ATLANTA — Switching from tamoxifen to aromatase inhibitors improved overall survival for 8,794 breast cancer patients in four randomized phase III trials, according to a pooled analysis presented at the annual meeting of the American Society of Clinical Oncology.
Despite reporting benefits in progression-free survival, none of the individual published trials had shown that significantly more patients lived if they were switched to an individual aromatase inhibitor after 2–3 years of adjuvant hormonal therapy with tamoxifen.
Dr. Emilio Bria of Italy's Regina Elena National Cancer Institute in Rome and his coinvestigators found an absolute overall survival gain of 1.2% with aromatase inhibitors in the pooled data. They translated this into 100 patients who were cured as a result of the substitution. Patients switched to an aromatase inhibitor had a relative risk of 0.76 for death from any cause, compared with patients who continued on tamoxifen.
“We were looking not for the effect of a single drug, but the effect of a class of drugs,” Dr. Bria said in an interview alongside the poster, where he was joined by the lead author, Dr. Mariangela Ciccarese. “We found there is a benefit in survival when you pool all the results.”
The pooled analysis only addressed an early-switch strategy, as Dr. Bria said he could not find enough trials that have so far reported outcomes for up-front hormonal therapy with an aromatase inhibitor or for late switching to an aromatase inhibitor. He said he hopes to pool additional studies and compare early, up-front, and late strategies when more trials become available.
The pooled trials compared continued tamoxifen use to initial tamoxifen followed by aminoglutethimide, exemestane, or anastrozole (J. Clin. Oncol. 2001;19:4209–15, N. Engl. J. Med. 2004;350:1081–92, J. Clin. Oncol. 2005;23:5138–47, Lancet 2005;366: 455–62).
Other highly significant findings in the pooled analyses included a relative risk ratio of 0.67 for any event (local or distant relapse, secondary breast cancer, or death from any cause) in the aromatase inhibitor group. The relative risk of distant recurrence was 0.65 with aromatase inhibitors, with an absolute benefit of 2.4% and a need-to-treat estimate of 43 patients to prevent one death.
Patients switched to aromatase inhibitors were significantly more likely than patients who continued on tamoxifen to have fractures and musculoskeletal pain. The relative risk ratios were 1.50 and 1.33, respectively. Cardiovascular events also increased slightly, with a relative risk ratio of 1.22.
In looking for the effect of the whole class of drugs, 'we found there is a benefit in survival when you pool all the results.' DR. BRIA