medwireNews: Adding ovarian suppression to tamoxifen significantly improves disease-free survival (DFS) over tamoxifen alone in premenopausal women with hormone receptor-positive breast cancer, the latest data from the SOFT and TEXT trials show.
The findings also indicated even greater improvements when ovarian suppression was added to exemestane, which makes “this combination worthy of use in clinical practice,” say Prudence Francis (Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia) and co-investigators.
The updated results, analyzed after a median 8 and 9 years of follow-up for SOFT and TEXT respectively, were simultaneously published in The New England Journal of Medicine and presented at the ASCO Annual Meeting 2018 in Chicago, Illinois, USA.
In SOFT, the risk for disease recurrence or death was a significant 24% lower in patients treated for 5 years with tamoxifen plus ovarian suppression (n=1015) and 35% lower in those treated with exemestane plus ovarian suppression (n=1014) compared with patients who received tamoxifen alone (n=1018).
The corresponding 8-year DFS rates were 83.2%, 85.9%, and 78.9%.
These findings differ from the initial analysis of SOFT data that showed the addition of ovarian suppression to adjuvant tamoxifen did not significantly improve DFS after a median follow-up of 5.6 years.
Overall survival (OS) was also significantly better at 8 years in the women who received tamoxifen plus ovarian suppression than in those who received tamoxifen alone, at 93.3% versus 91.5% (hazard ratio=0.67), but not in those who received exemestane plus ovarian suppression, at 92.1%.
When the data for the two studies were combined, comprising 4690 patients, DFS was significantly better with exemestane plus ovarian suppression than with tamoxifen plus ovarian suppression (86.8 vs 82.8%) but OS was similar between the two groups (93.4 vs 93.3%).
The results were similar for the majority of subgroups analyzed, with the exception of HER2 status. Specifically, women with HER-2 positive disease derived significantly greater benefit from the addition of tamoxifen to ovarian suppression and less benefit from the addition of exemestane than did those with HER2-negative disease.
Ovarian suppression was also associated with a higher rate of grade 3 or worse adverse events, including osteoporosis.
Discussing the side effects of ovarian suppression in an editorial accompanying the publication, Marc Lippman, from the University of Miami Miller School of Medicine in Florida, USA, says that it “is unfortunate that the use of bone-strengthening agents (e.g., bisphosphonates) or inhibitors of receptor activator of nuclear factor-κB ligand (RANKL) was not permitted in this trial unless such use was medically indicated.”
However, he believes that the findings “will encourage physicians to attempt the more effective therapy and manage side effects if they occur.”
He adds: “In our view, the data strongly favor adding either a bisphosphonate or RANKL inhibitor administered at 6-month intervals for 3 years to help prevent problems with loss of bone density and increase survival in such patients.”
By Laura Cowen
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