Intarcia breast cancer therapy enters phase III

Intarcia’s objective with the combined anti-estrogen therapy (CAT) study is to test the hypothesis that its combination of atamestane plus toremifene (Orion Pharma’s Fareston) will be more active than single agent therapy with letrozole (Novartis’ Femara) alone.

“By complementary mechanisms of action, the combination of estrogen receptor blockade and aromatase inhibition addresses both key mechanisms by which estrogen drives breast cancer cell growth,” explained Alice Leung, CEO of Intarcia Therapeutics. “This offers the opportunity to maximize the effectiveness of hormonal therapy in women with hormone-dependent advanced breast cancer.”

“Unlike previous combinations, our approach focuses on selecting the appropriate non-interacting aromatase inhibitor and the estrogen receptor blocker with the least estrogenic activity,” added says Dr Peter Langecker, chief medical officer and vice president of clinical research at Intarcia Therapeutics. “The start of the CAT study, our second pivotal phase III study using combination hormonal therapy, is concurrent with the completion of the enrollment of our first pivotal study.”

Estrogen receptor blockers, such as toremifene, act by blocking the stimulatory action of estrogen at the estrogen receptor on the breast cancer cell. Intarcia believes that a more complete suppression of tumor growth requires the simultaneous elimination of estrogen synthesis and blockade of estrogen receptor stimulation by a compound that by itself is less estrogenic than the controversial tamoxifen.

Intarcia believes this can only be achieved by the combination of these two classes of drugs.

An earlier phase II study showed that atamestane alone is active in postmenopausal women with recurrent hormone dependent breast cancer who had failed previous tamoxifen therapies. The drug significantly lowered estrogen levels and prevented tumor growth for a median of seven months, suggesting significant anti-tumor activity.