TEAM RESULTS PUBLISHED-A TREND TOWARD INFERIORITY FROM OTHERS AI?

January 18, 2011 — Exemestane used alone for 5 years is similar to exemestane used after 2 to 3 years of tamoxifen in the prevention of relapse in postmenopausal women with hormone-responsive early breast cancer. This is the conclusion from the huge Tamoxifen Exemestane Adjuvant Multinational (TEAM) study, published online today in the Lancet.

The TEAM results have already been presented at major meetings, and have been discussed in some detail, as previously reported by Medscape Medical News.

Currently, exemestane is approved for use only after 2 to 3 years of tamoxifen.

The results from the TEAM study show that exemestane can either follow tamoxifen or be used alone for 5 years and achieve similar outcomes.

Both approaches can be considered appropriate options for postmenopausal women with hormone-receptor-positive early breast cancer, conclude the study investigators, led by Cornelius van de Velde, MD, PhD, from Leiden University Medical Center, the Netherlands.

They note, however, that the 2 approaches had different adverse-event profiles. Hence, they add, "consideration of the safety of these treatment strategies might play an important part in treatment decisions."

Benefit Similar, Adverse Effects Different

The TEAM study involved 9779 postmenopausal women with hormone-receptor-positive breast cancer who were randomized to either exemestane alone or tamoxifen for 2.5 to 3.0 years and then to exemestane.

The primary end point was disease-free survival at 5 years, which was similar in the 2 groups — 86% for exemestane alone and 85% for sequential tamoxifen and exemestane.

However, the adverse events reported were different for the 2 groups.

In the safety analysis, sequential treatment was associated with a higher incidence of gynecological symptoms (20% vs 11%), venous thrombosis (2% vs 1%), and endometrial abnormalities/thickening (4% vs <1%) than exemestane alone. In the group taking exemestane alone, there was a higher incidence of musculoskeletal adverse events (50% vs 44%), high blood pressure (6% vs 5%), and abnormal blood lipids (5% vs 3%).

Different From Other AIs?

Exemestane is 1 of 3 aromatase inhibitors (AIs) currently on the market for use in postmenopausal breast cancer, and is slightly different to the other 2. Exemestane is a steroidal product that binds irreversibly to the estrogen receptor, whereas letrozole (Femara, Novartis) and anastrozole (Arimidex, AstraZeneca) are both nonsteroidal and are reversible inhibitors.

There have also been a few differences in the clinical data. In discussing the TEAM results in the past with Medscape Medical News, Kimberly Blackwell, MD, from Duke University in Durham, North Carolina, noted: "Exemestane does appear to be different from letrozole and anastrozole in [that it has] a less documented benefit when used immediately after diagnosis."

Both letrozole and anastrozole have shown an improvement in progression-free survival, compared with tamoxifen used as monotherapy immediately after diagnosis; these data have led to the notion that letrozole and anastrozole are superior to tamoxifen, she noted. "We do not have that data for exemestane," she said. The first part of the TEAM trial compares exemestane with tamoxifen as monotherapy after diagnosis, and no difference was seen between the 2 groups, she pointed out.

However, TEAM investigator Elysee Hille, PhD, from Leiden University Medical Center, told Medscape Medical News that these trials are not comparable. The studies that showed AIs to be superior to tamoxifen were comparing 5 years of tamoxifen with 5 years of letrozole or anastrozole, she said. In the TEAM study, the patients on tamoxifen switched to exemestane after 2 to 3 years; "this is incomparable with the tamoxifen arm in the monotherapy trials," she said.

Dr. Hille also noted that, at some point early on in the TEAM study, there were preliminary plans to apply for an extension of the indication that is approved for exemestane. However, the patent expires this year, she said.

Anastrozole is already off patent in the United States and available in cheap generic versions, and letrozole is due to come off patent in the United States this year.

The TEAM study was funded by Pfizer, the manufacturer of exemestane. Dr. van de Velde and Dr. Hille have disclosed no relevant financial relationships, but several of their coauthors report receiving honoraria from Pfizer and other companies, and 1 coauthor is a Pfizer employee. Dr. Blackwell reports receiving honoraria from Genentech and GlaxoSmithKline, and consulting for Genentech.

Lancet. Published online January 18, 2011.