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Aromatase Inhibitors

Updated 15 Dec 2004

Comment from the Westmead Breast Cancer Institute.
Prof John Boyages (Director)

1. American Society for Clinical Oncology (ASCO) (Technology Assessment)- Use of Aromatase Inhibitors in the Adjuvant Setting (

Nov 15 2004 Journal of Clinical Oncology 

Eric P. Winer * et al. From Cancer Policy and Clinical Affairs, American Society of Clinical Oncology, Alexandria, VA.

  • Anastrazole (Arimidex) is available from Dec 1 on the PBS for Australian women who do not tolerate or have a contraindication to Tamoxifen such as a history of blood clots or endometrial cancer.

  • We have about 30 years of data on Tamoxifen and when trials of 5 vs 10 years were undertaken, a higher incidence of endometrial cancer was discovered.  We need to be aware that long-term follow-up outcome data or toxicity data are still awaited.

  • The data suggest that we should consider an AI after 5 years of Tamoxifen.  The MA17 trial showed a benefit after 5 years of Tamoxifen for Letrozole (Femara)  This is currently not funded by the PBS and may cost your patient $200-$300 per month

  • The benefit of these drugs is less as the risk of recurrence is lower.  A web site can determine the added benefit of 5 years of Letrozole over and above Tamoxifen (www.adjuvantonline.com). This site is for doctors. Please note, the authors of this web site recommend using “mortality” data rather than “recurrence” data (which are less precise as they often include the risk of opposite breast cancer, local recurrence or death from other causes).

  • AIs have a higher risk of osteoporosis and hip fracture and bone density should be monitored whilst patients are taking these drugs.

2. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer

Lancet: Volume 364, Number 9450     04 December 2004

  • Postmenopausal women talking Tamoxifen should talk to their doctors about the new options" and weigh up the risks and benefits (see Table below) including the costs involved.

  • In Australia, Arimidex is funded on the Pharamaceutical benefits (PBS) scheme as additional treatment following surgery +/- radiotherapy (“Adjuvant Therapy”) for patients who do not tolerate Tamoxifen.

  • Aromatase inhibitors are funded by the PBS for patients with advanced disease
     

  Arimidex Tamoxifen p   Absolute
          Difference
No of Patients 3092   3094      
       
Recurrence 18.6%   21.0%   0.01   -2.4%
         
Distant Metastases 10.5%   12.1%   0.04   -1.6%
         
Opposite Breast Cancer 1.1%   1.9%   0.01   -0.8%
               
Overall Survival "Similar"   NS    
   
Complications              
Hot flushes 36%   41%   <0.0001   -5.0%
Nausea and vomiting 13%   12%   NS   1.0%
Fatigue 19%   18%   NS   1.0%
Mood disturbances 19%   18%   NS   1.0%
Arthralgia 36%   29%   <0.0001   7.0%
Vaginal bleeding 5%   10%   <0.0001   -5.0%
Vaginal discharge 4%   13%   <0.0001   -9.0%
Endometrial cancer 0.2%   0.8%   0.02   -0.6%
Fractures 11%   8%   <0.0001   3.0%
Ischaemic cardio-vascular disease 4%   3%   NS   1.0%
Ischaemic cerebro-vascular disease 2%   3%   0.03   -1.0%
Venous thrombo-embolism 3%   5%   0.0004   -2.0%
Deep venous thromboembolism 1.6%   2.4%   0.02   -0.8%
Cataracts 6%   7%   NS   -1.0%
 
    =Arimidex significantly better
    =Tamoxifen significantly better 

Summary of the ATAC trial:

  1. 3092 women had Anastrazole (A) and 3094 Tamoxifen (T)

  2. 575 pts had a recurrence (A)(18.6%) vs 651 (T) (21%)

  3. Absolute benefit of A over T (2.4%)

  4. Benefit seems to increase over time (projected 6 yr benefit = 3.7%)

  5. No difference in death rates so far (but probably too early to tell but unlikely to be greater than 2%)

  6. A lot of the improvement from A is from reducing the risk of opposite breast cancer

  7. Reduced incidence of Treatment with anastrozole was associated with significant reductions in the incidence of endometrial cancer (0.2% vs 0.8%), blood clots (2.8% vs 4.5%), hot flushes (36% vs 41%) and vaginal discharge(3.5% vs 13.2%)

  8. Tamoxifen was associated with fewer fractures (11% A vs 7.7% T)and less aches and pains than anastrozole (36% A vs 29% T).

  9. Fracture rates per 1000 woman-years were 22·6 for anastrozole and 15·6 for tamoxifen The incidence of hip fracture was low and similar for anastrozole and tamoxifen.

Comments from the ASCO technical report:

  • Patients may substitute an aromatase inhibitor for tamoxifen as initial therapy. – (not funded in Australia as yet except for patients who are intolerant of Tamoxifen)

  • Patients can still begin treatment with tamoxifen and switch to an aromatase inhibitor after two to five years. (not funded in Australia as yet except for patients who are intolerant of Tamoxifen)

  • Patients now taking tamoxifen may consider switching to an aromatase inhibitor after two to five years on tamoxifen. (not funded in Australia as yet except for patients who are intolerant of Tamoxifen)

  • Patients who switch to an aromatase inhibitor may continue the therapy for two to three more years, but no longer than five years. Treatment with an aromatase inhibitor for longer than five years has not been studied.

  • It is still not entirely clear whether it's better for women to start with an aromatase inhibitor immediately or start with tamoxifen and then switch to an aromatase inhibitor.

  • There are no data to recommend taking tamoxifen after an aromatase inhibitor.

  • Tamoxifen remains the best option for younger women who still have functioning ovaries. That's because aromatase inhibitors aren't powerful enough to stop the production of oestrogen in ovaries.

A/Prof John Boyages, Executive Director, Westmead Breast Cancer Institute
Dr Nicholas Wilcken, Research Director, Westmead Breast Cancer Institute

Last Updated on Tuesday, 09 February 2010 12:24