Zoledronic Acid Update

Gitane · May 2011

http://abstract.asco.org/AbstView_102_83575.html

This is an abstract that will be presented at the 2011 ASCO conference. It's an update after 6 years (68 months) of the ABCSG-12 study. It contains preplanned subgroup analyses. I'll cut and paste what I can below. It states that with a low-estrogen environment ZOL benefit for DFS and OS exists and is highly significant.

Gitane · May 2011

Abstract:Background: Adjuvant zoledronic acid (ZOL) significantly improved disease-free survival (DFS) in premenopausal patients (pts) with endocrine-responsive early breast cancer in ABCSG-12 (Gnant et al. NEJM 2009). The ZOL anticancer effect was confirmed in other prospective trials, such as ZO-FAST and the postmenopausal (> 5 yrs) cohort of AZURE. Long-term follow-up of ABCSG-12 (> 6 yr) now allows pre-planned subgroup analyses that more precisely identify the ZOL benefit, and interactions with pt and tumor characteristics. Methods: Premenopausal pts with early breast cancer (N = 1,803) were randomized to ovarian function suppression with goserelin (3.6 mg q28d) and tamoxifen (TAM; 20 mg/d) or anastrozole (ANA; 1 mg/d) ± ZOL (4 mg q6mo) for 3 yr. Endpoints included DFS and overall survival (OS), both analyzed using log-rank test and Cox models. Preplanned subgroup analyses included subpopulation treatment effect pattern plot (STEPP). Results: At 68 mo median follow-up, ZOL significantly reduced the risk of DFS events by 32% vs no ZOL (HR = 0.68; P = .009); in addition, there was a strong trend toward reduced risk of death (HR = 0.66; P = .08) with ZOL vs no ZOL. Multivariate analyses showed no interaction between ZOL benefit and ANA/TAM or any classic tumor parameter (eg, T, N, grade, ER). However, a strong interaction between ZOL and pt age was demonstrated. Pts > 40 yr of age (n = 1,390) derived significant DFS benefits from ZOL (HR = 0.58; 0.40-0.83; P = .003), whereas there was no apparent benefit in pts < 40 yr of age. ZOL reduced the risk of death by 42% in pts > 40 yr of age (P = .05), with presumed complete ovarian blockade. In several age subgroups > 40 yr, HRs < 0.5 were observed for both DFS and OS. Conclusions: ABCSG-12 long-term follow-up at 68 mo suggests that anticancer benefits of adjuvant ZOL mainly occur in pts with a low-estrogen environment. As in the postmenopausal (> 5 yrs) cohort of AZURE, ZOL leads to highly significant DFS and OS benefits. This suggests that both estrogen deprivation and reduction of bone-turnover–derived growth factors in the bone marrow microenvironment are needed for sufficient suppression of dormant micrometastases.

KerryMac · May 2011

"ZOL reduced the risk of death by 42% in pts > 40 yr of age, with presumed complete ovarian blockade"

That just made my entire week. Thanks.

YATCOMW · May 2011

This is great news.......thanks for posting!!!!!

I've been on this for many years so glad to hear it helps....

does it say what the frequency of the zometa was?

Jacqueline

YATCOMW · May 2011

Oh.....i see every 6 months.....i had been getting it every two but just switched to six so I guess I am still okay....

whew!!!!

Jacqueline

Celtic_Spirit · May 2011

Thank you, thank you! That news RAWKS!

Gitane · May 2011

Ya, it made me feel pretty good, too.

weety · May 2011

Yay, Yay, Yay!

everyminute · May 2011

I am hopeless with the greater than /less than sign - it is like that part of my brain is missing. Even when I do the L for less than with my hand...

Since I was diagnosed at 39 1/2 I guess that isnt as a big a deal for me personally. If I am reading this correctly (other than <>) they are finding a correlation between complete ovarian blockage (ie hysterectomy, lupron or natrual menapause) and zometa working better?

You are all happy so I will be happy too (I feel like Winnie the Pooh with stuffing in my head!).

I demanded zometa right after chemo and have had it every 6 months "to prevent osteoporosis" oddly enough, it hasnt dont that since I have osteopenia/border line osteporosis but I am still gonna do the happy dance if you tell me to!

weety · May 2011

Yes, everyminute, I think you are interpreting it correctly. There is still a disagreement on whether induced menopause is the same as natural menopause since the studies all seem to focus on postmenopausal >5 yrs (more than 5 yrs from official menopause) but my opinion is that an immediate menopause from ooph must be the same since estrogen is immediately reduced. I was 38 at diagnosis and have just had one zometa treatment so far. I'm due for my next one in June. I won't know if it's helping with my osteopenia for a while--onc won't test for at least a year from first zometa treatment.

Does anyone know if these results also pertain to estrogen negative tumors? I'm just curious because mine was just "weakly" positive and I'm wondering if the study enrolled both receptors or just the positive. If it seems to go along with estrogen ablation, my guess is no, but who knows. . .

Latte · May 2011

my onc didn't want me to do preventative zometa because of the last study that came out, but now i see this and if i understand correctly then i should be pushing to get it. I finished active tx in Feb this year, and 6 weeks after had an ooph. i don'[t quite understand the age thing - why would the situation change between someone who is 39 and 11 months and 40 and 2 months at diagnosis - i'm assuming there has to be a fuzzy line around the 40 year old mark - things don't suddenly change overnight. I was 39.5 at diagnosis, and am now 40.5 - i think i want to fit into the over 40 beneficial category (If i understood the <> signs - i'm also not good with them :-)

Latte · May 2011

one more question - the study refers to early BC - anyone know exactly what "early BC" covers? I'm assuming it doesn't cover stage III? i think my onc told me that my IIIC stage is locally advanced BC.

Anonymous · May 2011

Hello Ladies,

Have been fluttering around for the past two months never minding my stage, but it would be very nice sharing with sisters in same pot...

Would this replace Tamox (I figure one-year on the med has qualified me as menopausal) which I would consider a miracle... or be added to the regimen ?

Latte · May 2011

hi luan,

it's usually in addition to tamox or an AI, not instead of. And tamox for a year won't definitely make you menopausal - you need an E2 estradiol test to be sure of that.

AnacortesGirl · May 2011

I sure hope Aetna is reading these study results!! I'm coming up on my 6 month Zometa and last I heard Aetna was paying because of the Azure results. I definitely have a low estrogen environment!

Latte - for study purposes Stage III is considered early stage. If a study excludes stage III then it will be listed explicitly as an exclusion.

Thanks Gitane!

Anonymous · May 2011

Thanks Latte, am getting the hormone panel done shortly, sounded too good to be true, i mean "instead", am hating Tamox, lots of SEs. Will ask the onco at next visit

Would anyone know what the SEs would be on this Zometa ?

KerryMac - were you ever on Tamox then switched to AIs ?

Thank you everyone, real nice to be talking same language Wink

Latte · May 2011

luan - i think that the SEs on zometa are a possible flu-like feeling for a day or 2 after the infusion, plus the rare chance of jaw problems.

suzanneinphoenix · May 2011

Luan;

I had one zometa infusion....I could not handle the particular SE's I had. They mentioned 'flu like symptoms"...but I had really bad indigestion all night the first night. And I had severe muscle spasms at night for at least a week after it. They said those symptoms could happen again... so I opted out. Wish I could have handled it......

Gitane · June 2011

Back on May 19 I posted this ASCO abstract. I feel really good about these results because I am postmenopausal (over 5 years), way over 40 years old, and seem to fit the criteria of those who benefit. There may be some good things about treatment, even if the SE's are not what we'd want and the treatments are expensive. Abstract:Background: Adjuvant zoledronic acid (ZOL) significantly improved disease-free survival (DFS) in premenopausal patients (pts) with endocrine-responsive early breast cancer in ABCSG-12 (Gnant et al. NEJM 2009). The ZOL anticancer effect was confirmed in other prospective trials, such as ZO-FAST and the postmenopausal (> 5 yrs) cohort of AZURE. Long-term follow-up of ABCSG-12 (> 6 yr) now allows pre-planned subgroup analyses that more precisely identify the ZOL benefit, and interactions with pt and tumor characteristics. Methods: Premenopausal pts with early breast cancer (N = 1,803) were randomized to ovarian function suppression with goserelin (3.6 mg q28d) and tamoxifen (TAM; 20 mg/d) or anastrozole (ANA; 1 mg/d) ± ZOL (4 mg q6mo) for 3 yr. Endpoints included DFS and overall survival (OS), both analyzed using log-rank test and Cox models. Preplanned subgroup analyses included subpopulation treatment effect pattern plot (STEPP). Results: At 68 mo median follow-up, ZOL significantly reduced the risk of DFS events by 32% vs no ZOL (HR = 0.68; P = .009); in addition, there was a strong trend toward reduced risk of death (HR = 0.66; P = .08) with ZOL vs no ZOL. Multivariate analyses showed no interaction between ZOL benefit and ANA/TAM or any classic tumor parameter (eg, T, N, grade, ER). However, a strong interaction between ZOL and pt age was demonstrated. Pts > 40 yr of age (n = 1,390) derived significant DFS benefits from ZOL (HR = 0.58; 0.40-0.83; P = .003), whereas there was no apparent benefit in pts < 40 yr of age. ZOL reduced the risk of death by 42% in pts > 40 yr of age (P = .05), with presumed complete ovarian blockade. In several age subgroups > 40 yr, HRs < 0.5 were observed for both DFS and OS. Conclusions: ABCSG-12 long-term follow-up at 68 mo suggests that anticancer benefits of adjuvant ZOL mainly occur in pts with a low-estrogen environment. As in the postmenopausal (> 5 yrs) cohort of AZURE, ZOL leads to highly significant DFS and OS benefits. This suggests that both estrogen deprivation and reduction of bone-turnover–derived growth factors in the bone marrow microenvironment are needed for sufficient suppression of dormant micrometastases.

Pure · June 2011

My Doctor who pulled it from my tx called me last week after reviewing this study at the conference. They put me back on it-I go Tuesday. I don't care what th SE"s. lol I can live with a bromen femur bone but my cancer will kill me. But yes in addition to the jaw issues several reported cases of women randomly breaking their femur bone. There are law suits going on as well but still I will take the zomtea all day long.

Stage 1-3 is early-advanced is stage 4.

lkc · June 2011

Thanks for posting this. I am a huge advocate of Z!!!

karen1956 · June 2011

When I was on AI's i was on Actonel...I asked my onc about Zometa and it felt that the Actonel provided similar benefits....I didn't push him as I really didn't want to be in the infusion room....I've been off AI's for 15 months now and also stopped the Actonel...I take calcium with mag....due for a bone density this fall (now only have them done every 2 years as that is protocol for women not on AI's)....I don't know how I feel about things anymore....See my onc in August, so may just see what he says....but if he doesn't bring it up, I probably won't....maybe I'm in denial land!!!

Zoledronic Acid Update

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