Breast Cancer Guidelines Confirm Central Role of 'Switch Strategy'; Recommendations of St Gallen Panel Support Exemestane Indication

Guidelines from the 2007 St Gallen International Expert Consensus
on the Primary Therapy of Early Breast Cancer, published today in the
Annals of Oncology (http://annonc.oxfordjournals.org), confirm the
value of switching from tamoxifen to an aromatase inhibitor (AI), such
as exemestane, for the adjuvant treatment of postmenopausal women with
hormone receptor positive early breast cancer.(i)

Approximately 360,000 women in Europe are diagnosed with breast
cancer each year. With up to two thirds of breast cancers requiring
the hormone estrogen to grow, medicines such as exemestane are crucial
for women affected by this disease, because they work by interfering
with the supply of estrogen to the cancer and preventing it from
growing. Switching from tamoxifen to exemestane has the potential to
save lives among women diagnosed with hormone receptor positive early
breast cancer.(ii)

The St Gallen guidelines are the consensus of breast cancer
experts from around the world, who have assessed and recommended
optimal treatment strategies for this disease, which affects the lives
of thousands of women and their families.

"Guidelines are essential for physicians, as they ensure we are up
to date with the latest recommendations for patient care," said
Professor Charles Coombes, Head, Department of Oncology, Imperial
College, London. "The St Gallen guidelines have confirmed the value of
starting treatment with tamoxifen then switching to an aromatase
inhibitor, enabling women to benefit from the advantages of both
medicines. Exemestane, one of the aromatase inhibitors, has been
proven to offer an overall survival benefit in the switch setting, and
these latest guidelines confirm to physicians that we should continue
to use it in this way to offer patients the very best care."

In hormone receptor positive breast cancer, the St Gallen panel
expressed a clear preference for switching patients from tamoxifen to
an AI, such as exemestane, which means more patients can benefit from
exemestane's proven results in extending lives.

The guidelines follow publication of the Intergroup Exemestane
Study (IES) in The Lancet earlier this year, which showed an overall
survival benefit for women who switched from tamoxifen to exemestane,
the only AI to have demonstrated overall survival in a single,
double-blind trial.(ii) The IES, which randomized 4,724 patients
across 37 countries, demonstrated that postmenopausal women(1) with
early breast cancer, who switched to exemestane after 2-3 years of
tamoxifen, experienced a 17% reduction in the risk of death compared
to those who stayed on tamoxifen for the full 5 years of therapy.(ii)
Exemestane was the first AI to receive approval in the switch setting.

Professor Coombes, who was lead investigator of the IES,
continued, "The IES results, and now the St Gallen guidelines, confirm
that switching to exemestane rather than staying on tamoxifen gives
women an improved chance of survival. Furthermore, switching to
exemestane has also been proven to have no significant adverse effect
on quality of life compared to tamoxifen alone,(iii) making it a good
all-round option for women."

About exemestane (iv)

Exemestane is currently indicated for the adjuvant treatment of
postmenopausal women with estrogen receptor positive invasive early
breast cancer who have received 2-3 years of tamoxifen and are
switched to exemestane for the completion of a total of 5 consecutive
years of adjuvant hormonal therapy. Exemestane is also indicated for
the treatment of advanced breast cancer in women with natural or
induced postmenopausal states, whose disease has progressed following
anti-estrogen therapy.

Exemestane should not be used in women who are premenopausal, are
nursing or pregnant, have a known hypersensitivity to the drug, or are
taking estrogen-containing agents. Exemestane should be used
cautiously with drugs that are metabolised via CYP3A4 and have a
narrow therapeutic window.

Exemestane was generally well tolerated across all clinical
studies; undesirable effects were usually mild to moderate. The
withdrawal rate due to adverse events in studies was 6.3% in patients
with early breast cancer receiving adjuvant treatment with exemestane
following initial adjuvant tamoxifen therapy and 2.8% in the overall
patient population with advanced breast cancer receiving the standard
dose of 25 mg. In patients with early breast cancer the most commonly
reported adverse reactions were hot flushes (22%), arthralgia (17%)
and fatigue (17%). In patients with advanced breast cancer the most
commonly reported adverse reactions were hot flushes (14%) and nausea
(12%). Most adverse reactions can be attributed to the normal
pharmacological consequences of estrogen deprivation (e.g. hot
flushes).

(1) Women with estrogen receptor positive or unknown status of
disease.

(i) Goldhirsch A, Wood WC, Gelber RD et al. Progress and promise:
highlights of the international expert consensus on the primary
therapy of early breast cancer 2007. Ann Oncol 2007; 18: 1133-1144.

(ii) Coombes RC et al. Survival and safety of exemestane versus
tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane
Study): a randomised controlled trial. Lancet. 2007 Feb
17;369(9561):559-70

(iii) Fallowfield LJ et al. Quality of Life in the Intergroup
Exemestane Study (IES) - a Randomized Trial of Exemestane versus
Continued Tamoxifen after 2-3 years of Tamoxifen in Postmenopausal
Women with Primary Breast Cancer. Journal of Clinical Oncology. Vol
24, No 6, Feb 20, 2006

(iv) Exemestane prescribing information (Summary of Product
Characteristics dated 24 August 2005)