aromatase inhibitors, femara or arimidex

Here are some links.

I looked for the New England Journal article but all the ones I found were pay for view.

I searched NCBI and came up with the following. I also include the general link to the search result - plenty to look at if you have time and the subject is of interest.

No 15 looked useful being informative, gives comparative statistics side effects etc fro the AIs, and is not too technical so I have also posted a link on articles of interest.

RB

Clinical Update

The aromatase inhibitors in early breast cancer: who, when, and why?
Ilona C Nordman, Andrew J Spillane and Anne L Hamilton

http://www.mja.com.au/public/issues/...r10037_fm.html

Abstract

*

The aromatase inhibitors deplete oestrogen by inhibiting aromatase, the enzyme that synthesises oestrogen from androgens. They are effective as therapies for breast cancer only in postmenopausal women whose tumours express oestrogen or progesterone receptors.
*

As adjuvant therapy, tamoxifen and the aromatase inhibitors have similar efficacy in the first 5 years of treatment. Aromatase inhibitors can be used as an alternative to tamoxifen in women with symptomatic intolerance or a contraindication to tamoxifen.
*

Early data suggest that switching to an aromatase inhibitor after 2–5 years of tamoxifen therapy is beneficial in women with high-risk disease.
*

Aromatase inhibitors are associated with more hot flushes than placebo, but with fewer hot flushes, less endometrial toxicity and venous thromboembolism, and more arthralgia, myalgia and bone fracture than tamoxifen.........


http://159.54.227.3/apps/pbcs.dll/ar.../51228053/1003

ABSTRACT

A study reported earlier this year in Europe and published in Thursday's New England Journal of Medicine estimated that 84 percent of women given Femara versus 81 percent of those on tamoxifen would be alive without any signs of cancer five years after starting treatment.


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: MedGenMed. 2005 Aug 24;7(3):20. Related Articles, Links
Click here to read
Benefit with aromatase inhibitors in the adjuvant setting for postmenopausal women with breast cancer.

Mouridsen HT, Robert NJ.

Department of Oncology, Rigshospitalet, Copenhagen, Denmark.

The third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, have been shown to be effective both as alternatives to tamoxifen in first-line treatment of hormone-sensitive advanced breast cancer in postmenopausal women and following failure of first-line tamoxifen for endocrine therapy. These 3 agents are now being investigated as adjuvant therapy of early breast cancer, as alternative or complementary treatments to the standard, tamoxifen. Three treatment strategies are under investigation: replacement of tamoxifen as adjuvant therapy for 5 years (early adjuvant therapy), sequencing of tamoxifen before or after an aromatase inhibitor during the first 5 years (early sequential adjuvant therapy), or following 5 years of tamoxifen (extended adjuvant therapy). In the first adjuvant trial (Arimidex, Tamoxifen Alone or in Combination [ATAC]), anastrozole was significantly superior to tamoxifen in reducing risk of disease recurrence, and recently, the Breast International Group (BIG) trial BIG 1-98 demonstrated the significant superiority of letrozole over tamoxifen in improving disease-free survival. A large trial (International Collaborative Cancer Group [ICCG] trial 96) investigated sequencing of 2 to 3 years of exemestane after 2 to 3 years of tamoxifen and found that switching to exemestane was significantly superior in disease-free survival compared with continuing on tamoxifen. The Arimidex or Nolvadex (ARNO) and the small ITA (Italian Tamoxifen Arimidex) trials similarly sequenced anastrozole after tamoxifen and also found that sequencing reduced the hazard of recurrence compared with remaining on tamoxifen. Trial MA.17 evaluated extended adjuvant therapy with letrozole vs placebo following 5 years of tamoxifen. Disease-free survival was significantly improved with letrozole vs placebo, irrespective of whether patients had lymph node-positive or node-negative tumors. All 3 aromatase inhibitors were generally well tolerated. Results of these trials indicate that aromatase inhibitors provide important benefits relative to tamoxifen in each of these adjuvant treatment settings, but the optimal approach still needs to be defined. Other trials continue to investigate some of these adjuvant treatment strategies.

PMID: 16369246 [PubMed - in process]



http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Clin Ther. 2005 Nov;27(11):1671-84. Related Articles, Links

Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer.

Berry J.

BACKGROUND:: Five years of tamoxifen therapy hasbeen the standard of care for the adjuvant treatment of estrogen receptor-positive early-stage breast cancer for many years and was the first hormonal treatment for postmenopausal women with advanced or metastatic disease. The third-generation aromatase inhibitors (AIs) anastrozole, exemestane, and letrozole offer new treatment options, although their efficacy has not been compared directly in randomized, double-blind, controlled trials in any breast cancer treatment setting. OBJECTIVE:: The goal of this article was to review theresults of recent randomized, controlled clinical trials of the AIs in the settings of neoadjuvant, adjuvant, and advance d/metastatic breast cancer. METHODS:: MEDLINE was searched for descriptions of randomized, controlled clinical trials published from 1990 to 2005 using the terms breast cancer, aromatase, aromatase inhibitor, anastrozole, exemestane, and letrozole. Abstracts from the proceedings of several oncology meetings held between 2001 and 2005 were searched to capture relevant emerging data. RESULTS:: In 2 Phase III trials comparing an AI withtamoxifen for the adjuvant treatment of breast cancer in postmenopausal women, disease-free survival was significantly improved with anastrozole and letrozole compared with tamoxifen as initial adjuvant treatment (P = 0.01 and P = 0.003, respectively). A switch to either anastrozole (2 Phase III trials) or exemestane (1 Phase III trial) after 2 to 3 years of adjuvant tamoxifen therapy was more effective in reducing the risk of recurrence than continued tamoxifen therapy (P = 0.006, P < 0.002, and P < 0.001, respectively); data on switching to letrozole are expected soon. In another Phase III trial, letrozole was found to improve disease-free survival in the extended adjuvant setting (P :</= 0.001) and was the only AI consistently more effective than tamoxifen in the neoadjuvant setting. In 3 Phase III studies (1 letrozole vs tamoxifen, 2 anastrozole vs tamoxifen), both anastrozole and letrozole were more efficacious than tamoxifen in the first-line setting, and some patients receiving letrozole had better overall response rates compared with those receiving anastrozole in the second-line setting (19.1% vs 12.3%, respectively; P = 0.013). In a patient-preference study, those receiving letrozole reported fewer adverse events than those receiving anastrozole (43% vs 65%; P < 0.003), and more patients preferred letrozole to anastrozole (68% vs 32%; P < 0.01). CONCLUSIONS:: Currently, anastrozole and letrozoleare associated with the most complete data over the breast cancer care continuum, with efficacy in early-stage, locally advanced, and metastatic disease. In-direct comparisons suggest stronger evidence for the use of letrozole compared with other AIs for breast cancer in postmenopausal women who require estrogen-deprivation therapy. Data from randomized, double-blind comparative studies will help clarify the differences between AIs.


http://www.ncbi.nlm.nih.gov/entrez/q...moxifen+femara

1: Rao GG, Miller DS. Related Articles, Links
Abstract Hormonal therapy in epithelial ovarian cancer.
Expert Rev Anticancer Ther. 2006 Jan;6(1):43-47.
PMID: 16375643 [PubMed - as supplied by publisher]

2: Mouridsen HT, Robert NJ. Related Articles, Links
Free Full Text Benefit with aromatase inhibitors in the adjuvant setting for postmenopausal women with breast cancer.
MedGenMed. 2005 Aug 24;7(3):20.
PMID: 16369246 [PubMed - in process]

3: Berry J. Related Articles, Links
Abstract Are all aromatase inhibitors the same? A review of controlled clinical trials in breast cancer.
Clin Ther. 2005 Nov;27(11):1671-84.
PMID: 16368441 [PubMed - in process]

4: Howell A, Locker GY. Related Articles, Links
Abstract Defining the roles of aromatase inhibitors in the adjuvant treatment of early-stage breast cancer.
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5: Jonat W, Hilpert F, Maass N. Related Articles, Links
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6: Kijima I, Itoh T, Chen S. Related Articles, Links
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PMID: 16263272 [PubMed - in process]

7: Vergote I, Abram P. Related Articles, Links
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Ann Oncol. 2005 Oct 26; [Epub ahead of print]
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8: Abrial C, Mouret-Reynier MA, Cure H, Feillel V, Leheurteur M, Lemery S, Le Bouedec G, Durando X, Dauplat J, Chollet P. Related Articles, Links
Abstract Neoadjuvant endocrine therapy in breast cancer.
Breast. 2005 Oct 14; [Epub ahead of print]
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9: Howell A. Related Articles, Links
Abstract New developments in the treatment of postmenopausal breast cancer.
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PMID: 16213745 [PubMed - in process]

10: Chowdhury S, Ellis PA. Related Articles, Links
Abstract Recent advances in the use of aromatase inhibitors for women with postmenopausal breast cancer.
J Br Menopause Soc. 2005 Sep;11(3):96-102. Review.
PMID: 16157000 [PubMed - indexed for MEDLINE]

11: Carlini P, Bria E, Giannarelli D, Ferretti G, Felici A, Papaldo P, Fabi A, Nistico C, Di Cosimo S, Ruggeri EM, Milella M, Mottolese M, Terzoli E, Cognetti F. Related Articles, Links
Abstract New aromatase inhibitors as second-line endocrine therapy in postmenopausal patients with metastatic breast carcinoma: a pooled analysis of the randomized trials.
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Abstract Safety considerations of adjuvant therapy in early breast cancer in postmenopausal women.
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13: Weinberg OK, Marquez-Garban DC, Pietras RJ. Related Articles, Links
Abstract New approaches to reverse resistance to hormonal therapy in human breast cancer.
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15: Nordman IC, Spillane AJ, Hamilton AL. Related Articles, Links
Free Full Text The aromatase inhibitors in early breast cancer: who, when, and why?
Med J Aust. 2005 Jul 4;183(1):24-7. Review.
PMID: 15992333 [PubMed - indexed for MEDLINE]

16: Howell A. Related Articles, Links
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PMID: 15831674 [PubMed - indexed for MEDLINE]
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PMID: 16368441 [PubMed - in process]

[lia]

I think i read on the reports of the recent conference that arimidex had the best results on the ATAC trials with er+ pr- bc, femara as i remember worked equally well with er+ pr+, and er+ pr -, or at least wasnt adversley affected by pr receptor status. I m in my 4 th week of arimidex and have just had my second zoladex injection, so far it s not been too bad, although my GGT levels were elevated in my last blood chemistry i m not sure if that could be down to zoladex arimidex or the 2 glasses of wine i had the week before !! Does anyone know anything more about the best aromatase inhibitors for er and pr receptive bc ? thanks !!

[Ginagce]

Not exactly what you're after but thought this article interesting enough to post.

Newer drug effective against early breast cancer
Femara works better than Tamoxifen at preventing recurrence, study finds
The Associated Press

Updated: 5:26 p.m. ET Dec. 28, 2005



A second member of a new class of drugs has proved more effective than the gold standard, tamoxifen, at preventing breast cancer from recurring in women who received the medicine as initial therapy right after surgery.

The drug, Femara, is expected to win Food and Drug Administration approval soon for women who are past menopause and have early breast cancer. It is already approved for treating advanced cases of the disease.

Femara and Arimidex, a similar drug already licensed for early breast cancer, are aromatase inhibitors, which block production of estrogen, a hormone that fuels the growth of most tumors that develop after menopause. Tamoxifen works differently, by blunting the ability of estrogen to enter cells.

A study reported earlier this year in Europe and published in Thursday’s New England Journal of Medicine estimated that 84 percent of women given Femara versus 81 percent of those on tamoxifen would be alive without any signs of cancer five years after starting treatment.

The estimates were based on roughly two years of information on relapses among the 8,000 women in the study, done by researchers in the United States, Europe and Australia.

It was financed by Femara’s maker, Novartis. Many of the researchers own stock in or are consultants for Novartis or companies with rival drugs.

Several other studies have shown Femara or Arimidex to be better either as initial treatment or after a couple years of tamoxifen.

“These trials, with close to 30,000 participants, consistently demonstrate that treatment with an aromatase inhibitor alone or after tamoxifen treatment is beneficial,” Dr. Sandra Swain of the National Cancer Institute wrote in an editorial in the journal.

The challenge now is figuring out how long women should take these drugs, which drug is best, and whether switching drugs at some point is helpful, she wrote.

Tamoxifen remains the top choice for women who get breast cancer before menopause because aromatase inhibitors aren’t thought to be effective then.

Aromatase inhibitors do not raise the risk of blood clots or endometrial cancer as tamoxifen does, but they do increase the chances of bone problems such as osteoporosis. Women are often advised to take supplements or other medications to maintain bone density.

A third aromatase inhibitor, Pfizer Inc.’s Aromasin, also has shown promise for preventing recurrence when given after several years of tamoxifen. But it has not yet been tested against tamoxifen as initial therapy the way Femara and AstraZeneca PLC’s Arimidex have been.

Each year, about 800,000 women around the world are diagnosed with early breast cancer and about three-fourths are of the type that might benefit from these drugs.

© 2005 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

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[Diane H]

Wow, what awesome info. Lia, I was especially interested in the ER+ PR- study. Will look that one up. And Gingace brought up an interesting study that asks another question, how long should we stay on these AI's.

[lia]

http://clinicaloptions.com/Oncology/...vant%20Therapy

This is my first attempt at posting a link , dont know if it will work ..but this is where i first read about arimidex working better for er+ pgr - than er+ pgr+ in the ATAC trials, but i dont think this is the article that said that femara was equally good regardless of pgr status, to paraphrase it probably very simplistically ! It was definitely somewhere on this clinical options site which you have to register to use , when i find it i will repost... and attempt to print it out to show my oncologist who i ve only just persuaded to let me have arimidex !!

I put "arimidex working better for er+ pgr - than er+ pgr+" into google and heres the first four that came which all relate to the search term.

The medscape link also includes a section on herceptin. It is free you just have to register. I have included an abstract on ER and Tamoxifen, and the use of oncogene testing.

RB


http://www.susanlovemd.org/community...usa_mayer.html

http://www.annieappleseedproject.org/notfromadper.html

http://www.jco.org/cgi/content/full/22/9/1605

http://www.medscape.com/viewprogram/4205_pnt

Abstract


Molecular Predictors of Tamoxifen Benefit

One of the most exciting diagnostic tools to emerge in recent years has been the OncotypeDX recurrence score assay from Genomic Health. This assay quantifies the expression of 21 genes in breast tumors based on RNA retrieved from paraffin-embedded, formalin-fixed tissue. The recurrence score has been translated into an absolute risk of tumor recurrence through 10 years of follow-up among women with ER+, node-negative breast cancer. Investigators[9] from the National Surgical Adjuvant Breast and Bowel Project (NSABP) have sought to determine whether this recurrence score, which appears to risk-stratify patients very successfully, can also predict which tumors benefit from tamoxifen. They characterized the recurrence score for tumors of patients in NSABP B-14, a randomized trial of placebo vs tamoxifen. Patients in B-14 had node-negative, ER+ tumors. Previous studies had shown that the lower the recurrence score, the lower the risk of recurrence. New data have used the recurrence score to determine which patients may benefit from tamoxifen (Table 2).
Table 2. Recurrence Score and Tamoxifen Benefit in NSABP B-14
Recurrence Score 10-Year Distant
Disease Free Survival Gains With Tamoxifen
Placebo Tamoxifen Absolute
Benefit Relative
Risk Reduction
Low (< 18) 85.9% 93.1% 7.2% 51%
Intermediate (18-30) 62.5% 79.5% 17.3% 46%
High (> 30) 68.7% 70.3% 1.6% 5%

These data suggest the following: First, tamoxifen dramatically reduces the risk of recurrence in some, but not all breast cancers. Tumors with low or intermediate recurrence scores, which tend to have higher levels of ER expression, grade 1-2 features, and be HER-2-negative, derive tremendous benefit from tamoxifen treatment, with nearly 50% reduction in risk. By contrast, tumors with high recurrence scores, which tend to be lower ER expressors and to have poorly differentiated features and sometimes HER-2 expression, derive minimal benefit from tamoxifen. Previous research by the same group has shown that patients with these high-recurrence-score tumors derive substantial benefit from chemotherapy. It is important to note that these data refer only to patients treated with tamoxifen; whether the recurrence score is valid among patients treated with an AI is not known.

A key clinical point is that we can now refine our understanding of which patients have a more favorable prognosis due to tumor sensitivity to tamoxifen, and conversely, which patients may yet derive substantial benefit from chemotherapy because they are relatively insensitive to endocrine manipulation. Thus, this type of testing has the potential to dramatically refine patient selection for important adjuvant clinical treatments.

Here is a link to the "FULL PERSCRIBING INFORMATION" for femara.

PAGE 5 has a table of DFS disease free survival by receptor status nodal status etc.

It looks like a VERY useful document for those who are specifically interested. I am out of my depth as to the various significances of disease classification.

RB

http://www.fda.gov/cder/foi/label/20...726s011lbl.pdf

[CLTann]

Regarding Arimidex versus Tamoxifen, the effectiveness is reportedly to be 84% versus 81%. The NEJM article concluded that Arimidex (or Femara) is much superior than Tamoxifen.

I don't know where these doctors received their education. From my school training and statistics, I wouldn't call 84 versus 81 a very significant major break through. The poor patients in the 16 or 19 group are equally suffering. Looking back also on the efficacy of Herceptin in the NEJM recently, there was a similar undue exuberance on the data. The recurrence rate after Herceptin treatment was still very high.

I don't want to sound like a pessimist. Any forward movement to conquor this dreadful disease is always a welcome step. Nevertheless, we need to be scientifically and factually realistic, and put all data under correct perspective. The editorial on Herceptin in the October NEJM issue was simply overstepping the boundary of honest reporting and give readers a false sense of security. Medical research is indeed making rapid headway, but we are far from resolving this difficult problem yet. Meanwhile, we need to remain alert and strong, using all tools available to us, diligently and persistently in the search of the best defense plan on an individual basis.

Ann

[lia]

I spent ages last night googling (!!) and am no less confused ! Basically my understanding is that arimidex is better than tamoxifen for her2 , but that generally ( ie not taking her2 as a consideration ) 2 yrs of tamoxifen then 3 of arimidex is best for er+ pgr+ bc which is what i am... along with her2 +. I cant find the references to femara and er/pgr + anywhere... I m sure I read it in the clinical options site but cannot find it now.I will continue to search.... the problem is( and i m sure everyone else has found this too ! ) that her2 is almost a law unto itself and there s not enough written about it, on breastcancer. org i read that her2 bc is more likely to be hormone receptor negative , which was quoted to me back in feb. which is probably true but doesnt help much when you are n't. So sorry if i ve further confused anyone !

Page 5 line 174 suggests they did look at er and pgr+ if that is the same thing, but I could not find a table of separate results but maybe if you entered the trial details into NCBI or google the full trial if available /findable may help - how about emailing Novartis?.



RB

http://www.fda.gov/cder/foi/label/20...726s011lbl.pdf