Herceptin/Arimidex Improves PFS in Metastatic Breast Cancer

November 1, 2006

Adding trastuzumab (Herceptin) to anastrozole (Arimidex) as adjuvant therapy for postmenopausal women with so-called copositive (hormone-receptor-positive, HER2-positive) metastatic breast cancer signficantly improved progression-free survival (PFS), compared with anastrozole alone, according to a study presented at the 31st Congress of the European Society for Medical Oncology (ESMO) (Late Breaking Abstract 2).

ISTANBUL, Turkey--Adding trastuzumab(Herceptin) to anastrozole(Arimidex) as adjuvant therapy for postmenopausalwomen with so-called copositive(hormone-receptor-positive,HER2-positive) metastatic breast cancersignficantly improved progression-freesurvival (PFS), compared with anastrozolealone, according to a study presentedat the 31st Congress of the EuropeanSociety for Medical Oncology(ESMO) (Late Breaking Abstract 2).

Up to 15% of all metastatic breast cancersare positive for both the estrogenreceptor (ER) and HER2, said lead investigatorBella Kaufman, MD, of ChaimSheba Medical Center, Ramat Gan, Israel.Evidence of crosstalk between theestrogen-receptor and HER2 signalingpathways suggests that simultaneous targetingof both pathways in women withco-positive disease may result in greaterantitumor activity than either agent alone,she explained.

"Currently, the majority of thesewomen are treated with chemotherapyand trastuzumab," she said, "but wethought it might be possible to achievethe same result without the toxicity ofchemotherapy. Also, 20% of the ER-positivepopulation is treated with hormonaltherapy alone, and, for them, the combinationoffers benefit."

Dr. Kaufman and her colleagues conductedan open-label, phase III study,known as TAnDEM and sponsored byRoche, which markets Herceptin internationally.They enrolled 208 patients at77 centers in 22 countries. Eligible patientswere postmenopausal women withHER2-positive (IHC 3+ and/or FISH+)and ER-positive and/or progesterone(PR)-positive metastatic breast cancer.Patients received anastrozole 1 mg/dorally or anastrozole plus trastuzumab4 mg/kg IV infusion on day 1, then 2mg/kg once weekly, until progression.Women who progressed on the singledrug were switched to the combination.

Median progression-free survival, theprimary endpoint, doubled with the combinationregimen, from 2.4 months forthose on anastrozole alone to 4.8 monthsfor those on anastrozole/trastuzumab(P = .0016). Median overall survival wasalso prolonged in the combination arm:28.5 months vs 23.9 months (P = .325)."This difference was not statisticallysignificant," Dr. Kaufmansaid. She noted, however, thatthe trend toward longer survivalwas achieved despite thefact that 73 patients (35%)crossed over from the singledrugarm when their diseasestarted to progress.

The overall response rate in 147 patientsevaluable for response was threefoldhigher with the combination--20.3% vs 6.8% for anastrozolealone (P = .018).

"The results are very positive,"Dr. Kaufman said at anESMO press briefing. "Inbreast cancer, there are notmany trials that show doubleprogression-free survival." Sheadded that the overall safety in both armswas acceptable, noting that the quality oflife of the women in the trial was mostlikely better than if they had been receivingchemotherapy instead.