Chemotherapy May Be Safely Withheld for Breast Cancer Patients with 21-gene Recurrence Scores Under 26
TAILORx trial presented at ASCO and simultaneously published in NEJM (June 3, 2018).
Joseph Sparano M.D. presented the long awaited results of the TAILORx study Sunday, June 3 at the ASCO meeting in Chicago.
Study protocol: 6,711 Patients with Oncotype DX scores from 11-25 were randomized to Chemotherapy followed by Endocrine Therapy vs Endocrine Therapy alone.
Results: No difference in overall survival (and other survivals – local regional, distant and invasive disease-free) between the two groups.
Take Home: Chemotherapy can be safely withheld for the majority of women with Risk Scores 25 and under.
Caveats: 1) Intermediate Risk Group was modified from the original Intermediate Risk Group 18-31 to 11-25. So what do we do with the Intermediate Risk Score patients from 26-31? According to Steve Shak M.D. of Genomic Health, “other data the company has amassed over the years illustrates that there is steadily increasing benefit from chemo as RS increases from 25 to 30. Benefit might not be as great in that subgroup as it is for those with scores over 31, but it's enough to support shifting to a binary cutoff at the TAILORx-defined RS 25”.
2) There was some distant disease-free survival benefit (NOT overall survival) for women <50 receiving chemotherapy and endocrine therapy (+1.6% at 9 years for RS 16-20; +6.5% at 9 years for RS 21-25). This has led most commentators so far to suggest a cutoff at a RS > 15 may be best for women under 50. This hasty generalization would necessarily lead to unnecessary chemotherapy for almost half of the women in this group; 46% of women under 50 had a score of 16-25. A more thoughtful analysis, suggested by Lisa Carey, M.D., commenting on the study at ASCO, is that this benefit is most likely due to the fact that chemotherapy induces menopause in most premenopausal breast cancer patients. Addressing this suggestion in the NEJM article the authors state: “A greater treatment effect from adjuvant chemotherapy has been noted in younger women, which may be at least partly explained by an antiestrogenic effect associated with premature menopause induced by chemotherapy. We did not collect data on chemotherapy-induced menopause. It remains unclear whether similar benefits could be achieved with ovarian suppression plus an aromatase inhibitor instead of chemotherapy”.
Data from the NEJM article Supplementary Appendix show that no benefit occurred if women were post-menopausal when entering the trial whereas premenopausal RS 16-25 women show an identical trend towards benefit. This interpretation is supported by data from the SOFT and TEXT trials wherein premenopausal women at intermediate or high risk have substantial improvement in outcome with ovarian function suppression, as well as older studies demonstrating better outcomes for premenopausal women who became amenorrheic after chemotherapy. Much more on this topic in the future.