the {ADT+Zometa} and {ADT} groups, respectively (HR 0.58 ...)."

"{Overall survival} was similar between the groups."

I'm not a fan of bisphosphonates, but CRPC was delayed significantly in a subset of men.

The median time to treatment failure of <10 months in the ADT-only arm seems very low.

-Patrick

ncbi.nlm.nih.gov/pubmed/276...

Int J Clin Oncol. 2016 Sep 10. [Epub ahead of print]

A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial.

Kamba T1, Kamoto T2, Maruo S3, Kikuchi T3, Shimizu Y1, Namiki S4, Fujimoto K5, Kawanishi H6, Sato F7, Narita S8, Satoh T9, Saito H10, Sugimoto M11, Teishima J12, Masumori N13, Egawa S14, Sakai H15, Okada Y16, Terachi T17, Ogawa O18; ZAPCA Study Group.

Author information

1Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan.

2Department of Urology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki, 889-1692, Japan.

3Translational Research Informatics Center, 1-5-4 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.

4Department of Urology, Osaki Citizen Hospital, 3-8-1 Furukawa-Honami, Osaki, 989-6183, Japan.

5Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8522, Japan.

6Department of Urology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka, 543-8555, Japan.

7Department of Urology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hazama-cho, Yufu, Oita, 879-5593, Japan.

8Department of Urology, Graduate School of Medicine, Akita University, 1-1-1 Hondo, Akita, 010-8543, Japan.

9Department of Urology, School of Medicine, Kitasato University, 1-15-1 Kitasato, Minami-ku, Sagamihara, 252-0374, Japan.

10Department of Urology, Graduate School of Medicine, Tohoku University, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

11Department of Urology, School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.

12Department of Urology, Institute of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

13Department of Urology, School of Medicine, Sapporo Medical University, S1 W16, Chuo-ku, Sapporo, 060-8543, Japan.

14Department of Urology, School of Medicine, The Jikei University, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan.

15Department of Urology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

16Department of Urology, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu, 520-2192, Japan.

17Department of Urology, School of Medicine, Tokai University, 143 Shimokasuya, Isehara, 259-1193, Japan.

18Department of Urology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan. [e-mail].

Abstract

OBJECTIVE:

To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis.

METHODS:

We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazards model. Median follow-up duration was 41.5 months.

RESULTS:

Median TTTFs were 12.4 and 9.7 months for the CZ and CAB groups, respectively (HR 0.75; 95 % CI 0.57-1.00; p = 0.051). For men with baseline prostate-specific antigen levels <200 ng/mL, median TTTFs were 23.7 and 9.8 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.35-0.93; p = 0.023). Median TTfSREs were 64.7 and 45.9 months for the CZ and CAB groups, respectively (HR 0.58; 95 % CI 0.38-0.88; p = 0.009). OS was similar between the groups.

CONCLUSIONS:

This study failed to demonstrate that combined use of ZA and ADT significantly prolonged TTTF in men with treatment-naive prostate cancer and bone metastasis. However, it generates a new hypothesis that the combined therapy could delay the development of castration resistance in a subgroup of patients with low baseline prostate-specific antigen values <200 ng/mL. The treatment also significantly prolonged TTfSRE but did not affect OS.

KEYWORDS:

Antitumor activity; Castration sensitive; Primary androgen deprivation; Prostate cancer; Zoledronic acid

PMID: 27614621 DOI: 10.1007/s10147-016-1037-2

[PubMed - as supplied by publisher

[Dan59]

Patrick, I am wondering if you could give an anylisis of this in plain terms, to me it means thant men who had zometa with adt did better and the ones with bpsa < 200 did much better indicating zometa has a anticancer effect as we all thought before.

[pjoshea13 in reply to Dan59]

Dan,

That's correct. Zometa extended the effectiveness of ADT. Very much so when baseline PSA levels were <200 ng/mL.

The paper notes, however, that:

"{Overall survival} was similar between the groups."

It's odd, since the lower PSA group had almost 14 months more before ADT failure.

...

In a paper from the STAMPEDE trial published this year:

"Zoledronic acid {ZA} showed no evidence of survival improvement and should not be part of standard of care for this population."

ncbi.nlm.nih.gov/pmc/articl...

"Our results for zoledronic acid show no convincing evidence of worthwhile benefit either on failure-free or overall survival. These results are congruent with emerging results from other trials in men starting long-term hormone therapy."

Note: "SOC" = "standard of care", i.e. ADT.

"There were 761 events in patients on SOC-only; median failure-free survival 20 months; 5-year failure-free survival 28%. With 374 events there was no evidence of improvement in failure-free survival with SOC + ZA ...; median failure-free survival was 22 months and 5-year failure-free survival was 31%."

The numbers actually show 2 extra months before ADT failure (22 versus 20), & 3% more cases surviving being on ADT for more than 5 years (31% versus 28%). But nothing dramatic.

-Patrick

[Dan59 in reply to pjoshea13]

Patrick, thank You for your research, I did have zometa with early adt for almost 6 or 7 years, I guess when I get healed up I may do some more zometa

[JoelT]

This study did not factor in the many possible side effects of ZA, some which are very significant. These side effects, in my opinion, far out weight any positive for men in the subgroup of having a delay in the development of castrate resistance.

Joel