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564 Background: Temsirolimus (tem, CCI-779), a novel mTOR inhibitor, is well tolerated and has antitumor activity in heavily pretreated patients (pts) with metastatic breast cancer (MBC, Proc ASCO 22:193,2003). In this trial, we evaluate safety and activity of oral tem in combination with letrozole. Methods: Patients with measurable MBC were randomized in a 1:1:1 ratio (∼30 evaluable pts/arm): 1) letrozole alone or letrozole with 2) tem daily (tem daily arm) or 3) tem daily for 5 days every 2 weeks (tem intermittent arm). All pts received 2.5 mg letrozole daily. Results: Initially, tem doses were 25 mg daily and 75 mg intermittent but were amended to 10 mg daily and 30 mg intermittent because 10 of 12 pts had dose delays, reductions, or discontinuations. Data collected by 15 Nov 2004 are presented for the 92 pts enrolled after the amendment (tem daily: 33; tem intermittent: 30; letrozole alone: 29). Grade 1–4 toxicities, regardless of causality, that occurred in >30% of pts included 10 mg daily: asthenia (45%), mucositis (42%), peripheral edema (36%); 30 mg intermittent: asthenia (63%), mucositis (57%), arthralgia (37%), anorexia (37%), diarrhea (33%), epistaxis (33%); letrozole alone: asthenia (52%), nausea (31%). Grade 3–4 toxicities, regardless of causality, that occurred in >5% of pts included 10 mg daily: hyperglycemia (9%); 30 mg intermittent: hyperglycemia (17%), asthenia (7%), hypertension (7%), hypokalemia (7%); letrozole alone: none. Objective responses (RECIST) occurred, 10 mg daily: 9 PR; 30 mg intermittent: 1 CR, 8 PR; letrozole alone: 2 CR, 10 PR. Clinical benefit (CR + PR + SD ≥8 wks) was 82%, 83%, and 79%, respectively. Progressive disease occurred at ≤8 wks in 12%, 10%, and 14% of pts, respectively. Progression-free survival (PFS) at 1 yr was estimated to be 69%, 62%, and 48%, respectively. Median PFS has been reached for the letrozole alone arm (9.2 mo) but not for the combination arms. Conclusions: Letrozole with 10 mg daily or 30 mg intermittent temsirolimus showed tolerability and clinical activity. Early data suggest that PFS may be longer for the combination arms than for the letrozole alone arm. An actively recruiting phase 3 study is being conducted. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth Wyeth Wyeth
Carpenter et al. (Wed,) studied this question.