Breast Ca Survival Aided by Early Switch to Aromatase Inhibitor

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.

The pooled analysis only addressed an early-switch strategy because, 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. 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, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) 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. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA

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.

The pooled analysis only addressed an early-switch strategy because, 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. 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, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) 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. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA

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.

The pooled analysis only addressed an early-switch strategy because, 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. 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, with an absolute benefit of 3.8% and a need-to-treat estimate of 26 patients to prevent one event.

The relative risk of recurrence was 0.68 with aromatase inhibitors, with an absolute benefit of 2.8% and a need-to-treat estimate of 36 patients.

For late recurrence, the relative risk was 0.64 and the absolute benefit was less than 1% with a need-to-treat estimate of 170 patients to prevent one death. (This was based on pooled data from 8,413 patients in three trials.) 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. Patients on aromatase inhibitors were, however, significantly less likely to have endometrial cancer (relative risk ratio 0.32) and somewhat less likely to have thromboembolic events (relative risk ratio 0.73).

'We were looking not for the effect of a single drug, but the effect of a class of drugs.' DR. BRIA