Top Line: Women with historically categorized intermediate risk Oncotype recurrence score (ORS=11-25) are currently risk-stratified based on age per TAILORx.
The Study: As we know, ORS was developed to convey expected benefit with more traditional cytotoxic chemotherapy. So what does that leave out of a more sophisticated equation? Expected benefit with the default treatment, endocrine therapy. The interesting German phase 3 ADAPT trial aimed to remedy that and is both huge and complicated. While the degree of estrogen receptor positivity has been linked to endocrine therapy response, these investigators took a more direct approach, relying on pathologic response to short-course neoadjuvant endocrine therapy. This publication pertains to the enrollees with ER+ HER2- cN0 breast cancer with an ORS 0-25 who received upfront endocrine therapy (typically tamoxifen if premenopausal and aromatase inhibitor if postmenopausal) for 3 weeks prior to surgery. Those with an ORS 0-11 received standard of care adjuvant endocrine therapy alone (n=868) and served as the control arm. Things get interesting in the group with an ORS 11-25. Those with surgical specimens with a Ki67 ≤10% were deemed endocrine therapy responders and also received endocrine therapy alone, regardless of age (n=1422)–serving as the experimental arm in this report. The others with an ORS 11-25 with a Ki67 >10% received chemo and are not discussed in this publication. The primary endpoint of noninferiority of invasive disease free survival at 5 years was established: 94% among those with ORS 0-11 and 93% among those with ORS 12-25 and Ki67 ≤10%. As expected, response to endocrine therapy was much more common among postmenopausal (78%) than premenopausal (41%), which may denote that our current treatment algorithm bifurcated by age 50 is a simple surrogate for this pattern. A final note is, using this approach, adding ovarian suppression to preop endocrine therapy will likely give premenopausal women their best shot at safely omitting chemo.
TBL: “For premenopausal patients with pN0-1, ADAPT suggests that those with RS0-11 do well on endocrine therapy [alone] and that short preoperative endocrine therapy is able to select those with RS12-25 who have excellent outcome on endocrine therapy alone.” | Nitz, J Clin Oncol 2022